Bio


Dr. Thong is a surgeon specializing in urologic oncology. He has expertise in all aspects of prostate, kidney, bladder, and testicular cancer care, including endoscopic, robotic, and open surgery, and has a special interest in complex cases including: salvage surgery following radiation or chemotherapy, resection of locally advanced tumors, minimal access robotic surgery, and MRI-US fusion targeted biopsies. Dr. Thong is the first surgeon in northern California to utilize single port robotic assisted laparoscopic technology for both pelvic and retroperitoneal surgeries. He has won numerous awards including the NIH Ruth L. Kirschstein National Research Service Award, and has authored and co-authored publications on the treatment of urologic cancers.

Clinical Focus


  • Urologic oncology
  • Urology
  • Value-Based Health Insurance

Academic Appointments


Boards, Advisory Committees, Professional Organizations


  • Active member, Society of Urologic Oncology (2015 - Present)
  • Member, American Society of Clinical Oncology (2015 - Present)
  • Associate member, American Urological Association (2010 - Present)
  • Member, American Medical Association (2008 - Present)

Professional Education


  • AB, Princeton University (2004)
  • MD, University of Chicago, Pritzker School of Medicine (2008)
  • Residency, Stanford University (2014)
  • Fellowship, Memorial Sloan Kettering Cancer Center (2016)
  • MPH, Harvard University (2016)
  • Board Certification: American Board of Urology, Urology (2018)

Graduate and Fellowship Programs


  • Oncology (Fellowship Program)

All Publications


  • A Pilot Study of 68Ga-PSMA11 and 68Ga-RM2 PET/MRI for Biopsy Guidance in Patients with Suspected Prostate Cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Duan, H., Ghanouni, P., Daniel, B., Rosenberg, J., Thong, A., Kunder, C., Mari Aparici, C., Davidzon, G. A., Moradi, F., Sonn, G. A., Iagaru, A. 2022

    Abstract

    Purpose: Targeting of lesions seen on multiparametric MRI (mpMRI) improves prostate cancer (PC) detection at biopsy. However, 20-65% of highly suspicious lesions on mpMRI (PI-RADS 4 or 5) are false positives (FP), while 5-10% of clinically significant PC (csPC) are missed. Prostate specific membrane antigen (PSMA) and gastrin-releasing peptide receptors (GRPR) are both overexpressed in PC. We therefore aimed to evaluate the potential of 68Ga-PSMA11 and 68Ga-RM2 PET/MRI for biopsy guidance in patients with suspected PC. Methods: A highly selective cohort of 13 men, aged 58.0±7.1 years, with suspected PC (persistently high prostate-specific antigen [PSA] and PSA density) but negative or equivocal mpMRI and/or negative biopsy were prospectively enrolled to undergo 68Ga-PSMA11 and 68Ga-RM2 PET/MRI. PET/MRI included whole-body and dedicated pelvic imaging after a delay of 20 minutes. All patients had targeted biopsy of any lesions seen on PET followed by standard 12-core biopsy. Maximum standardized uptake values (SUVmax) of suspected PC lesions were collected and compared to gold standard biopsy. Results: PSA and PSA density at enrollment were 9.8±6.0 (1.5-25.5) ng/mL and 0.20±0.18 (0.06-0.68) ng/mL2, respectively. Standardized systematic biopsy revealed a total of 14 PC in 8 participants: 7 were csPC and 7 were non-clinically significant PC (ncsPC). 68Ga-PSMA11 identified 25 lesions, of which 11 (44%) were true positive (TP) (5 csPC). 68Ga-RM2 showed 27 lesions, of which 14 (52%) were TP, identifying all 7 csPC and also 7 ncsPC. There were 17 concordant lesions in 11 patients vs. 14 discordant lesions in 7 patients between 68Ga-PSMA11 and 68Ga-RM2 PET. Incongruent lesions had the highest rate of FP (12 FP vs. 2 TP). SUVmax was significantly higher for TP than FP lesions in delayed pelvic imaging for 68Ga-PSMA11 (6.49±4.14 vs. 4.05±1.55, P = 0.023) but not for whole-body images, nor for 68Ga-RM2. Conclusion: Our results show that 68Ga-PSMA11 and 68Ga-RM2 PET/MRI are feasible for biopsy guidance in suspected PC. Both radiopharmaceuticals detected additional clinically significant cancers not seen on mpMRI in this selective cohort. 68Ga-RM2 PET/MRI identified all csPC confirmed at biopsy.

    View details for DOI 10.2967/jnumed.122.264448

    View details for PubMedID 36396456

  • A Pilot Study of Ga-68-PSMA11 and Ga-68-RM2 PET/MRI for Evaluation of Prostate Cancer Response to High Intensity Focused Ultrasound (HIFU) Therapy Duan, H., Ghanouni, P., Daniel, B., Rosenberg, J., Davidzon, G. A., Aparici, C., Thong, A., Sonn, G. A., Kunder, C., Iagaru, A. SPRINGER. 2022: S497-S498
  • A Pilot Study of Ga-68-PSMA11 and 68Ga-RM2 PET/MRI for Biopsy Guidance in Patients with Suspected Prostate Cancer Duan, H., Ghanouni, P., Daniel, B., Rosenberg, J., Thong, A., Sonn, G. A., Kunder, C., Davidzon, G. A., Aparici, C., Moradi, F., Iagaru, A. SPRINGER. 2022: S484
  • Correlation of 68Ga-RM2 PET with Post-Surgery Histopathology Findings in Patients with Newly Diagnosed Intermediate- or High-Risk Prostate Cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Duan, H., Baratto, L., Fan, R. E., Soerensen, S. J., Liang, T., Chung, B. I., Thong, A. E., Gill, H., Kunder, C., Stoyanova, T., Rusu, M., Loening, A. M., Ghanouni, P., Davidzon, G. A., Moradi, F., Sonn, G. A., Iagaru, A. 2022

    Abstract

    Rationale: 68Ga-RM2 targets gastrin-releasing peptide receptors (GRPR), which are overexpressed in prostate cancer (PC). Here, we compared pre-operative 68Ga-RM2 PET to post-surgery histopathology in patients with newly diagnosed intermediate- or high-risk PC. Methods: Forty-one men, 64.0+/-6.7-year-old, were prospectively enrolled. PET images were acquired 42 - 72 (median+/-SD 52.5+/-6.5) minutes after injection of 118.4 - 247.9 (median+/-SD 138.0+/-22.2)MBq of 68Ga-RM2. PET findings were compared to pre-operative mpMRI (n = 36) and 68Ga-PSMA11 PET (n = 17) and correlated to post-prostatectomy whole-mount histopathology (n = 32) and time to biochemical recurrence. Nine participants decided to undergo radiation therapy after study enrollment. Results: All participants had intermediate (n = 17) or high-risk (n = 24) PC and were scheduled for prostatectomy. Prostate specific antigen (PSA) was 8.8+/-77.4 (range 2.5 - 504) ng/mL, and 7.6+/-5.3 (range 2.5 - 28.0) ng/mL when excluding participants who ultimately underwent radiation treatment. Pre-operative 68Ga-RM2 PET identified 70 intraprostatic foci of uptake in 40/41 patients. Post-prostatectomy histopathology was available in 32 patients in which 68Ga-RM2 PET identified 50/54 intraprostatic lesions (detection rate = 93%). 68Ga-RM2 uptake was recorded in 19 non-enlarged pelvic lymph nodes in 6 patients. Pathology confirmed lymph node metastases in 16 lesions, and follow-up imaging confirmed nodal metastases in 2 lesions. 68Ga-PSMA11 and 68Ga-RM2 PET identified 27 and 26 intraprostatic lesions, respectively, and 5 pelvic lymph nodes each in 17 patients. Concordance between 68Ga-RM2 and 68Ga-PSMA11 PET was found in 18 prostatic lesions in 11 patients, and 4 lymph nodes in 2 patients. Non-congruent findings were observed in 6 patients (intraprostatic lesions in 4 patients and nodal lesions in 2 patients). Both 68Ga-RM2 and 68Ga-PSMA11 had higher sensitivity and accuracy rates with 98%, 89%, and 95%, 89%, respectively, compared to mpMRI at 77% and 77%. Specificity was highest for mpMRI with 75% followed by 68Ga-PSMA11 (67%), and 68Ga-RM2 (65%). Conclusion: 68Ga-RM2 PET accurately detects intermediate- and high-risk primary PC with a detection rate of 93%. In addition, it showed significantly higher specificity and accuracy compared to mpMRI and similar performance to 68Ga-PSMA11 PET. These findings need to be confirmed in larger studies to identify which patients will benefit from one or the other or both radiopharmaceuticals.

