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Purpose: To study the feasibility/toxicity of urethral stenting with the Memokath ® 028SW stent in patients under going prostate implant (PI) for prostate adenocarcinoma. Material and methods: An Investigational Device Exemption from the Food and Drug Administration (FDA) and institutional review board (IRB) approval were obtained. Twenty patients enrolled. Baseline American Urological Association (AUA) score was obtained prior to PI. Follow-up information was obtained with weekly phone calls for the first 12 weeks and biweekly calls for the next 12 weeks to assess toxicity and AUA score. Removal of the stent was planned at six months after PI, or earlier due to excessive toxicity/patient request. Results: Median age was 66.5 years. The median prostate volume was 39 cc (range: 10-90). The median baseline AUA score was 7.5 (range: 1-21). Three patients required intermittent self-catheterization (ISC) within 3 days after PI. No patients required ISC beyond day 3 after PI. The median duration of ISC was 1 day (range: 1-2). AUA scores returned to baseline values 6 weeks after PI. The week 6 AUA score was 10 (range: 4-16). Seven patients (35%) underwent early removal because of patient preference. The reasons were: incontinence ( n= 3), discomfort ( n= 2), hematuria ( n= 1), and obstructive symptoms ( n= 1). The median time of stent removal in these patients was 13.9 weeks (range: 0.9-21.4). Thir teen patients (65%) had ISC and/or urinary catheterization post stent removal. Median time for ISC use was 10 days (range: 1-90). Conclusions: Urethral stenting with Memokath ® in patients undergoing PI was feasible, but resulted in relatively high rate of urinary incontinence and discomfort. Given the adverse effects experienced by patients of this study, fur ther studies should focus only on patients with highest risk of urinary obstruction from PI or those with obstruction needing ISC. J Contemp Brachyther 2011; 3, 1: 18-22 DOI: 10.5114/jcb.2011.21038

Treatment decisions regarding the use of retroperitoneal lymph node dissection (RPLND) for low-stage and advanced testicular cancer may be influenced by the morbidity of the procedure. We sought to compare the complication profile of primary (P-) and post-chemotherapy (PC-) RPLND using a standardized complication grading scale.A retrospective analysis was conducted of 112 and 96 patients who underwent P-RPLND and PC-RPLND, respectively, between 1982 and 2007 for perioperative outcomes and late complications. Postoperative complications were graded using a 5-tiered scale based on the severity and/or level of intervention required for resolution.P-RPLND patients had rates of 5%, 24%, and 7% for intraoperative, postoperative, and late complications, respectively. For PC-RPLND, these rates were 12%, 32%, and 7%, respectively (P = 0.11, 0.19, and 1, respectively). Major postoperative complications (grades III-V) were observed in 3 (3%) P-RPLND and 8 (8%) PC-RPLND patients (P = 0.15), including 1 fatal pulmonary embolus in a PC-RPLND patient. Ileus accounted for 63% and 45% of postoperative complications of P-RPLND and PC-RPLND, respectively. PC-RPLND was associated with significantly greater operative times, blood loss, and transfusion rates (P0.001). Compared with PC-RPLND after first-line chemotherapy for advanced NSGCT, there were no significant differences in perioperative outcomes for PC-RPLND performed in other settings.P-RPLND and PC-RPLND are associated with low rates of serious short- and long-term complications and negligible mortality, without significant differences between the 2 procedures. The safe morbidity profile of RPLND performed by fellowship-trained urologic oncologists should be considered during treatment decision-making for low-stage and advanced testicular cancer.

470Background: Trimodality therapy with TURBT followed by concurrent chemoradiation is an alternative to cystectomy in selected patients with muscle invasive BCa. Identifying genetic determinants o...

