Two-stage classifiers that minimize PCA3 and the PSA proteolytic activity testing in the prediction of prostate cancer recurrence after radical prostatectomy.

INTRODUCTION: Early biochemical recurrence after prostate cancer surgery is associated with higher risk of aggressive disease and cancer specific death. Many new tests are being developed that will predict the presence of indicators of aggressive disease like early biochemical recurrence. Since recurrence occurs in less than 10% of patients treated for prostate cancer, validation of such tests will require expensive testing on large patient groups. Moreover, clinical application of the validated test requires that each new patient be tested. In this report we introduce a two-stage classifier system that minimizes the number of patients that must be tested in both the validation and clinical application of any new test for recurrence. MATERIALS AND METHODS: Expressed prostatic secretion specimens were prospectively collected from 450 patients prior to robot-assisted radical prostatectomy for prostate cancer. Patients were followed for 2.5 years for evidence of biochemical recurrence. Standard clinical parameters, the levels proteolytic activity of prostate specific antigen (PSA) and the levels of PCA3 RNA, PSA RNA and TMPRSS2:ERG fusion RNA were determined in each prospective patient specimen for subsequent correlation with biochemical recurrence. RESULTS: While levels of PCA3 and PSA proteolytic activity (PPA) in prostatic secretions provided an effective pre-surgical predictor of early biochemical recurrence in prostate cancer, application of the two-stage classifier shows that only 60% of the patients need these tests. CONCLUSION: Two-stage classifiers can provide a parsimonious approach to both the validation and clinical application of biomarker-based tests. Adoption of the two-stage neutral zone classifier can reduce unnecessary testing in prostate cancer treatment.

Presurgical Biomarker Performance in the Detection of Gleason Upgrading in Prostate Cancer.

BACKGROUND: Gleason Score (GS) upgrading is generally considered a trigger for exit to definitive treatment during active surveillance (AS). Predicting the potential for GS upgrading would be of value in assessing AS eligibility. METHODS: We assessed the performance of biomarkers in presurgical specimens of expressed prostatic secretion (EPS) in this setting. RESULTS: Although EPS volume, total recovered RNA, and RNA expression biomarkers (TMPRSS2: ERG, PCA3, PSA) have been successful in both biopsy outcome prediction, and in the prediction of upstaging in active surveillance eligible patients, they were unable to predict upgrading in patients eligible for active surveillance under National Comprehensive Cancer Network guidelines. CONCLUSIONS: These biomarkers do not improve the prediction of upgrading over indications from standard clinical parameters. IMPACT: Additional biomarkers will be needed in this area. Cancer Epidemiol Biomarkers Prev; 25(12); 1643-5. ©2016 AACR.

Critical Analysis of Hospital Readmission and Cost Burden After Robot-Assisted Radical Cystectomy.

OBJECTIVE: To examine the occurrence and cost burden of hospital readmission within 90 days of robot-assisted radical cystectomy (RARC). Subjects/Patients (or Materials) and Methods: From 2003 to 2012, 247 patients underwent RARC with extracorporeal urinary reconstruction at a single categorical cancer hospital. Continent diversions were performed in 67% of patients. All readmissions within 90 days were included. Readmissions were defined as early (<30 days) and late (31-90 days) with multiple readmissions captured as separate events. Cost analysis was performed using average direct hospital cost. The Fisher exact test was used to determine differences in proportion of readmissions between patient groups, while logistic regression was used to identify predictors for readmission. RESULTS: Ninety-eight (40%) patients were readmitted to the hospital at least once within 90 days after RARC, of which 77% occurred within 30 days. Twenty-seven (11%) required two or more readmissions. Readmissions took place at a median of 13 days after initial discharge. The most common reasons for initial readmission were infections (41%) and dehydration (19%). Stratified by urinary reconstruction type, ileal conduit (dehydration), Indiana pouch (urinary-tract infection without sepsis), and Studer neobladder (sepsis and pelvic abscess) differed by readmission reason. In a multivariable analysis, estimated blood loss was a predictor for readmission (p = 0.05). Patients readmitted to the hospital had direct costs that were 1.42× those who did not require readmission. Readmissions for ileus contributed to the highest cost of readmission, although ureteral stricture, pelvic abscess, and sepsis were the most costly per day of hospitalization. Limitations include retrospective analysis as well as variable thresholds for readmission and costs. CONCLUSIONS: Hospital readmission rates after RARC are high and costs of readmission are significant. Most patients are readmitted within 30 days and infection and dehydration are common causes. Clinicians should be aware of diversion-specific readmission causes.

The effect of nerve-sparing robot-assisted radical cystoprostatectomy on erectile function in a preoperatively potent population.

OBJECTIVE: To evaluate the effects on the potency of a bilateral cavernosal nerve-sparing approach to robot-assisted radical cystectomy (RARC) in a preoperatively potent population. PATIENTS AND METHODS: We conducted a retrospective review of 254 patients who underwent RARC between 2003 and 2012 at our single institution. We identified 33 men who were younger than 65 years and had evidence of preoperative erections on chart review. Twenty-nine of them underwent a bilateral nerve-sparing procedure, with 28 (97%) having concomitant creation of a continent urinary diversion. RESULTS: Median follow-up was 32.9 months. Postoperatively, 13 (45%) patients had documented erections sufficient for penetration with or without the use of phosphodiesterase 5 inhibitors. Additional 6 (21%) were potent with intracavernosal injections (ICI), and the remaining 10 (34%) failed ICI usage, had on-going medical issues, or lost interest in sexual activity. With univariate analysis, no significant difference was found between those who recovered erections and those who did not on a wide range of demographic, operative, and perioperative factors, including age, comorbidities, operative time, or pathologic stage. Despite neurovascular bundle preservation, there was no local cancer recurrence and no positive soft tissue margins. CONCLUSION: A cavernosal nerve-sparing robot-assisted approach to radical cystectomy allows for recovery of potency without sacrificing oncologic outcomes even with higher risk disease as compared to historical open or laparoscopic series. Further studies are required to help elucidate why some men have better recovery in this setting than others.

Intermediate-term oncologic outcomes of robot-assisted radical cystectomy for urothelial carcinoma.

PURPOSE: To evaluate intermediate-term oncologic outcomes in a large series of patients who were treated with robot-assisted radical cystectomy (RARC) for urothelial carcinoma of the bladder (UCB). PATIENTS AND METHODS: Between 2004 and 2010, 162 patients underwent RARC at City of Hope Cancer Center for UCB and were analyzed with respect to overall (OS), disease-specific (DSS), and disease-free survival (DFS). Descriptive statistics were used to summarize demographics and perioperative variables. The Kaplan-Meier method was used to estimate survival and recurrence. Univariable and multivariable Cox proportional hazards regression models were used to determine predictors of survival. RESULTS: Median follow-up was 52 months. Thirty-eight (23.4%) patients received neoadjuvant chemotherapy before RARC; 28% of patients were pT2 and 33% had final pathology status of pT3 or pT4. Median lymph node count was 28, and positive surgical margin rate was 4.3%. Local recurrence occurred in 11 (6.8%) patients. OS, DFS, and DSS at 3 years were 61%, 76%, and 83%, respectively. OS, DFS, and DSS at 5 years were 54%, 74%, and 80%, respectively. Predictors of OS and DFS on multivariable analysis were lymph node density, pathologic stage, and age-adjusted Charlson Comorbidity Index, while receipt of transfusion was also a negative predictor of OS. CONCLUSIONS: RARC provides an effective means of treatment of UCB in a minimally invasive fashion with comparable oncologic outcomes to that reported in the literature of open procedures.