    View details for DOI 10.2967/jnumed.122.263971

    View details for PubMedID 35552245

  • 68Ga-PSMA-11 PET/MRI in patients with newly diagnosed intermediate or high-risk prostate adenocarcinoma: PET findings correlate with outcomes after definitive treatment. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Moradi, F., Duan, H., Song, H., Davidzon, G. A., Chung, B. I., Thong, A. E., Loening, A. M., Ghanouni, P., Sonn, G., Iagaru, A. 2022

    Abstract

    Prostate-specific membrane antigen (PSMA) PET offers superior accuracy to other imaging modalities in initial staging of prostate cancer and is more likely to affect management. We examined the prognostic value of 68Ga-PSMA-11 uptake in primary lesion and presence of metastatic disease on PET in newly diagnosed prostate cancer patients prior to initial therapy. Methods: In a prospective study from April 2016 to December 2020, 68Ga-PSMA-11 PET/MRI was done in men with new diagnosis of intermediate or high-grade prostate cancer who were candidates for prostatectomy. Patients were followed up after initial therapy for up to 5 years. We examined the Kendall correlation between PET (intense uptake in primary lesion and presence of metastatic disease) and clinical and pathologic findings (grade group, extraprostatic extension, nodal involvement) relevant for risk stratification, and examined the relationship between PET findings and outcome using Kaplan-Meier analysis. Results: Seventy-three men, 64.0±6.3 years of age were imaged. Seventy-two had focal uptake in prostate and in 20 (27%), PSMA-avid metastatic disease was identified. Uptake correlated with grade group and prostate-specific antigen (PSA). Presence of PSMA metastasis correlated with grade group and pathologic nodal stage. PSMA PET had higher per-patients positivity than nodal dissection in patients with only 5-15 nodes removed (8/41 vs. 3/41) but lower positivity if more than 15 nodes were removed (13/21 vs. 10/21). High uptake in primary (SUVmax>12.5, P = .008) and presence of PSMA metastasis (P = .013) were associated with biochemical failure, and corresponding hazard ratios for recurrence within 2-years (4.93 and 3.95, respectively) were similar or higher than other clinicopathologic prognostic factors. Conclusions: 68Ga-PSMA-11 PET can risk stratify patients with intermediate or high-grade prostate cancer prior to prostatectomy based on degree of uptake in prostate and presence of metastatic disease.

    View details for DOI 10.2967/jnumed.122.263897

    View details for PubMedID 35512996

  • Renal Morbidity Following Radical Cystectomy in Patients with Bladder Cancer. European urology open science Schmidt, B., Velaer, K. N., Thomas, I., Ganesan, C., Song, S., Pao, A. C., Thong, A. E., Liao, J. C., Chertow, G. M., Skinner, E. C., Leppert, J. T. 1800; 35: 29-36

    Abstract

    Background: Patients with chronic kidney disease (CKD) are poor candidates for standard treatments for muscle-invasive bladder cancer (MIBC) and may be more likely to experience adverse outcomes when diagnosed with MIBC.Objective: To investigate factors associated with the development of advanced CKD following radical cystectomy.Design setting and participants: Using national Veterans Health Administration utilization files, we identified 3360 patients who underwent radical cystectomy for MIBC between 2004 and 2018.Outcome measurements and statistical analysis: We examined factors associated with the development of advanced CKD (estimated glomerular filtration rate [eGFR] of <30 ml/min/1.73 m2) after radical cystectomy using multivariable logistic and proportional hazard regression, with and without consideration of competing risks. We examined survival using Kaplan-Meier product limit estimates and proportional hazard regression.Results and limitations: The median age at surgery was 67 yr and the mean preoperative eGFR was 69.1 ± 20.3 ml/min/1.73 m2. Approximately three out of ten patients (n = 962, 29%) progressed to advanced CKD within 12 mo. Older age (hazard ratio [HR] per 5-yr increase 1.15, 95% confidence interval [CI] 1.10-1.20), preoperative hydronephrosis (HR 1.50, 95% CI 1.29-1.76), adjuvant chemotherapy (HR 1.19, 95% CI 1.00-1.41), higher comorbidity index (HR 1.13, 95% CI 1.11-1.16 per point), and lower baseline kidney function (HR 0.75, 95% CI 0.73-0.78) were associated with the development of advanced CKD. Baseline kidney function at the time of surgery was associated with survival. Generalizability is limited due to the predominantly male cohort.Conclusions: Impaired kidney function at baseline is associated with progression to advanced CKD and mortality after radical cystectomy. Preoperative kidney function should be incorporated into risk stratification algorithms for patients undergoing radical cystectomy.Patient summary: Impaired kidney function at baseline is associated with progression to advanced chronic kidney disease and mortality after radical cystectomy.

    View details for DOI 10.1016/j.euros.2021.11.001

    View details for PubMedID 35024629

  • A Pilot Study of Ga-68-PSMA11 and Ga-68-RM2 PET/MRI for Evaluation of Prostate Cancer Response to High Intensity Focused Ultrasound (HIFU) Therapy Duan, H., Ghanouni, P., Hatami, N., Davidzon, G. A., Aparici, C., Thong, A., Sonn, G. A., Iagaru, A. SPRINGER. 2021: S205-S206
  • A Pilot Study of 68Ga-PSMA11 and 68Ga-RM2 PET/MRI for Biopsy Guidance in Patients with Suspected Prostate Cancer Duan, H., Ferri, V., Ghanouni, P., Daniel, B., Hatami, N., Davidzon, G. A., Aparici, C., Thong, A., Sonn, G. A., Iagaru, A. SPRINGER. 2021: S204
  • The stanford prostate cancer calculator: Development and external validation of online nomograms incorporating PIRADS scores to predict clinically significant prostate cancer. Urologic oncology Wang, N. N., Zhou, S. R., Chen, L., Tibshirani, R., Fan, R. E., Ghanouni, P., Thong, A. E., To'o, K. J., Amirkhiz, K., Nix, J. W., Gordetsky, J. B., Sprenkle, P., Rais-Bahrami, S., Sonn, G. A. 2021

    Abstract

    BACKGROUND: While multiparametric MRI (mpMRI) has high sensitivity for detection of clinically significant prostate cancer (CSC), false positives and negatives remain common. Calculators that combine mpMRI with clinical variables can improve cancer risk assessment, while providing more accurate predictions for individual patients. We sought to create and externally validate nomograms incorporating Prostate Imaging Reporting and Data System (PIRADS) scores and clinical data to predict the presence of CSC in men of all biopsy backgrounds.METHODS: Data from 2125 men undergoing mpMRI and MR fusion biopsy from 2014 to 2018 at Stanford, Yale, and UAB were prospectively collected. Clinical data included age, race, PSA, biopsy status, PIRADS scores, and prostate volume. A nomogram predicting detection of CSC on targeted or systematic biopsy was created.RESULTS: Biopsy history, Prostate Specific Antigen (PSA) density, PIRADS score of 4 or 5, Caucasian race, and age were significant independent predictors. Our nomogram-the Stanford Prostate Cancer Calculator (SPCC)-combined these factors in a logistic regression to provide stronger predictive accuracy than PSA density or PIRADS alone. Validation of the SPCC using data from Yale and UAB yielded robust AUC values.CONCLUSIONS: The SPCC combines pre-biopsy mpMRI with clinical data to more accurately predict the probability of CSC in men of all biopsy backgrounds. The SPCC demonstrates strong external generalizability with successful validation in two separate institutions. The calculator is available as a free web-based tool that can direct real-time clinical decision-making.

    View details for DOI 10.1016/j.urolonc.2021.06.004

    View details for PubMedID 34247909

  • A Pilot Study of68Ga-PSMA11 PET/MRI and68GaRM2 PET/MRI for Biopsy Guidance in Patients with Suspected Prostate Cancer Duan, H., Ferri, V., Ghanouni, P., Daniel, B., Hatami, N., Davidzon, G., Aparici, C., Moradi, F., Thong, A., Sonn, G., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2021
  • Bupivacaine local anesthetic to decrease opioid requirements after radical cystectomy: Does formulation matter? Urologic oncology Schmidt, B. n., Bhambhvani, H. P., Greenberg, D. R., Prado, K. n., Shafer, S. n., Thong, A. n., Gill, H. n., Skinner, E. n., Shah, J. B. 2020

    Abstract

    Reduction of opioids is an important goal in the care of patients undergoing radical cystectomy (RC). Liposomal bupivacaine (LB) has been shown to be a safe and effective pain reliever in the immediate postoperative period and has been reported to reduce postoperative opioid requirements. Since the liposomal formulation is predicated on slow systemic absorption, the amount of bupivacaine administered is notably higher than that typically used with standard bupivacaine (SB) formulations. In addition, LB is costly, not universally available, and studies comparing this formulation to SB are lacking. We sought to determine if there is a difference in postoperative opioid requirements in patients who receive LB vs. high dose SB at the time of RC.In May 2019 we transitioned to administration of high-volume SB injected intraoperatively at the time of RC. This prospective cohort was compared to a historical cohort of patients who received injection of LB at the time of surgery. Primary endpoints included postsurgical opioid use measured in morphine equivalent dose (MED) and patient-reported Numeric Rating Scale (NRS) pain scores and length of stay. All patients were managed using principles of enhanced recovery after surgery (ERAS).From May 2019 through August 2019, 28 patients underwent RC and met eligibility criteria to receive SB at the time of surgery. They were compared to a historical cohort of 34 patients who received LB between November 2017 and July 2018. There was no difference in MED exposure either in the postanesthesia care unit (SB 9.0 ± 8.9 MED vs. LB 6.5 ± 9.4 MED, P= 0.29) or during the remainder of the hospital stay (SB 36.8 ± 56.9 MED vs. LB 42.1 ± 102.5 MED, P= 0.81), no difference in NRS pain scores on postoperative day 1 (SB 2.6 ± 1.6 vs. LB 2.1 ± 1.7, P= 0.23), day 2 (SB 2.4 ± 1.8 vs. LB 1.9 ± 1.6, P= 0.19), or day 3 (SB 1.9 ± 1.8 vs. LB 1.7 ± 1.7, P= 0.69) and no difference in length of stay (SB 5.0 ± 1.7 days, LB 4.9 ± 3.3 days, P= 0.93). Subgroup analysis of open RC and robotic-assisted RC showed no significant difference in MED or pain scores between LB and SB patients.Among patients undergoing RC under ERAS protocol there was no significant difference in postoperative opioid consumption, NRS pain scores, or length of stay among patients receiving SB compared to LB.