Importance Prostate cancer with adverse pathological features (ie, pT3 and/or positive margins) after prostatectomy may be managed with adjuvant radiotherapy (ART) or surveillance followed by early-salvage radiotherapy (ESRT) for biochemical recurrence. The optimal timing of postoperative radiotherapy is unclear. Objective To compare the clinical outcomes of postoperative ART and ESRT administered to patients with prostate cancer with adverse pathological features. Design, Setting, and Participants This multi-institutional, propensity score–matched cohort study involved 1566 consecutive patients who underwent postprostatectomy ART or ESRT at 10 US academic medical centers between January 1, 1987, and December 31, 2013. Propensity score 1-to-1 matching was used to account for covariates potentially associated with treatment selection. Data were collected from January 1 to September 30, 2016. Data analysis was conducted from October 1, 2016, to October 21, 2017. Main Outcomes and Measures Freedom from postirradiation biochemical failure, freedom from distant metastases, and overall survival. All outcomes were measured from date of surgery to address lead-time bias. Results Of 1566 patients, 1195 with prostate-specific antigen levels of 0.1 to 0.5 ng/mL received ESRT and 371 patients with prostate-specific antigen levels lower than 0.1 ng/mL received ART. The median age (interquartile range) was 60 (55-65) years. After propensity score matching, the median (interquartile range) follow-up after surgery was similar between the ESRT and ART groups (73.3 [44.9-106.6] months vs 65.8 [40-107] months; P = .22). Adjuvant RT, compared with ESRT, was associated with higher freedom from biochemical failure (12-year actuarial rates: 69% [95% CI, 60%-76%] vs 43% [95% CI, 35%-51%]; effect size, 26%), freedom from distant metastases (95% [95% CI, 90%-97%] vs 85% [95% CI, 76%-90%]; effect size, 10%), and overall survival (91% [95% CI, 84%-95%] vs 79% [95% CI, 69%-86%]; effect size, 12%). Adjuvant RT, lower Gleason score and T stage, nodal irradiation, and postoperative androgen deprivation therapy were favorable prognostic features on multivariate analysis for biochemical failure. Sensitivity analysis demonstrated that the decreased risk of biochemical failure associated with ART remained significant unless more than 56% of patients in the ART group were cured by surgery alone. This threshold is greater than the estimated 12-year freedom from biochemical failure rate of 33% to 52% after radical prostatectomy alone, as determined by a contemporary dynamic nomogram. Conclusions and Relevance Adjuvant RT, compared with ESRT, was associated with reduced biochemical recurrence, distant metastases, and death for high-risk patients, pending prospective validation. These findings suggest that a greater proportion of patients with prostate cancer who have adverse pathological features may benefit from postprostatectomy ART rather than surveillance followed by ESRT.

The Bladder Cancer Think Tank III brought together a multidisciplinary group of clinician scientists, patient advocates, representatives from the National Cancer Institute, and Industry leaders to discuss the current state of the field in urothelial cancer and to develop strategies to move forward. This paper summarizes the session devoted to prevention. Experts sought to define primary, secondary, and tertiary prevention and discussed clinical trials performed to date testing retinoids, difluoromethylornithine, celecoxib, and other oral agents in a tertiary prevention setting following transurethral resection with or without intravesical therapy. Urologists practice tertiary prevention in the form of intravesical therapy, and strategies were discussed to identify biomarkers, including urinary cytokines and pathway single nucleotide polymorphism analysis associated with response to treatment. Optimizing delivery of intravesical chemotherapy to the target tissue with simple pharmacologic manipulations or packaging drugs in nanoparticles may improve treatment outcome. Defining a premalignant lesion should be a focus of future research as a strategy for early detection and secondary prevention. Cigarette smoking is the most prevalent risk factor for urothelial cancer, and emphasis was placed on smoking cessation as a powerful tool to reduce the burden of urothelial cancer, and the central role physicians must play in educating patients and providing resources. There is a strong need for research to develop markers of disease initiation and progression. These markers, combined with histories of environmental exposure to bladder carcinogens, may provide a tool to identify patients who will benefit from primary prevention.

Importance The optimal treatment for Gleason score 9-10 prostate cancer is unknown. Objective To compare clinical outcomes of patients with Gleason score 9-10 prostate cancer after definitive treatment. Design, Setting, and Participants Retrospective cohort study in 12 tertiary centers (11 in the United States, 1 in Norway), with 1809 patients treated between 2000 and 2013. Exposures Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy, or EBRT plus brachytherapy boost (EBRT+BT) with androgen deprivation therapy. Main Outcomes and Measures The primary outcome was prostate cancer–specific mortality; distant metastasis-free survival and overall survival were secondary outcomes. Results Of 1809 men, 639 underwent RP, 734 EBRT, and 436 EBRT+BT. Median ages were 61, 67.7, and 67.5 years; median follow-up was 4.2, 5.1, and 6.3 years, respectively. By 10 years, 91 RP, 186 EBRT, and 90 EBRT+BT patients had died. Adjusted 5-year prostate cancer–specific mortality rates were RP, 12% (95% CI, 8%-17%); EBRT, 13% (95% CI, 8%-19%); and EBRT+BT, 3% (95% CI, 1%-5%). EBRT+BT was associated with significantly lower prostate cancer–specific mortality than either RP or EBRT (cause-specific HRs of 0.38 [95% CI, 0.21-0.68] and 0.41 [95% CI, 0.24-0.71]). Adjusted 5-year incidence rates of distant metastasis were RP, 24% (95% CI, 19%-30%); EBRT, 24% (95% CI, 20%-28%); and EBRT+BT, 8% (95% CI, 5%-11%). EBRT+BT was associated with a significantly lower rate of distant metastasis (propensity-score-adjusted cause-specific HRs of 0.27 [95% CI, 0.17-0.43] for RP and 0.30 [95% CI, 0.19-0.47] for EBRT). Adjusted 7.5-year all-cause mortality rates were RP, 17% (95% CI, 11%-23%); EBRT, 18% (95% CI, 14%-24%); and EBRT+BT, 10% (95% CI, 7%-13%). Within the first 7.5 years of follow-up, EBRT+BT was associated with significantly lower all-cause mortality (cause-specific HRs of 0.66 [95% CI, 0.46-0.96] for RP and 0.61 [95% CI, 0.45-0.84] for EBRT). After the first 7.5 years, the corresponding HRs were 1.16 (95% CI, 0.70-1.92) and 0.87 (95% CI, 0.57-1.32). No significant differences in prostate cancer–specific mortality, distant metastasis, or all-cause mortality (≤7.5 and >7.5 years) were found between men treated with EBRT or RP (cause-specific HRs of 0.92 [95% CI, 0.67-1.26], 0.90 [95% CI, 0.70-1.14], 1.07 [95% CI, 0.80-1.44], and 1.34 [95% CI, 0.85-2.11]). Conclusions and Relevance Among patients with Gleason score 9-10 prostate cancer, treatment with EBRT+BT with androgen deprivation therapy was associated with significantly better prostate cancer–specific mortality and longer time to distant metastasis compared with EBRT with androgen deprivation therapy or with RP.