    View details for DOI 10.1016/j.urolonc.2020.11.008

    View details for PubMedID 33303378

  • Is A Systematic Transrectal Ultrasound-Guided Biopsy Required When a Targeted Magnetic Resonance Imaging-Ultrasound Fusion Biopsy is Performed? Bagshaw, H. P., Sonn, G. A., Fan, R. E., Ghanouni, P., Loening, A. M., Heidari, N., Von Eyben, R., Thong, A. E., Buyyounouski, M. K. ELSEVIER SCIENCE INC. 2019: E262
  • Prostate Magnetic Resonance Imaging Interpretation Varies Substantially Across Radiologists EUROPEAN UROLOGY FOCUS Sonn, G. A., Fan, R. E., Ghanouni, P., Wang, N. N., Brooks, J. D., Loening, A. M., Daniel, B. L., To'o, K. J., Thong, A. E., Leppert, J. T. 2019; 5 (4): 592–99
  • AUTOMATED DETECTION OF PROSTATE CANCER ON MULTIPARAMETRIC MRI USING DEEP NEURAL NETWORKS TRAINED ON SPATIAL COORDINATES AND PATHOLOGY OF BIOPSY CORES Chen, L., Bien, N., Fan, R., Cheong, R., Rajpurkar, P., Thong, A., Wang, N., Ahmadi, S., Rusu, M., Brooks, J., Ng, A., Sonn, G. LIPPINCOTT WILLIAMS & WILKINS. 2019: E1098
  • Concordance between patient-reported and physician-reported sexual function after radical prostatectomy. Urologic oncology Thong, A. E., Ying Poon, B., Lee, J. K., Vertosick, E., Sjoberg, D. D., Vickers, A. J., Ehdaie, B. 2017

    Abstract

    Accurately tracking health-related quality-of-life after radical prostatectomy is critical to counseling patients and improving technique. Physicians consistently overestimate functional recovery. We measured concordance between surgeon-assessed and patient-reported outcomes and evaluated a novel method to provide feedback to surgeons.Men treated with radical prostatectomy self-completed the International Index of Erectile Function-6 questionnaire at each postoperative visit. Separately, physicians graded sexual function on a 5-point scale. International Index of Erectile Function -6 score<22 and grade ≥3 defined patient-reported and physician-assessed erectile dysfunction (ED), respectively. Feedback on concordance was given to physicians starting in May 2013 with the implementation of the Amplio feedback system. Chi-square tests were used to assess agreement proportions and linear regression to evaluate changes in agreement after implementation.From 2009 to 2015, 3,053 men completed at least 1 postprostatectomy questionnaire and had a concurrent independent physician-reported outcome. Prior to implementation of feedback in 2013, patients and physicians were consistent as to ED 83% of the time; in 10% of cases, physicians overestimated function; in 7% of cases, physicians, but not patients reported ED. Agreement increased after implementation of feedback but this was not statistically significant, likely owing to a ceiling effect. Supporting this hypothesis, increase in agreement postfeedback was greater during late follow-up (≥12mo), where baseline agreement was lower compared to earlier follow-up.Agreement was higher than expected at baseline; implementation of feedback regarding discrepancies between patient-reported and physician-assessed outcomes did not further improve agreement significantly. Our observed high rate of agreement may be partly attributed to our institutional practice of systematically capturing patient-reported outcomes as part of normal clinical care.

    View details for DOI 10.1016/j.urolonc.2017.09.017

    View details for PubMedID 29031420

  • Prostate Magnetic Resonance Imaging Interpretation Varies Substantially Across Radiologists. European urology focus Sonn, G. A., Fan, R. E., Ghanouni, P. n., Wang, N. N., Brooks, J. D., Loening, A. M., Daniel, B. L., To'o, K. J., Thong, A. E., Leppert, J. T. 2017

    Abstract

    Multiparametric magnetic resonance imaging (mpMRI) interpreted by experts is a powerful tool for diagnosing prostate cancer. However, the generalizability of published results across radiologists of varying expertise has not been verified.To assess variability in mpMRI reporting and diagnostic accuracy across radiologists of varying experience in routine clinical care.Men who underwent mpMRI and MR-fusion biopsy between 2014-2016. Each MRI scan was read by one of nine radiologists using the Prostate Imaging Reporting and Data System (PIRADS) and was not re-read before biopsy. Biopsy histopathology was the reference standard.Outcomes were the PIRADS score distribution and diagnostic accuracy across nine radiologists. We evaluated the association between age, prostate-specific antigen, PIRADS score, and radiologist in predicting clinically significant cancer (Gleason ≥7) using multivariable logistic regression. We conducted sensitivity analyses for case volume and changes in accuracy over time.We analyzed data for 409 subjects with 503 MRI lesions. While the number of lesions (mean 1.2 lesions/patient) did not differ across radiologists, substantial variation existed in PIRADS distribution and cancer yield. The significant cancer detection rate was 3-27% for PIRADS 3 lesions, 23-65% for PIRADS 4, and 40-80% for PIRADS 5 across radiologists. Some 13-60% of men with a PIRADS score of <3 on MRI harbored clinically significant cancer. The area under the receiver operating characteristic curve varied from 0.69 to 0.81 for detection of clinically significant cancer. PIRADS score (p<0.0001) and radiologist (p=0.042) were independently associated with cancer in multivariable analysis. Neither individual radiologist volume nor study period impacted the results. MRI scans were not retrospectively re-read by all radiologists, precluding measurement of inter-observer agreement.We observed considerable variability in PIRADS score assignment and significant cancer yield across radiologists. We advise internal evaluation of mpMRI accuracy before widespread adoption.We evaluated the interpretation of multiparametric magnetic resonance imaging of the prostate in routine clinical care. Diagnostic accuracy depends on the Prostate Imaging Reporting and Data System score and the radiologist.

    View details for PubMedID 29226826

  • Accuracy of Self-reported Smoking Exposure Among Bladder Cancer Patients Undergoing Surveillance at a Tertiary Referral Center. European urology focus Thong, A. E., Petruzella, S., Orlow, I., Zabor, E. C., Ehdaie, B., Ostroff, J. S., Bochner, B. H., Furberg Barnes, H. 2016; 2 (4): 441-444

    Abstract

    Smoking is a risk factor for developing bladder cancer (BCa). Even though continued exposure after diagnosis may adversely affect prognosis, patients may be reluctant to disclose to their physicians that they are currently smoking, leading to inaccurate reporting of exposure and missed opportunities to deliver smoking-cessation advice and treatment in the context of cancer care.We examined the extent of misclassification of recent smoking exposure among patients undergoing BCa surveillance.A consecutive sample of 145 patients with a self-reported smoking history and prior initial diagnosis of BCa was recruited from a tertiary referral urology clinic.Patients were asked if they had smoked a cigarette or used nicotine replacement therapy (NRT) within the past week and whether they lived with a smoker. At the same visit, we collected urine under a biospecimen protocol. We used urinary cotinine, the primary metabolite of nicotine, as an objective biomarker of recent smoking exposure. Nine patients whose urine could not be interpreted for cotinine were excluded. We calculated the smoking status misreporting rate by comparing biochemically verified smoking status (≥31.5 ng/ml vs <31.5 ng/ml) against self-reported current smoking status (yes vs no) while considering recent NRT use.Overall, 11% (15 of 136) of patients had cotinine values consistent with current smoking. Of these 15 patients, 7 reported being former smokers, resulting in a 47% misclassification rate. However, three of the seven patients who denied smoking in the past week were currently using NRT. Excluding NRT users, the misclassification rate was 33%.Future studies investigating the impact of postdiagnosis nicotine exposure on BCa outcomes should use biochemical verification combined with self-reported smoking exposure to classify patients accurately.Bladder cancer patients may misreport smoking exposure, thereby missing opportunities for smoking cessation.