439 Background: Micropapillary UC remains rare yet with an aggressive phenotype. Limited data exists regarding the optimal management of this variant in the contemporary era. Methods: A retrospective analysis was performed to identity patients (pts) with micropapillary UC at the Cleveland Clinic (1997-2017). Demographic, clinico-pathological, treatment regimens, and clinical outcomes, e.g. progression-free and overall survival (PFS and OS) data were collected. Results: A total of 102 pts with median age 70.5 (46-90) at diagnosis, 84%, men, 17% never smokers were identified. Stage at diagnosis for 68 pts with available data was T1 in 29, T2 in 36, T3 in 1, T4 in 2, N+ in 5, and M+ in 4 pts, respectively. Twelve pts were initially treated with intravesical therapy for NMIBC with 58% progressing to higher stage. Overall, 81% of pts had cystectomy; of those 19% had neoadjuvant chemotherapy (NAC; 81% cisplatin-based, median 3 cycles), 21 pts received adjuvant chemotherapy and 3 pts adjuvant radiation. Of 12 pts with available data, 4 had down-staging with NAC with 1 pCR. Pathologic stage was 0is, I, II, III, IV in 4%, 10%, 9%, 9%, and 67% respectively. Overall, 61 pts had recurrent or de-novo metastatic disease (most nodal/local-regional recurrence). For patients with recurrence post-surgery (n = 31), 35% received systemic chemotherapy, 16% had salvage surgery, 10% had salvage radiation, 19% had best supportive care, and the rest were lost to follow-up or refused treatment. The most common 1st-line regimen included platinum-doublet (46%), other combinations (23%), single-agent (23%) and immune checkpoint inhibitors (8%). Overall response (CR/PR) to 1st-line treatment was 38% and median PFS was 8 months (95%CI 0-16.4). Overall, 29 pts died with recurrent/metastatic disease with a median OS (from time of diagnosis) of 39.3 months (95%CI 28.4-50.2) Median OS (from time of diagnosis) for pts treated with cystectomy was 47.1 months (95%CI 23.9-50.2). Conclusions: Micropapillary UC was associated with advanced pathologic stage at cystectomy and limited use of NAC. Responses were noted with NAC and 1st line systemic treatment. Further validation can assist in prognostication and selection/stratification in future trials.

457 Background: Neoadjuvant chemotherapy (NAC) is infrequently administered to patients with upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy or segmental ureterectomy and its impact on pathologic outcomes unclear. We examine pathologic outcomes in patients with UTUC receiving NAC before extirpative surgery using a population-based cancer registry. Methods: Patients who underwent extirpative surgery for UTUC from 2006-2014 were identified from the National Cancer Database. Among patients with available clinicopathologic data, the incidence of pathologic down-staging, defined as a lesser pathologic compared to clinical stage, was compared between patients who did and did not receive NAC. A multivariable model was developed to identify predictors of pathologic down-staging. Results: 7,244 patients were identified with non-metastatic UTUC who underwent extirpative surgery in the study period. 260 patients (3.6%) received NAC, with the use of NAC increasing over time from 2.0% patients in 2006 to 7.1% of patients in 2014 (linear trend p < 0.001). Clinical and pathologic staging data were available for 119 and 2904 patients who did and did not receive NAC, respectively. Thirty patients (25.2%) who received NAC experienced pathologic down-staging, compared to 52 patients (1.8%) who did not receive NAC (p < 0.0001). On multivariable analysis, NAC was associated with a higher likelihood of pathologic down-staging (OR 10.2, 95% CI 5.4-19.3). Additional predictors of pathologic down-staging include a higher clinical T stage (p = 0.001) and African-American race (OR 2.7, 95% CI 1.1-6.6). Compared to renal pelvis UTUC, ureteral UTUC was associated with a similar likelihood of pathologic down-staging (OR 1.5, 95% CI 0.9-2.5). Conclusions: NAC is infrequently used among patients with UTUC undergoing extirpative surgery. A higher incidence of pathologic down-staging was observed among patients receiving NAC. These findings suggest clinical benefit of NAC with respect to pathologic outcomes in patients with UTUC and may help guide selection of patients for NAC prior to radical surgery until data from prospective studies becomes available.