    View details for DOI 10.1016/j.euf.2015.12.002

    View details for PubMedID 28723477

  • Comparative Effectiveness of Targeted Prostate Biopsy Using Magnetic Resonance Imaging Ultrasound Fusion Software and Visual Targeting: a Prospective Study. journal of urology Lee, D. J., Recabal, P., Sjoberg, D. D., Thong, A., Lee, J. K., Eastham, J. A., Scardino, P. T., Vargas, H. A., Coleman, J., Ehdaie, B. 2016; 196 (3): 697-702

    Abstract

    We compared the diagnostic outcomes of magnetic resonance-ultrasound fusion and visually targeted biopsy for targeting regions of interest on prostate multiparametric magnetic resonance imaging.Patients presenting for prostate biopsy with regions of interest on multiparametric magnetic resonance imaging underwent magnetic resonance imaging targeted biopsy. For each region of interest 2 visually targeted cores were obtained, followed by 2 cores using a magnetic resonance-ultrasound fusion device. Our primary end point was the difference in the detection of high grade (Gleason 7 or greater) and any grade cancer between visually targeted and magnetic resonance-ultrasound fusion, investigated using McNemar's method. Secondary end points were the difference in detection rate by biopsy location using a logistic regression model and the difference in median cancer length using the Wilcoxon signed rank test.We identified 396 regions of interest in 286 men. The difference in the detection of high grade cancer between magnetic resonance-ultrasound fusion biopsy and visually targeted biopsy was -1.4% (95% CI -6.4 to 3.6, p=0.6) and for any grade cancer the difference was 3.5% (95% CI -1.9 to 8.9, p=0.2). Median cancer length detected by magnetic resonance-ultrasound fusion and visually targeted biopsy was 5.5 vs 5.8 mm, respectively (p=0.8). Magnetic resonance-ultrasound fusion biopsy detected 15% more cancers in the transition zone (p=0.046) and visually targeted biopsy detected 11% more high grade cancer at the prostate base (p=0.005). Only 52% of all high grade cancers were detected by both techniques.We found no evidence of a significant difference in the detection of high grade or any grade cancer between visually targeted and magnetic resonance-ultrasound fusion biopsy. However, the performance of each technique varied in specific biopsy locations and the outcomes of both techniques were complementary. Combining visually targeted biopsy and magnetic resonance-ultrasound fusion biopsy may optimize the detection of prostate cancer.

    View details for DOI 10.1016/j.juro.2016.03.149

    View details for PubMedID 27038768

    View details for PubMedCentralID PMC5014662

  • Unexpected Long-term Improvements in Urinary and Erectile Function in a Large Cohort of Men with Self-reported Outcomes Following Radical Prostatectomy EUROPEAN UROLOGY Lee, J. K., Assel, M., Thong, A. E., Sjoberg, D. D., Mulhall, J. P., Sandhu, J., Vickers, A. J., Ehdaie, B. 2015; 68 (5): 899-905

    Abstract

    It is generally assumed that if a man does not regain urinary continence or erectile function within 12 mo of radical prostatectomy (RP), then the chance of subsequent recovery is low.To determine the probability of achieving good urinary function (UF) or erectile function (EF) up to 48 mo postoperatively in men who reported poor UF or EF at 12 mo after RP.We identified 3187 patients who underwent RP from 2007 through 2013 at a tertiary institution and had extended multidisciplinary follow-up with patient-reported UF and EF scores at ≥12 mo.Open or minimally invasive RP.Primary outcome was good UF as defined by a urinary score ≥17 (range: 0-21) or good EF as defined by a modified International Index of Erectile Function-6 score ≥22 (range: 1-30). The probability of functional recovery beyond 12 mo was determined by Kaplan-Meier analyses.Among patients incontinent at 12 mo, the probability of achieving good UF at 24, 36, and 48 mo was 30%, 49%, and 59%. In patients experiencing erectile dysfunction at 12 mo, the probability of recovering EF at 24, 36, and 48 mo was 22%, 32%, and 40%. On multivariable analyses, 12-mo functional score and age were associated with recovery, but only score was consistently significant.Men with incontinence or erectile dysfunction at 12 mo have higher than anticipated rates of subsequent functional improvement. Probability of recovery is strongly influenced by score at 12 mo. Further research should address the impact of ongoing multidisciplinary follow-up care on our observed rates of recovery.Many prostate cancer patients continue to recover urinary and erectile function after 12 mo. The level of functional recovery by 12 mo is associated with long-term recovery and should be discussed by the physician and patient when deciding on rehabilitative interventions.

    View details for DOI 10.1016/j.eururo.2015.07.074

    View details for Web of Science ID 000363475800037

    View details for PubMedID 26293181

    View details for PubMedCentralID PMC4605865

  • Development of a realistic in vivo bone metastasis model of human renal cell carcinoma CLINICAL & EXPERIMENTAL METASTASIS Valta, M. P., Zhao, H., Ingels, A., Thong, A. E., Nolley, R., Saar, M., Peehl, D. M. 2014; 31 (5): 573-584

    Abstract

    About one-third of patients with advanced renal cell carcinoma (RCC) have bone metastases. The incidence of RCC is increasing and bone metastatic RCC merits greater focus. Realistic preclinical bone metastasis models of RCC are lacking, hampering the development of effective therapies. We developed a realistic in vivo bone metastasis model of human RCC by implanting precision-cut tissue slices under the renal capsule of immunodeficient mice. The presence of disseminated cells in bone marrow of tissue slice graft (TSG)-bearing mice was screened by human-specific polymerase chain reaction and confirmed by immunohistology using human-specific antibody. Disseminated tumor cells in bone marrow of TSG-bearing mice derived from three of seven RCC patients were detected as early as 1 month after tissue implantation at a high frequency with close resemblance to parent tumors (e.g., CAIX expression and high vascularity). The metastatic patterns of TSGs correlated with disease progression in patients. In addition, TSGs retained capacity to metastasize to bone at high frequency after serial passaging and cryopreservation. Moreover, bone metastases in mice responded to Temsirolimus treatment. Intratibial injections of single cells generated from TSGs showed 100 % engraftment and produced X-ray-visible tumors as early as 3 weeks after cancer cell inoculation. Micro-computed tomography (μCT) and histological analysis revealed osteolytic characteristics of these lesions. Our results demonstrated that orthotopic RCC TSGs have potential to develop bone metastases that respond to standard therapy. This first reported primary RCC bone metastasis model provides a realistic setting to test therapeutics to prevent or treat bone metastases in RCC.

    View details for DOI 10.1007/s10585-014-9651-8

    View details for Web of Science ID 000337082400008

    View details for PubMedID 24715498

    View details for PubMedCentralID PMC4351963

  • Preclinical trial of a new dual mTOR inhibitor, MLN0128, using renal cell carcinoma tumorgrafts INTERNATIONAL JOURNAL OF CANCER Ingels, A., Zhao, H., Thong, A. E., Saar, M., Valta, M. P., Nolley, R., Santos, J., Peehl, D. M. 2014; 134 (10): 2322-2329

    Abstract

    mTOR is a rational target in renal cell carcinoma (RCC) because of its role in disease progression. However, the effects of temsirolimus, the only first-generation mTOR inhibitor approved by the FDA for first-line treatment of metastatic RCC, on tumor reduction and progression-free survival are minimal. Second-generation mTOR inhibitors have not been evaluated on RCC. We compared the effects of temsirolimus and MLN0128, a potent second-generation mTOR inhibitor, on RCC growth and metastasis using a realistic patient-derived tissue slice graft (TSG) model. TSGs were derived from three fresh primary RCC specimens by subrenal implantation of precision-cut tissue slices into immunodeficient mice that were randomized and treated with MLN0128, temsirolimus, or placebo. MLN0128 consistently suppressed primary RCC growth, monitored by magnetic resonance imaging (MRI), in three TSG cohorts for up to 2 months. Temsirolimus, in contrast, only transiently inhibited the growth of TSGs in one of two cohorts before resistance developed. In addition, MLN0128 reduced liver metastases, determined by human-specific quantitative polymerase chain reaction, in two TSG cohorts, whereas temsirolimus failed to have any significant impact. Moreover, MLN0128 decreased levels of key components of the two mTOR subpathways including TORC1 targets 4EBP1, p-S6K1, HIF1α and MTA1 and the TORC2 target c-Myc, consistent with dual inhibition. Our results demonstrated that MLN0128 is superior to temsirolimus in inhibiting primary RCC growth as well as metastases, lending strong support for further clinical development of dual mTOR inhibitors for RCC treatment.

    View details for DOI 10.1002/ijc.28579

    View details for Web of Science ID 000332309700007

    View details for PubMedID 24243565

    View details for PubMedCentralID PMC4365782

  • Relating prognosis in chromophobe renal cell carcinoma to the chromophobe tumor grading system. Korean journal of urology Weinzierl, E. P., Thong, A. E., McKenney, J. K., Jeon, S. H., Chung, B. I. 2014; 55 (4): 239-244

    Abstract

    The chromophobe subtype of renal cell carcinoma (chRCC) has generally been associated with a better prognosis than the clear cell type; however, debate continues as to absolute prognosis as well as the significance of certain prognostic variables. We investigated the significance of pathologic stage and a recently proposed chromophobe tumor grading (CTG) scheme in predicting chRCC outcomes.All available chRCCs were identified from our surgical pathology archives from 1987-2010. Original slides were reviewed to verify diagnoses and stage, and each case was graded following a novel chromophobe tumor grade system criteria. Disease status was obtained from a clinical outcome database, and cancer specific deaths and recurrences were recorded.Eighty-one cases of chRCC were identified, and 73 had adequate follow-up information available. There were only 3 instances of cancer related recurrence or mortality, which included 1 disease specific mortality and 2 disease recurrences. Pathologic stage and CTG 3 were found to be significantly associated with the recurrences or death from chRCC, but there was no association with CTG 1 and CTG 2.chRCC is associated with a very low rate of cancer specific events (4.1%) even at a tertiary referral center. In our study, pathologic stage and CTG 3, but not CTG 1 or 2, were significantly associated with the development of these events.

    View details for DOI 10.4111/kju.2014.55.4.239

    View details for PubMedID 24741411

  • Tissue slice grafts of human renal cell carcinoma: An authentic preclinical model with high engraftment rate and metastatic potential UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS Thong, A. E., Zhao, H., Ingels, A., Valta, M. P., Nolley, R., Santos, J., Young, S. R., Peehl, D. M. 2014; 32 (1)

    Abstract

    Discovery of curative therapies for renal cell carcinoma (RCC) is hampered by lack of authentic preclinical models. Tumorgrafts, generated by direct implantation of patient-derived tissues into mice, have demonstrated superior ability to predict therapeutic response. We evaluated "tissue slice grafts" (TSGs) as an improved tumorgraft model of RCC.Cores of fresh RCC were precision-cut at 300 µm and implanted under the renal capsule of RAG2(-/-)γC(-/-) mice. Engraftment rate, histology, biomarker expression, genetic fidelity, and metastatic potential were evaluated. Magnetic resonance imaging (MRI) was tested as a noninvasive method to measure tumor volume, and response to a targeted therapy was determined.All 13 cases of RCC engrafted and displayed characteristic histology and biomarkers. TSG volume quantified noninvasively by MRI highly correlated with graft weights, providing a unique tool for monitoring orthotopic growth. Moreover, in 2 cases, cancer cells from TSGs metastasized to clinically relevant sites, including bone. Microarray analysis and DNA sequencing demonstrated a high degree of correlation of global gene expression and von Hippel-Lindau (VHL) status between TSGs and parental tumors. Treatment of TSGs with sunitinib significantly decreased graft weight and mean vessel density compared with controls.The TSG model of RCC faithfully recapitulates tumor pathology, gene expression, genetic mutation, and drug response. The high engraftment rate and metastatic potential of this authentic model, in conjunction with the ability to generate large first-generation animal cohorts and to quantitate tumor volume at the orthotopic site by MRI, proffer significant advantages compared with other preclinical platforms.

    View details for DOI 10.1016/j.urolonc.2013.05.008

    View details for Web of Science ID 000347243300079

    View details for PubMedID 23911681

    View details for PubMedCentralID PMC4350678

  • Tissue slice grafts of human renal cell carcinoma: an authentic preclinical model with high engraftment rate and metastatic potential. Urologic oncology Thong, A. E., Zhao, H., Ingels, A., Valta, M. P., Nolley, R., Santos, J., Young, S. R., Peehl, D. M. 2014; 32 (1): 43 e23-30

    Abstract

    Discovery of curative therapies for renal cell carcinoma (RCC) is hampered by lack of authentic preclinical models. Tumorgrafts, generated by direct implantation of patient-derived tissues into mice, have demonstrated superior ability to predict therapeutic response. We evaluated "tissue slice grafts" (TSGs) as an improved tumorgraft model of RCC.Cores of fresh RCC were precision-cut at 300 µm and implanted under the renal capsule of RAG2(-/-)γC(-/-) mice. Engraftment rate, histology, biomarker expression, genetic fidelity, and metastatic potential were evaluated. Magnetic resonance imaging (MRI) was tested as a noninvasive method to measure tumor volume, and response to a targeted therapy was determined.All 13 cases of RCC engrafted and displayed characteristic histology and biomarkers. TSG volume quantified noninvasively by MRI highly correlated with graft weights, providing a unique tool for monitoring orthotopic growth. Moreover, in 2 cases, cancer cells from TSGs metastasized to clinically relevant sites, including bone. Microarray analysis and DNA sequencing demonstrated a high degree of correlation of global gene expression and von Hippel-Lindau (VHL) status between TSGs and parental tumors. Treatment of TSGs with sunitinib significantly decreased graft weight and mean vessel density compared with controls.The TSG model of RCC faithfully recapitulates tumor pathology, gene expression, genetic mutation, and drug response. The high engraftment rate and metastatic potential of this authentic model, in conjunction with the ability to generate large first-generation animal cohorts and to quantitate tumor volume at the orthotopic site by MRI, proffer significant advantages compared with other preclinical platforms.

    View details for DOI 10.1016/j.urolonc.2013.05.008

    View details for PubMedID 23911681

  • Estimating the risk of chronic kidney disease after nephrectomy CANADIAN JOURNAL OF UROLOGY Ngo, T. C., Hurley, M. P., Thong, A. E., Jeon, S. H., Leppert, J. T., Chung, B. I. 2013; 20 (6): 7035-7041

    Abstract

    To identify factors associated with the development of chronic kidney disease (CKD) after nephrectomy and to create a clinical model to predict CKD after nephrectomy for kidney cancer for clinical use.We identified 144 patients who had normal renal function (eGFR > 60) prior to undergoing nephrectomy for kidney cancer. Selected cases occurred between 2007 and 2010 and had at least 30 days follow up. Sixty-six percent (n = 95) underwent radical nephrectomy and 62.5% (n = 90) developed CKD (stage 3 or higher) postoperatively. We used univariable analysis to screen for predictors of CKD and multivariable logistic regression to identify independent predictors of CKD and their corresponding odds ratios. Interaction terms were introduced to test for effect modification. To protect against over-fitting, we used 10-fold cross-validation technique to evaluate model performance in multiple training and testing datasets. Validation against an independent external cohort was also performed.Of the variables associated with CKD in univariable analysis, the only independent predictors in multivariable logistic regression were patient age (OR = 1.27 per 5 years, 95% CI: 1.07-1.51), preoperative glomerular filtration rate (GFR), (OR = 0.70 per 10 mL/min, 95% CI: 0.56-0.89), and receipt of radical nephrectomy (OR = 4.78, 95% CI: 2.08-10.99). There were no significant interaction terms. The resulting model had an area under the curve (AUC) of 0.798. A 10-fold cross-validation slightly attenuated the AUC to 0.774 and external validation yielded an AUC of 0.930, confirming excellent model discrimination.Patient age, preoperative GFR, and receipt of a radical nephrectomy independently predicted the development of CKD in patients undergoing nephrectomy for kidney cancer in a validated predictive model.

    View details for Web of Science ID 000328717300007

    View details for PubMedID 24331345

  • Nano-scale proteomic profiling to define diagnostic signatures and biomarkers of therapeutic activity in patients with RCC Leppert, J. T., Fan, A. C., Metzner, T., Liliental, J. E., Xu, L., Thong, A. E., Yost, C., Yaghi, A., Brooks, J. D., Harshman, L. C., Sabatti, C., Srinivas, S., Felsher, D. W. WILEY-BLACKWELL. 2013: 14
  • Stage I Testicular Seminoma: A SEER Analysis of Contemporary Adjuvant Radiotherapy Trends. journal of urology Thong, A. E., Lichtensztajn, D. Y., Almario, L., Ingels, A., Gomez, S. L., Gonzalgo, M. L. 2013; 190 (4): 1240-1244

    Abstract

    PURPOSE: Patients with clinical stage I testicular seminoma have historically been treated with adjuvant radiotherapy (RT) in the United States. However, nearly 80% of patients on surveillance will not relapse and even with relapse, salvage rates approach 100%. It remains unclear how practice patterns have changed with recently accumulating evidence and changes in guidelines. We evaluated, in a population-based setting, contemporary trends and factors that may affect utilization of adjuvant RT. MATERIALS AND METHODS: A total of 8,151 men from 2000 to 2009 diagnosed with stage I testicular seminoma were identified in the national Surveillance, Epidemiology, and End Results (SEER) registry. A multivariate regression model was constructed to analyze the association of year, age, race, socioeconomic status, SEER region, pathologic stage, and tumor size with administration of adjuvant RT. RESULTS: Utilization of adjuvant RT significantly decreased from 2000 to 2009. In 2000, 74.7% of patients received radiation, compared with only 37.7% of patients in 2009 (p<0.0001). Later year of diagnosis was significantly associated with decreased odds of receiving adjuvant RT (p<0.0001, 2000-2005 vs. 2006-2009, Odds ratio (OR) 0.40, 95% CI 0.36-0.44). Men older than 35 years (p<0.0002, OR 1.20, 95% CI 1.09-1.32) and men in the highest socioeconomic index quartile (p<0.0001, OR 1.34, 95% CI 1.16-1.54) were more likely to receive adjuvant RT. CONCLUSIONS: Utilization of adjuvant RT for clinical stage I testicular seminoma has decreased significantly in the last decade. Older age and higher socioeconomic status were associated with higher rates of adjuvant RT.

    View details for DOI 10.1016/j.juro.2013.03.114

    View details for PubMedID 23567749

  • Patient-derived tissue slice grafts accurately depict response of high-risk primary prostate cancer to androgen deprivation therapy JOURNAL OF TRANSLATIONAL MEDICINE Zhao, H., Thong, A., Nolley, R., Reese, S. W., Santos, J., Ingels, A., Peehl, D. M. 2013; 11

    Abstract

    Effective eradication of high-risk primary prostate cancer (HRPCa) could significantly decrease mortality from prostate cancer. However, the discovery of curative therapies for HRPCa is hampered by the lack of authentic preclinical models.We improved upon tumorgraft models that have been shown to predict drug response in other cancer types by implanting thin, precision-cut slices of HRPCa under the renal capsule of immunodeficient mice. Tissue slice grafts (TSGs) from 6 cases of HRPCa were established in mice. Following androgen deprivation by castration, TSGs were recovered and the presence and phenotype of cancer cells were evaluated.High-grade cancer in TSGs generated from HRPCa displayed characteristic Gleason patterns and biomarker expression. Response to androgen deprivation therapy (ADT) was as in humans, with some cases exhibiting complete pathologic regression and others showing resistance to castration. As in humans, ADT decreased cell proliferation and prostate-specific antigen expression in TSGs. Adverse pathological features of parent HRPCa were associated with lack of regression of cancer in corresponding TSGs after ADT. Castration-resistant cancer cells remaining in TSGs showed upregulated expression of androgen receptor target genes, as occurs in castration-resistant prostate cancer (CRPC) in humans. Finally, a rare subset of castration-resistant cancer cells in TSGs underwent epithelial-mesenchymal transition, a process also observed in CRPC in humans.Our study demonstrates the feasibility of generating TSGs from multiple patients and of generating a relatively large number of TSGs from the same HRPCa specimen with similar cell composition and histology among control and experimental samples in an in vivo setting. The authentic response of TSGs to ADT, which has been extensively characterized in humans, suggests that TSGs can serve as a surrogate model for clinical trials to achieve rapid and less expensive screening of therapeutics for HRPCa and primary CRPC.