88 Background: Management of HRPCa is a clinical challenge. Novel AR inhibitors could potentially impact outcome in HRPCa men following RP. We conducted a phase II study evaluating the efficacy/safety of Enza in men with HRPCa following RP. Methods: HRPCa pts (≥pT3a, GS≥8, iPSA ≥20 ng/mL, +ve lymph nodes (LN), or ≥35% chance of biochemical recurrence (BCR) at 5 yrs based on MSKCC’s nomogram) with undetectable PSA within 3 months from RP were eligible. Enza 160mg PO daily was given in 28-day cycles until disease progression, intolerability, consent withdrawal, or study completion at 24 months. Accrual goal was N=40 to provide 80% power to detect a 75% decrease in the risk of BCR from historical 55% rate. BCR was defined as PSA ≥0.2ng/mL on 2 consecutive lab results or any PSA rise that resulted in subsequent therapy. Results: 42 men enrolled. Median age 59 (range 43-70), based on biopsy 45% were GS7; 36% GS8, 19% GS9. 76% men had cT1, 24% cT2, median iPSA was 8.2 (range 2-77). On prostatectomy pathology: 50% had pT3b; 52% +ve margins; 50% SVI; 24% had +LN. 37 (88%) pts completed 24 planned cycles. Of the 5 pts who did not complete all cycles, 3 withdrew consent for toxicity (2 had G3 fatigue, 1 had G3 fatigue and arthralgias/myalgias), 1 had rising PSA requiring subsequent therapy, and 1 had financial concerns. With median follow-up of 31 months (range 2.5-44.5), 37 (88%) pts remain free of BCR. Of the 5 pts who developed BCR, 4 completed all 24 months on therapy. Median time to BCR was 31 months (range 13-40). Most common adverse events (AE) are listed (Table). Conclusions: Adjuvant Enza in men with HRPCa following RP is safe and relatively well-tolerated. Long-term safety, efficacy, and genomic correlations (including tumor RNA expression) are ongoing. Clinical trial information: NCT01927627. [Table: see text]

446 Background: Cisplatin-based NAC followed by radical cystectomy is the standard of care in MIBC but many pts are cisplatin-unfit. Data in pts with low glomerular filtration rate (GFR) who receive cisplatin-based NAC is limited. Methods: A retrospective analysis of pts who received cisplatin-based NAC at Cleveland Clinic (2005-2016) was conducted. Pts with pre-NAC GFR < 60 ml/min by either CG or MDRD formula (low GFR; N = 30) were compared to pts with GFR ≥60 (normal GFR; N = 94) in terms of NAC tolerability and outcomes including pathologic complete (pCR, pT0N0) and partial response (pPR, < pT2N0). A secondary analysis compared 3 groups of pts: GFR < 50ml/min (N = 10), GFR 50-59 ml/min (N = 20), and GFR ≥60 (N = 94). Results: Low GFR pts were older (median age 71 vs 65, p < 0.001) and had higher rates of hydronephrosis (33% vs 15%, p = 0.03). ECOG PS, other demographic and TURBT features (stage, LVI, CIS) did not differ significantly. Low GFR pts were more likely to receive gemcitabine/cisplatin (83% vs 71%, p = 0.04) and get split-dose cisplatin (38% vs 16%, p = 0.02). Split-dose cisplatin use in low GFR pts did not impact NAC tolerability or outcomes. NAC cycles completed (median 3 per group) were comparable, and most low GFR pts (70%) completed intended NAC regimen. Low GFR pts were more likely to have early NAC discontinuation (30% vs 13%, p = 0.03) and NAC modification (delay, dose reduction, discontinuation) (66% vs 40%, p = 0.02). No differences were seen in cystectomy completion rate (93% per group), time to cystectomy, length of stay, surgical complications, and GFR change from baseline. Combined pCR/pPR was higher in normal GFR group (54% vs 25%, p = 0.01). Among pts with very low GFR ( < 50 ml/min), 60% completed intended NAC regimen and 70% had NAC modification. Rates of pCR and pPR were low: 0% and 12%, respectively. Conclusions: Low GFR pts were older, had more NAC discontinuations/modifications and lower pCR/pPR rate, but most completed planned NAC cycles. Relative to normal GFR pts, low GFR pts were not prevented or delayed in getting cystectomy, and had comparable impact of NAC on GFR. For carefully selected pts with GFR < 60 ml/min, cisplatin-based NAC is a treatment option, consistent with prior data.

24 Background: The use of radical prostatectomy (RP) as initial treatment of high-risk/locally-advanced prostate cancer is increasing but patients (pts) with adverse pathologic features such as positive surgical margins or T3 disease have up to 70% recurrence risk. These high-risk pts may be managed with adjuvant radiotherapy (ART) or early salvage radiotherapy (ESRT). The optimal timing of post-operative radiotherapy is unclear. Methods: Individual data from 1566 consecutive pts with pT2N0M0/R1 or pT3N0M0/R0-1 disease who underwent post-prostatectomy ART or ESRT (1987-2013) at 10 academic centers were pooled. Post-irradiation freedom from biochemical failure (FFBF), freedom from distant metastases (FFDM), prostate-cancer specific survival (PCSS), and overall survival (OS) were compared using Kaplan-Meier and multivariate competing-risks regression (MVA) analyses. Propensity score (PS) matching was used to account for covariates potentially associated with treatment allocation. All outcomes were measured from the date of surgery to address lead time bias. Results: After PS-matching, median follow-up after surgery was 66 vs. 73 months for the ART and ESRT groups, respectively, and baseline characteristics were well-matched. ART was associated with higher FFBF (12-yr: 69% vs. 43%; log-rank P < 0.0001), FFDM (12-yr: 95% vs. 85%; log-rank P = 0.03), PCSS (12-yr: 99% vs. 94%; log-rank P = 0.048), and OS (12-yr: 91% vs. 79%; log-rank P = 0.01). ART, lower Gleason score, lower T-stage, nodal irradiation, and postoperative androgen deprivation therapy were favorable prognostic features on MVA for BF. Sensitivity analysis demonstrated that the decreased risk of BF associated with ART remained significant unless more than 56% of ART pts were cured by surgery alone. This threshold is greater than the estimated 12-yr FFBF of 46% after RP alone as determined by a contemporary nomogram. Conclusions: To the best of our knowledge, this represents the largest multi-institutional study to date comparing ART to ESRT. ART was associated with reduced biochemical recurrence, distant metastases, and death compared to ESRT for high-risk pts, pending prospective validation.

TPS155 Background: The common germline variant HSD3B1(1245C) encodes for a gain-of-function in 3βHSD1 which is associated with a shorter duration of response to androgen deprivation therapy (ADT) and more rapid disease progression to castration resistant PCa (CRPC) as shown previously in 5 independent cohorts. Therefore, evaluating the effect of such genotype variation on the level of steroid metabolites and the intratumoral dihydrotestosterone (DHT) concentration in benign and tumor tissue of men on ADT is of significant importance. We hypothesize that patients with homozygous HSD3B1 (1245C) genotype (HZ) will have a sustained androgen synthesis from extragonadal precursor steroids and higher concentrations of DHT compared to patients with wild-type HSD3B1 (1245A) (WT) inheritance in the context of testosterone suppression. In addition, it is expected that heterozygous HSD3B1 (1245C) patients (HTZ) will have intermediate levels of DHT. We also hypothesize that treatment with androgen receptor (AR) antagonist (apalutamide) will reverse the effects of elevated DHT on AR signaling in benign and malignant prostate tissue. Methods: In this Phase II trial (NCT02770391), men with newly diagnosed intermediate or high-risk PCa (GS ≥ 4+3, ≥cT2b, or PSA ≥ 10) who are scheduled to undergo radical prostatectomy (RP) will be enrolled into 3 groups based on their HSD3B1 genotype. All pts will receive one dose of 7.5 mg leuprolide injection and apalutamide 240 mg/day orally for 28 ± 3 days prior to RP. DHT and 7 other androgens (including testosterone, Dehydroepiandrosterone, Androstenedione) will be evaluated in the normal and malignant prostate tissue as well as serum samples obtained at the time of RP. AR regulated genes expression (including PSA, FKBP5, TMPRSS2) will be compared across 3 genotypes. A sample size of 57 pts (WT = 30, HTZ = 15, HZ = 12) will allow a statistical power of > 80% (with two-sided α = 0.05) to detect a 4-fold trend in DHT concentrations in the resected prostate tissue (primary endpoint) as well as similar trend in other androgens (secondary endpoint). As of Oct 2017, 16 of planned 57 pts have been enrolled. Clinical trial information: NCT02770391.