    View details for DOI 10.1186/1479-5876-11-199

    View details for Web of Science ID 000323850900001

    View details for PubMedID 23985008

    View details for PubMedCentralID PMC3766103

  • Patient-derived tissue slice grafts of high-risk primary prostate cancer: An authentic preclinical model for synthetic lethality-based therapy Zhao, H., Thong, A., Nolley, R., Reese, S., Santos, J., Ingels, A., Peehl, D. AMER ASSOC CANCER RESEARCH. 2013
  • NANO-SCALE PROTEOMIC PROFILING TO DEFINE DIAGNOSTIC SIGNATURES AND BIOMARKERS OF THERAPEUTIC ACTIVITY IN RCC Leppert, J., Fan, A., Liliental, J., Xu, L., Thong, A., Yost, C., Yaghi, A., Metzner, T., Brooks, J., Harshman, L., Sabatti, C., Srinivas, S., Felsher, D. ELSEVIER SCIENCE INC. 2013: E246–E247
  • PRE-CLINICAL TRIAL OF A NEW DUAL MTOR INHIBITOR: INK128 FOR RENAL CELL CARCINOMA Ingels, A., Thong, A., Saar, M., Valta, M., Nolley, R., Santos, J., Zhao, H., Peehl, D. ELSEVIER SCIENCE INC. 2013: E65
  • Nanoscale proteomic profiling to define diagnostic signatures and biomarkers of therapeutic activity in patients with RCC Fan, A. C., Leppert, J., Liliental, J. E., Xu, L., Thong, A. E., Yost, C., Yaghi, A., Brooks, J. D., Harshman, L., Sabatti, C., Srinivas, S., Felsher, D. W. AMER SOC CLINICAL ONCOLOGY. 2013
  • Mouse model of primary human renal cell carcinoma metastasis to bone Valta, M., Zhao, H., Ingels, A., Thong, A., Nolley, R., Saar, M., Peehl, D. AMER ASSOC CANCER RESEARCH. 2013
  • Comparison of Three Different Tools for Prediction of Seminal Vesicle Invasion at Radical Prostatectomy EUROPEAN UROLOGY Lughezzani, G., Zorn, K. C., Budaeus, L., Sun, M., Lee, D. I., Shalhav, A. L., Zagaya, G. P., Shikanov, S. A., Gofrit, O. N., Thong, A. E., Albala, D. M., Sun, L., Cronin, A., Vickers, A. J., Karakiewicz, P. I. 2012; 62 (4): 590-596

    Abstract

    Statistical prediction tools are increasingly common, but there is considerable disagreement about how they should be evaluated. Three tools--Partin tables, the European Society for Urological Oncology (ESUO) criteria, and the Gallina nomogram--have been proposed for the prediction of seminal vesicle invasion (SVI) in patients with clinically localized prostate cancer who are candidates for a radical prostatectomy.Using different statistical methods, we aimed to determine which of these tools should be used to predict SVI.The independent validation cohort consisted of 2584 patients treated surgically for clinically localized prostate cancer at four North American tertiary care centers between 2002 and 2007.Robot-assisted laparoscopic radical prostatectomy.Primary outcome was the presence of SVI. Traditional (area under the receiver operating characteristic [ROC] curve, calibration plots, the Brier score, sensitivity and specificity, positive and negative predictive value) and novel (decision curve analysis and predictiveness curves) statistical methods quantified the predictive abilities of the three models.Traditional statistical methods (ie, ROC plots and Brier scores) could not clearly determine which one of the three SVI prediction tools should be preferred. For example, ROC plots and Brier scores seemed biased against the binary decision tool (ESUO criteria) and gave discordant results for the continuous predictions of the Partin tables and the Gallina nomogram. The results of the calibration plots were discordant with those of the ROC plots. Conversely, the decision curve indicated that the Partin tables represent the best strategy for stratifying the risk of SVI, resulting in the highest net benefit within the whole range of threshold probabilities.When predicting SVI, surgeons should prefer the Partin tables over the ESUO criteria and the Gallina nomogram because this tool provided the highest net benefit. In contrast to traditional statistical methods, decision curve analysis gave an unambiguous result applicable to both continuous and binary models, providing an insight into clinical utility.

    View details for DOI 10.1016/j.eururo.2012.04.022

    View details for Web of Science ID 000308563100010

    View details for PubMedID 22561078

    View details for PubMedCentralID PMC3674492

  • Learning From Our Patients: Complications and the Future of Radical Cystectomy for Bladder Cancer JOURNAL OF UROLOGY Thong, A. E., Gonzalgo, M. L. 2012; 187 (6): 2018-2018

    View details for DOI 10.1016/j.juro.2012.03.032

    View details for Web of Science ID 000303821300017

    View details for PubMedID 22579165

  • ESTIMATING THE RISK OF CHRONIC KIDNEY DISEASE AFTER NEPHRECTOMY Tin Ngo, Hurley, M., Thong, A., Jeon, S., Leppert, J., Chung, B. ELSEVIER SCIENCE INC. 2012: E584
  • CLINICOPATHOLOGIC FEATURES AND OUTCOMES OF A CHROMOPHOBE RENAL CELL CARCINOMA SERIES FROM A SINGLE INSTITUTION Thong, A., Tin Ngo, Weinzierl, E., Leppert, J., McKenney, J., Chung, B. ELSEVIER SCIENCE INC. 2012: E240
  • Evolution of Open Radical Retropubic Prostatectomy-How Have Open Surgeons Responded to the Challenge of Minimally Invasive Surgery? JOURNAL OF ENDOUROLOGY Acharya, S. S., Zorn, K. C., Shikanov, S., Thong, A., Zagaja, G. P., Shalhav, A. L., Steinberg, G. D. 2009; 23 (11): 1893-1897

    Abstract

    With the advent of minimally invasive surgery (MIS) for treating urologic malignancies, emphasis has been placed on reducing patient morbidity and resuming normal activity. We sought to clarify whether open surgeons (OS) have modified their techniques, surgical equipment, and perioperative management in response to this trend.A survey sent to all members of the Society of Urologic Oncology assessed changes that OS performing radical retropubic prostatectomy have made in analgesia, operative technique, perioperative management, and follow-up patterns. We also assessed OS sense of competition from MIS. Surgeon perception of the influence MIS had on these changes was scored from 0 to 4 (0 = not at all, 1 = slightly, 2 = moderately, 3 = greatly, 4 =completely). Overall and major influence by MIS included scores 1-4 and 3-4, respectively.Reduced radical retropubic prostatectomy (RRP) case volume because of MIS competition was reported by 20 OS (24%), with 27 OS (32%) starting to perform MIS, and 20 (24%) doing mostly/exclusively MIS. MIS has influenced OS to reduce incision length (overall influence 56%/major influence 33%), operative time (40%/12%), blood loss (31%/17%), and transfusion rate (33%/14%). MIS has influenced OS to use new instruments (48%/44%) or loupes (20%/9%), modify dissection (45%/31%) or anastomotic technique (14%/12%), and increase the use of hemostatic agents (48%/19%). MIS has reduced convalescence in OS patients by reducing length of stay (52%/28%), time to a regular diet (40%/18%), duration of drain (21%/16%) and Foley (32%/15%), time to return to work (49%/25%), and exercise (44%/21%). MIS has changed follow-up of OS patients by increasing the use of clinical pathways (14%/9%) and validated questionnaires (22%/13%).To date, the influence of MIS on the OS has not been comprehensively assessed. This survey finds that OS report that MIS serves as major competition to the open technique and that it has influenced them to modify their surgical technique, reduce convalescence, and alter follow-up recommendations.