65 Background: While androgen deprivation therapy (ADT) is a common form of systemic therapy for treating high-risk prostate cancer (HRCaP), distant metastases development remains the predominate form of failure. We present a description of the sites of failure after treatment of HRCaP with External Beam Radiation (EBRT), I-125 Brachytherapy (PB), or Radical Prostatectomy (RP). This is accompanied by an analysis of prostate cancer-specific mortality (PCSM) after clinical failure. Methods: The study includes 2186 patients with HRCaP according to NCCN guidelines (684 EBRT, 409 PB, and 1093 RP). The association of PCSM with clinical and pathologic variables was assessed with Fine and Gray regression with non-PCSM mortality treated as a competing event. Results: The median f/u is 52 months. Overall, there were 323 clinical failures (sites of first failures: 287 distant (DM), 34 local (LF), 2 DM + LF). The median time to the diagnosis of DM was 44 months. ADT was used in 93% of EBRT, 53% of PB and 19% of RP patients. Further details regarding the development of DM is shown in Table 1. The type of initial treatment was not associated with PCSM after DM (Table 1). The only factor significantly associated with PCSM was Gleason Score (p = 0.0372). Conclusions: DM is the primary mode of failure after definitive treatment of HRCaP. The type of initial definitive treatment did not affect PCSM after DM. The cure rates of all forms of definitive treatment of HRCaP would benefit from better systemic therapy. [Table: see text]

452 Background: Increased DLL3 expression (exp) and small cell % (SC%) were found in prior analyses to predict worse outcomes in SCBC. Assessment of gene and protein exp of other Notch pathway and neuroendocrine (NE) markers, such as ASCL1 and CD56, can help with prognostication and treatment target identification in SCBC. Methods: Among 63 patients (pts) with biopsy-confirmed SCBC seen at Cleveland Clinic (1993-2015), 52 had tissue available for IHC analysis of tumor biomarkers: DLL3, PD-L1, ASCL1 and CD56. All pts had clinical and outcomes data, and had SC% quantified by central path review. A subset of 39 pts had gene exp analysis using HTG EdgeSeq OBP assay. Correlations among biomarkers, between biomarkers and pt characteristics as well as gene exp were assessed. Multivariate analyses (MVA) were used to identify predictors of overall (OS) and progression-free survival (PFS). Results: In the 52 pt cohort, median age was 71, 83% were men, 39% had LN+ disease, and 79% had SC% > 50%. Protein exp ( > 1% of tumor cells) of DLL3, PD-L1, ASCL1 and CD56 was noted in 68%, 30%, 52% and 81% of pts, respectively. ASCL1 protein exp correlated with protein exp of DLL3 (r = 0.73, p < .0001), CD56 (r = 0.35, p = .01), and SC% (r = 0.34, p = .01) and correlated with gene exp of several Notch genes and NE markers: DLL3, DLL4, Notch1, CHGA (p < .05 for all). CD56/NCAM1 protein exp correlated with DLL3 protein exp (r = 0.32, p = .02) and with SC% (r = 0.26, p = .06) and with gene exp of DLL4, Notch1, SYP and NCAM1 (p < .05 for all). In MVA, increased CD56 protein exp ( > 30%) was associated with shorter OS (HR: 2.23; 95%CI 1.06-4.70, p = .03) and PFS (HR: 2.07; 95%CI 1.02-4.20, p = .04). Pts with low protein exp of both CD56 (≤30%) and DLL3 (≤10%) had longer median OS (103.4 vs 18.4 months, p = .01) and PFS (92.2 vs 11.4 months, p = .02) relative to pts with high protein exp of either biomarker. Conclusions: Most SCBC tumors expressed CD56, and increased exp predicted shorter OS and PFS, findings similar to those reported for DLL3. Low concurrent exp of both CD56 and DLL3 proteins was associated with better outcomes. Strong correlation of CD56/NCAM1 gene and protein exp suggests that its regulation may be at the transcriptional level. Gene exp signature prognostic of outcomes is currently being pursued in SCBC.

Prostate cancer is an appropriate target for primary chemoprevention because of its ubiquity, disease-related mortality, treatment-related morbidity, and long latency period. The PCPT and REDUCE trials demonstrate that this cancer can be prevented by a relatively nontoxic oral pharmacologic agent (5alpha-reductase inhibitors). Evidence from the SELECT trial argues against the recommendation of the use of vitamins and micronutrients as chemoprevention of prostate cancer. Dietary modification may substantially alter a man's risk of prostate cancer, but the specific dietary manipulations that are necessary are poorly defined and these may need to be instituted in early adulthood to be successful. 5alpha-reductase inhibitors represent an effective primary prevention strategy, and these agents should be used more liberally for the prevention of prostate cancer, particularly in high-risk patients.

OBJECTIVES To assess the relationship between prostate-specific antigen (PSA) testing frequency and biochemical failure (bF) and clinical failure (cF). METHODS The records of 5616 patients with low-, intermediate-, or high-risk prostate cancer treated (brachytherapy, external beam radiotherapy, or surgery) between 1996 and 2007 were reviewed. Factors influencing bF and cF were recorded including age, initial PSA, androgen deprivation, race, clinical stage, biopsy Gleason score, and the frequency of follow-up PSA testing. Univariate and multivariate analyses were performed to assess the effect of these factors on bF and cF. Sensitivity and specificity were calculated to determine the optimal frequency of PSA testing. RESULTS The median follow-up is 45 months. The median number of PSA tests per year before the occurrence of bF and cF is 1.9 for both endpoints. The multivariate analysis of factors significantly associated with bF and cF demonstrate that PSA frequency, initial PSA, clinical stage, and biopsy Gleason score are independently predictive of outcome. PSA testing achieves the best sensitivity and specificity when 2 PSA tests are drawn per year for both bF (sensitivity = 66.3%, specificity = 58.0%) and cF (sensitivity = 75.1%, specificity = 60.3%). CONCLUSIONS The frequency of PSA testing is strongly associated with the detection of bF and cF. Because it is a variable that can be controlled, PSA testing frequency should be standardized to minimize spurious conclusions from studies with bF and cF endpoints. The sensitivity and specificity can be optimized by obtaining 2 PSA tests per year.

Purpose There is equipoise regarding the optimal treatment of clinical stage (CS) I nonseminomatous germ cell testicular cancer (NSGCT). Formal mechanisms that enable patients to consider cancer outcomes, treatment-related morbidity, and personal preferences are needed to facilitate decision making between retroperitoneal lymph node dissection (RPLND), primary chemotherapy, and surveillance. Methods Decision analysis was performed using a Markov model that incorporated likelihoods of survival, treatment-related morbidity, and utilities for seven undesired post-treatment health states to estimate the quality-adjusted survival (QAS) for each treatment option. Utilities were obtained from 24 hypothetical NSGCT patients using a visual analog (rating) scale and standard gamble. Results Overall, QAS associated with each treatment was high and differences in QAS were small. Surveillance was the preferred intervention for patients with a risk of relapse less than 33% and 37% using the rating scale and standard-gamble method of utility assessment, respectively. Active treatment was favored over surveillance for patients with relapse risk on surveillance greater than 33% and 37% by the rating scale (RPLND preferred) and standard-gamble methods (primary chemotherapy preferred), respectively. Substantial differences in average utilities were seen depending on the method used. By the rating scale, patients substantially devalued life in six of seven undesired health states but they were surprisingly tolerant of treatment-related morbidity using standard gamble. Conclusion A decision model has been developed for CS I NSGCT that estimates QAS for RPLND, primary chemotherapy, and surveillance by considering cancer outcomes, morbidity, and patient preferences. Surveillance was the preferred intervention for all except those patients at high risk for relapse.

Bladder cancer has a remarkably variable natural history. Noninvasive, low-grade (TaLG) lesions have a propensity to recur but pose little threat to the patient's longevity. Non-muscle-invasive, high-grade (Ta-TIS-T1HG) lesions can be effectively treated with intravesical BCG, but a subset may progress to muscle-invasive and metastatic bladder cancer. Muscle-invasive cancers (T2-T3) are uniformly lethal if inadequately treated, and subsets of patients benefit from perioperative chemotherapy and some may be adequately treated with bladder preservation strategies. The ability to accurately predict this variable natural history is essential to optimize treatment. At each stage of disease, the prognosis is often influenced by multiple parameters (e.g., tumor grade and stage, age, comorbidity) and treatments (e.g., radical cystectomy vs. BCG), and different endpoints are relevant based on the stage of disease (recurrence for TaLG, progression for Ta-TIS-T1HG, survival for T2-T4a). Historically, prediction of these endpoints for decision-making has been accomplished with physician judgment and/or basic decision aids such as risk classification systems. However, such methods of risk estimation are unable to fully account for the complex tumor biology and behavior of bladder cancer, potentially leading to inaccurate predictions and inappropriate treatment assignment. Nomograms are capable of incorporating multiple variables and generating accurate risk estimates tailored to the individual patient which may greatly facilitate patient counseling and treatment selection. Although their use has become more widespread, bladder cancer nomograms remain a relatively nascent field of study, and further development of novel nomograms that can account for all clinical stages of bladder cancer is needed.