    View details for DOI 10.1089/end.2008.0509

    View details for Web of Science ID 000271505300019

    View details for PubMedID 19630483

  • Continued improvement of perioperative, pathological and continence outcomes during 700 robot-assisted radical prostatectomies CANADIAN JOURNAL OF UROLOGY Zorn, K. C., Wille, M. A., Thong, A. E., Katz, M. H., Shikanov, S. A., Razmaria, A., Gofrit, O. N., Zagaja, G. P., Shalhav, A. L. 2009; 16 (4): 4742-4749

    Abstract

    Several robot-assisted radical prostatectomy (RARP) series have reviewed the impact of the initial learning curve on perioperative outcomes. However, little is known about the impact of experience on urinary and sexual outcomes. Herein, we review the perioperative, pathological and functional outcomes of our initial 700 consecutive procedures with at least 1 year follow up.From 2003-2006, 700 consecutive men underwent RARP at a single, academic institution. Perioperative data and pathologic outcomes were prospectively collected. Validated, UCLA-PCI-SF36v2 quality-of-life questionnaires were also obtained at 1, 3, 6 and 12 months following surgery. Outcomes between groups (cases 1-300, 301-500, and 501-700) were compared.Mean operative time (OT) and blood loss significantly decreased during the experience (286, 198, 190 min; p or=7 in 24%, 40%, 44%; p

    View details for Web of Science ID 000268985000008

    View details for PubMedID 19671227

  • MULTI-INSTITUTIONAL EXTERNAL VALIDATION OF SEMINAL VESICLE INVASION NOMOGRAMS: HEAD-TO-HEAD COMPARISON OF GALLINA NOMOGRAM VERSUS 2007 PARTIN TABLES INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Zorn, K. C., Capitanio, U., Jeldres, C., Arjane, P., Perrotte, P., Shariat, S. F., Lee, D. I., Shalhav, A. L., Zagaja, G. P., Shikanov, S. A., Gofrit, O. N., Thong, A. E., Albala, D. M., Sun, L., Karakiewicz, P. I. 2009; 73 (5): 1461-1467

    Abstract

    The Partin tables represent one of the most widely used prostate cancer staging tools for seminal vesicle invasion (SVI) prediction. Recently, Gallina et al. reported a novel staging tool for the prediction of SVI that further incorporated the use of the percentage of positive biopsy cores. We performed an external validation of the Gallina et al. nomogram and the 2007 Partin tables in a large, multi-institutional North American cohort of men treated with robotic-assisted radical prostatectomy.Clinical and pathologic data were prospectively gathered from 2,606 patients treated with robotic-assisted radical prostatectomy at one of four North American robotic referral centers between 2002 and 2007. Discrimination was quantified with the area under the receiver operating characteristics curve. The calibration compared the predicted and observed SVI rates throughout the entire range of predictions.At robotic-assisted radical prostatectomy, SVI was recorded in 4.2% of patients. The discriminant properties of the Gallina et al. nomogram resulted in 81% accuracy compared with 78% for the 2007 Partin tables. The Gallina et al. nomogram overestimated the true rate of SVI. Conversely, the Partin tables underestimated the true rate of SVI.The Gallina et al. nomogram offers greater accuracy (81%) than the 2007 Partin tables (78%). However, both tools are associated with calibration limitations that need to be acknowledged and considered before their implementation into clinical practice.

    View details for DOI 10.1016/j.ijrobp.2008.06.1913

    View details for Web of Science ID 000264728000024

    View details for PubMedID 18938046

  • Robotic Radical Prostatectomy in Overweight and Obese Patients: Oncological and Validated-Functional Outcomes UROLOGY Wiltz, A. L., Shikanov, S., Eggener, S. E., Katz, M. H., Thong, A. E., Steinberg, G. D., Shalhav, A. L., Zagaja, G. P., Zorn, K. C. 2009; 73 (2): 316-322

    Abstract

    To determine the impact of body mass index (BMI) on perioperative functional and oncological outcomes in patients undergoing robotic laparoscopic radical prostatectomy (RLRP) when stratified by BMI.Data were collected prospectively for 945 consecutive patients undergoing RLRP. Patients were evaluated with the UCLA-PCI-SF36v2 validated-quality-of-life questionnaire preoperatively and postoperatively to 24 months. Patients were stratified by BMI as normal weight (BMI < 25 kg/m(2)), overweight (BMI = 25 to < 30 kg/m(2)) and obese (BMI > or = 30 kg/m(2)) for outcomes analysis.Preoperatively, obese men had a significantly greater percentage of medical comorbidities (P < .01) as well as a baseline erectile dysfunction (lower mean baseline Sexual Health Inventory for Men score [P = .01] and UCLA-PCI-SF36v2 sexual function domain scores [P = .01]). Mean operative time was significantly longer in obese patients when compared with normal and overweight men (234 minutes vs 217 minutes vs 214 minutes; P = .0003). Although overall complication rates were comparable between groups, a greater incidence of case abortion caused by pneumoperitoneal pressure with excessive airway pressures was noted in obese men. Urinary continence and potency outcomes were significantly lower for obese men at both 12 and 24 months (all P < .05).In this series, obese men experienced a longer operative time, particularly during the initial robotic experience. As such, surgeons early in their RLRP learning curve should proceed cautiously with surgery in these technically more difficult patients or reserve such cases until the learning curve has been surmounted. These details, including inferior urinary and sexual outcomes, should be discussed with obese patients during preoperative counseling.

    View details for DOI 10.1016/j.urology.2008.08.493

    View details for Web of Science ID 000264038100027

    View details for PubMedID 18952266

  • A Single Microfocus (5% or Less) of Gleason 6 Prostate Cancer at Biopsy-Can We Predict Adverse Pathological Outcomes? JOURNAL OF UROLOGY Thong, A. E., Shikanov, S., Katz, M. H., Gofrit, O. N., Eggener, S., Zagaja, G. P., Shalhav, A. L., Zorn, K. C. 2008; 180 (6): 2436-2440

    Abstract

    Patients with Gleason score 6 microfocal prostate cancer, defined as 5% or less in 1 biopsy core, are often considered to have favorable disease. Few studies have addressed clinical parameters that predict pathological upgrading or up staging at radical prostatectomy.From a prospective database of 1,271 consecutive robot assisted laparoscopic prostatectomies performed from 2003 to 2008 patients with Gleason score 6 microfocal prostate cancer were identified. Adverse pathological outcome was defined as any upgrading and/or up staging on prostatectomy pathological findings. Multivariate logistic regression was used to evaluate the ability of patient age, clinical stage, the total number of biopsy cores, preoperative prostate specific antigen, prostate volume and pathological prostate specific antigen density to predict adverse pathological outcomes.A total of 192 patients with a median age of 59 years (range 42 to 73) were identified with Gleason score 6 prostate cancer involving 5% or less of 1 biopsy core, including 177 (92%) with clinical T1c disease. Mean +/- SD preoperative prostate specific antigen was 6.0 +/- 3.9 ng/ml (range 0.8 to 35). Overall 42 patients (22%) had adverse pathological outcomes, including upgrading in 35 (18%) and up staging in 16 (8%). Multivariate logistic regression revealed that age more than 65 years and pathological prostate specific antigen density greater than 0.20 ng/ml/gm were predictive of an increased risk of adverse pathological results (p = 0.0081 and 0.0169, respectively).While a microfocus of Gleason score 6 prostate cancer on biopsy is commonly considered low risk disease, there was a greater than 1/5 risk of pathological upgrading and/or up staging. Patients with Gleason score 6 microfocal prostate cancer should be counseled that they may harbor more aggressive disease, especially when pretreatment clinical risk factors are present, such as advanced age or high clinical prostate specific antigen density.

    View details for DOI 10.1016/j.juro.2008.08.027

    View details for Web of Science ID 000260982200050

    View details for PubMedID 18930486

  • Robotic laparoscopic radical prostatectomy for biopsy gleason 8 to 10: Prediction of favorable pathologic outcome with preoperative parameters JOURNAL OF ENDOUROLOGY Shikanov, S. A., Thong, A., Gofrit, O. N., Zagaja, G. P., Steinberg, G. D., Shalhav, A. L., Zorn, K. C. 2008; 22 (7): 1477-1481

    Abstract

    We sought to evaluate the pathologic results and postoperative outcomes for men undergoing robot-assisted laparoscopic radical prostatectomy (RLRP) for biopsy Gleason score (GS) 8 to 10 disease. Stratification of these patients according to preoperative variables was also performed in an attempt to predict organ-confined cancer.A prospective RLRP database identified all patients with preoperative biopsy GS 8 to 10. Variables, including prostate-specific antigen (PSA), percent positive biopsy cores (%PBC), maximal percentage of cancer in biopsy core (%MCB), clinical stage, pathologic stage, pathologic GS, surgical margins status, lymph node status, time to biochemical recurrence, and recurrence rate, were evaluated. Preoperative variables were treated as continuous and categorical using PSA, %PBC and %MCB cutoffs of 10 ng/mL, 50%, and 30%, respectively.Between February 2003 and September 2007, a total of 1225 RLRPs were performed at the University of Chicago Medical Center. Seventy-two (5.9%) patients had preoperative biopsy GS 8 to 10. Two patients received neoadjuvant hormonal therapy and were excluded. Among 70 patients evaluated, 33 (47%) had organconfined (pT(2)N0) disease. Forty (60.6%) patients had pathologic downgrading to GS

    View details for DOI 10.1089/end.2008.0091

    View details for Web of Science ID 000258385000014

    View details for PubMedID 18613786

  • The cemented all-polyethylene acetabular cup: Factors affecting survival with emphasis on the integrated polyethylene spacer - An analysis of the effect of cement spacers, cement mantle thickness, and acetabular angle on the survival of total hip arthroplasty JOURNAL OF ARTHROPLASTY Faris, P. M., Ritter, M. A., Keating, E. M., Thong, A. E., Davis, K. E., Meding, J. B. 2006; 21 (2): 191-198

    Abstract

    Four hundred seven primary total hip arthroplasties were performed using a cemented, direct compression molded all-polyethylene acetabular component. Based on a double-blinded randomization schedule, one group received acetabular cups with cement spacers made from polyethylene integrated into the cup, whereas the other group received the same acetabular cups with the polyethylene spacers removed. Patients were followed up for an average of 6.5 years. During this follow-up period, there were 3 revisions for acetabular cup loosening and 40 acetabular cups that had a global radiolucent line at least 1 mm wide. Acetabular cups with polyethylene spacers were found to have a significantly higher initial rate of failure (P < .0380) when compared with cups without cement spacers. Yet, polyethylene spacers resulted in a significantly thicker and more uniform cement mantle in zones 1, 2, and 3 (P < .0001). Cups initially placed at an angle of 45.0 degrees to 50.5 degrees had the highest survival rate compared with all possible angle ranges (P < .0158).

    View details for Web of Science ID 000236480100008

    View details for PubMedID 16520206

  • The effect of femoral notching during total knee arthroplasty on the prevalence of postoperative femoral fractures and on clinical outcome. journal of bone and joint surgery. American volume Ritter, M. A., Thong, A. E., Keating, E. M., Faris, P. M., Meding, J. B., Berend, M. E., Pierson, J. L., Davis, K. E. 2005; 87 (11): 2411-2414

    Abstract

    The treatment of a supracondylar femoral fracture following total knee arthroplasty is complicated by the presence of the prosthetic components. Anterior femoral notching during arthroplasty has been implicated as a contributing risk factor for femoral fracture. We retrospectively reviewed the effect of anterior femoral notching on the subsequent occurrence of a periprosthetic supracondylar fracture of the distal aspect of the femur and the outcomes of primary total knee arthroplasty in such patients.The prevalence and depth of femoral notching were determined on a review of the lateral radiographs by observers blinded to the clinical results of 1089 consecutive total knee replacements performed in 1997 and 1998. Linear and logistic regression modeling was used to analyze the relationship between femoral notching and the prevalence of supracondylar femoral fracture, postoperative range of motion, the Knee Society score, and the Knee Society functional and pain scores.Femoral notching was performed in 325 (29.8%) of the 1089 knees in our series. During an average follow-up period of 5.1 years, only two supracondylar femoral fractures occurred, both in femora treated without notching. Femoral notching was not associated with an increased rate of fracture (p = 1.000) or with significant differences in the measures of outcome (range of motion [p = 0.117], knee score [p = 0.967], functional score [p = 0.861], need for a lateral release [p = 0.234], or postoperative pain [p = 0.948]).This study demonstrated no difference in knees managed with or without notching of the anterior distal aspect of the femur with respect to the occurrence of a supracondylar fracture, range of motion, Knee Society score, Knee Society function, or pain.

    View details for PubMedID 16264115

  • Simultaneous bilateral versus unilateral total hip arthroplasty - An outcomes analysis JOURNAL OF ARTHROPLASTY Berend, M. E., Ritter, M. A., Harty, L. D., Davis, K. E., Keating, E. M., Meding, J. B., Thong, A. E. 2005; 20 (4): 421-426

    Abstract

    This study compared the morbidity, mortality, and outcomes of 900 simultaneous bilateral total hip arthroplasties in 450 patients and 450 unilateral total hip arthroplasties. Pulmonary complications were significantly higher in the simultaneous bilateral group (1.6% vs 0.7%; P < .0312). Fourteen (3.1%) patients in the simultaneous bilateral group and 18 (4%) patients in the unilateral group died within the first postoperative year. Patients with mortality in the first postoperative year were significantly older (69.8 vs 62.3 years; P < .0012). Long-term patient survival, the prosthetic survival, and functional outcomes were not significantly different between groups. Simultaneous bilateral total hip arthroplasty has advantages where both hips are symptomatic and has less risk in younger patients with understanding of the increased risk of pulmonary complications.

    View details for DOI 10.1016/j.arth.2004.09.062

    View details for Web of Science ID 000230039300003

    View details for PubMedID 16124956

  • The role of cemented sockets in 2004 - Is there one? JOURNAL OF ARTHROPLASTY Ritter, M. A., Thong, A. E. 2004; 19 (4): 92-94

    Abstract

    Cement fixation of the acetabular cup in total hip arthroplasty (THA) has evolved through multiple generations of cement technology. Whereas cement technology has produced improvements in cemented femoral fixation, the cemented socket still produces inconsistent results. Even with our current knowledge that cemented cups require exposure of cancellous bone, a clean and dry socket, and adequate bony coverage of the cup, surgeons such as myself are unable to control radiolucency at the bone-cement interface. The technical difficulty of cementing the acetabular cup has led to the increasing prevalence of cementless acetabular cups. Although cementless fixation has resulted in increased incidence of osteolysis, the surgical procedure is less technically demanding, and the long-term mechanical fixation results have been more consistent. Given the experiential learning curve that most orthopedic surgeons face with cemented fixation of the acetabular cup component, the role of the cemented socket in THA today is limited.

    View details for DOI 10.1016/j.arth.2004.02.006

    View details for Web of Science ID 000222353400021

    View details for PubMedID 15190559

  • Long-term deterioration of joint evaluation scores. journal of bone and joint surgery. British volume Ritter, M. A., Thong, A. E., Davis, K. E., Berend, M. E., Meding, J. B., Faris, P. M. 2004; 86 (3): 438-442

    Abstract

    We investigated the long-term changes in the Harris Hip and Knee Society scores (HSS and KSS) to determine whether they result from overall functional decline rather than actual changes in the condition of the prosthesis. The HHS for 106 total hip arthroplasties with a minimum follow-up of ten years, no medical complications after operation and no evidence of radiological loosening, and the KSS for 264 total knee arthroplasties with a minimum follow-up of 12 years and no medical complications after operation or signs of radiographical loosening were evaluated. There were statistically significant drops in the functional scoring components of the joint evaluation systems despite no loosening of the prostheses or other significant medical complications. The HHS declined at an average of 0.67 points per year from between three and ten years after operation (p < 0.0001). Contributing to this were deterioration in gait and limp (p < 0.0004), the use of support aids (p < 0.0001), the distance walked (p < 0.0001) and the ability to climb stairs (p < 0.0455). The functional component of the KSS declined significantly at an average 0.88 points per year betwen the third and 12th years (p < 0.0001). There were significant declines in every component of the functional score including the distance walked (p < 0.0001), the ability to climb stairs (p < 0.0001) and the use of support aids (p < 0.0001). The knee score component of the KSS did not decline significantly (p < 0.9750). The combination of functional and pain scores within the HHS system leads to an inaccurate decline in the entire score. The decline of HHS and Knee Society functional scores in total joint arthroplasties, in the absence of implant-related problems, suggests that deterioration in the functional capacity of ageing patients is an important factor in longitudinal studies using these scoring systems.

    View details for PubMedID 15125135

  • Intra-operative findings in varus osteoarthritis of the knee. An analysis of pre-operative alignment in potential candidates for unicompartmental arthroplasty. journal of bone and joint surgery. British volume Ritter, M. A., Faris, P. M., Thong, A. E., Davis, K. E., Meding, J. B., Berend, M. E. 2004; 86 (1): 43-47

    Abstract

    Interest in unicompartmental knee arthroplasty (UKA) for the treatment of medial compartment osteoarthritis has increased in recent years with apparent improvement in the long-term results. This is a result of improved surgical technique, patient selection, and implant design. In an effort further to improve patient selection we analysed the relationship between the pre-operative alignment of the knee and the anatomical findings at the time of surgery. We compared these findings with the indications for UKA. From 4021 total knee arthroplasties we compared intra-operative observations with the pre-operative clinical data in order to identify knees with isolated, medial, compartment changes, which would have been ideal candidates for UKA. We found that only 247 of the knees (6.1%) met anatomical qualifications for isolated, medial, unicompartmental osteoarthritis, and of these, only 168 (4.3%) met clinical standards ideal for UKA. Preoperative alignment showed a significant relationship with patterns of disease. Logistic regression revealed a relationship between pre-operative alignment and intraoperative findings resembling a Gaussian distribution. Patients with a pre-operative varus alignment of 7 degrees were slightly more likely to be selected for UKA. But the further the anatomical alignment in either direction varies from 7 degrees of varus, the more unlikely it is for the knee to exhibit a disease pattern of isolated, medial, unicompartmental osteoarthritis.

    View details for PubMedID 14765864

  • Total joint arthroplasty in the extremely elderly - Hip and knee arthroplasty after entering the 89th year of life JOURNAL OF ARTHROPLASTY Berend, M. E., Thong, A. E., Faris, G. W., Newbern, G., Pierson, J. L., Ritter, M. A. 2003; 18 (7): 817-821

    Abstract

    The goal of this study was to evaluate the complications and efficacy of total joint arthroplasty in the extremely elderly and compare the survival with the normal age-matched population. One hundred one joint arthroplasties (45 total knee arthroplasties [TKAs], 56 total hip arthroplasties [THAs]) were performed in 83 patients 89 years old and older. Over an average follow-up period of 2.5 years, 26 (31%) of the patients died. Three patients (3.6%) died within the first 2 months' postoperatively. The perioperative medical complication rate (excluding deaths) was 14%. Significant improvements were noted in pain scores, Harris Hip Scores, and Knee Society Scores. The survival of patients in their nineties who undergo total joint arthroplasty is at least equal to the survival of an age-matched population for 2.5 years following surgery. With careful patient selection and patient care to minimize medical complications, total joint arthroplasty can be an excellent option for patients who are age 89 and older.

    View details for DOI 10.1054/S0883-5403(03)00338-3

    View details for Web of Science ID 000185968000001

    View details for PubMedID 14566733