Positive surgical margins increase the risk of biochemical recurrence after radical prostatectomy by 2 to 4-fold. The risk of biochemical recurrence may be influenced by the anatomical location and extent of positive surgical margins. In a multicenter study we analyzed the predictive usefulness of several subclassifications of positive surgical margins.The clinical information and followup data of 7,160 patients treated with radical prostatectomy alone at 1 of 3 institutions between 1995 and 2006 were modeled using Cox proportional hazards regression analysis for biochemical recurrence. Positive surgical margins were analyzed as solitary vs multiple, focal vs extensive and apical location vs other. The usefulness of these subclassifications was assessed by the improvement in predictive accuracy of nomograms containing these parameters compared to one in which the surgical margin was modeled simply as positive vs negative.The 7-year progression-free probability was 60% in patients with positive surgical margins. A positive surgical margin was significantly associated with biochemical recurrence (HR 2.3, p0.001) after adjusting for age, prostate specific antigen, pathological Gleason score, pathological stage and year of surgery. An increased risk of biochemical recurrence was associated with multiple vs solitary positive surgical margins (adjusted HR 1.4, p = 0.002) and extensive vs focal positive surgical margins (adjusted HR 1.3, p = 0.004) on multivariable analysis. However, neither parameter improved the predictive accuracy of a nomogram compared to one in which surgical margin status was modeled as positive vs negative (concordance index 0.851 vs 0.850 vs 0.850).The number and extent of positive surgical margin significantly influence the risk of biochemical recurrence after radical prostatectomy. However, the empirical prognostic usefulness of subclassifications of positive surgical margins is limited.

Purpose The long-term risk of prostate cancer–specific mortality (PCSM) after radical prostatectomy is poorly defined for patients treated in the era of widespread prostate-specific antigen (PSA) screening. Models that predict the risk of PCSM are needed for patient counseling and clinical trial design. Methods A multi-institutional cohort of 12,677 patients treated with radical prostatectomy between 1987 and 2005 was analyzed for the risk of PCSM. Patient clinical information and treatment outcome was modeled using Fine and Gray competing risk regression analysis to predict PCSM. Results Fifteen-year PCSM and all-cause mortality were 12% and 38%, respectively. The estimated PCSM ranged from 5% to 38% for patients in the lowest and highest quartiles of predicted risk of PSA-defined recurrence, based on a popular nomogram. Biopsy Gleason grade, PSA, and year of surgery were associated with PCSM. A nomogram predicting the 15-year risk of PCSM was developed, and the externally validated concordance index was 0.82. Neither preoperative PSA velocity nor body mass index improved the model's accuracy. Only 4% of contemporary patients had a predicted 15-year PCSM of greater than 5%. Conclusion Few patients will die from prostate cancer within 15 years of radical prostatectomy, despite the presence of adverse clinical features. This favorable prognosis may be related to the effectiveness of radical prostatectomy (with or without secondary therapy) or the low lethality of screen-detected cancers. Given the limited ability to identify contemporary patients at substantially elevated risk of PCSM on the basis of clinical features alone, the need for novel markers specifically associated with the biology of lethal prostate cancer is evident.

The development of targeted agents for renal cell carcinoma has renewed interest in consolidative surgery due to the robust clinical responses seen with these agents. The integration of targeted therapy and surgery requires careful consideration due to the potential for increased perioperative morbidity.We retrospectively identified patients with renal cell carcinoma treated with sunitinib, sorafenib or bevacizumab plus interleukin-2 before tumor resection.Between June 2005 and August 2008, 19 patients were treated with targeted therapy and subsequently underwent resection. Surgical extirpation involved an open and a laparoscopic approach in 18 and 3 cases, respectively, for locally advanced (8), locally recurrent (6) and metastatic disease (3). Two patients with extensive bilateral renal cell carcinoma were also treated to downsize the tumors to enable partial nephrectomy. Perioperative complications were noted in 16% of patients. One patient had a significant intraoperative hemorrhage and disseminated intravascular coagulopathy from a concomitant liver resection. An anastomotic bowel leak and abscess were noted postoperatively in another patient who underwent en bloc resection of a retroperitoneal recurrence and adjacent colon. Two patients (11%) had minor wound complications, including a wound seroma and a ventral hernia. Pathological analysis of 20 specimens revealed clear cell, chromophobe and unclassified renal cell carcinoma in 80%, 5% and 10% of cases, respectively. One patient (5%) had a pathological complete response.Surgical resection of renal cell carcinoma after targeted therapy is feasible with low morbidity in most patients. However, significant complications can occur, raising concern for possible compromise of tissue and/or vascular integrity associated with surgery in this setting.

OBJECTIVES To review our experience with radical nephrectomy and inferior vena cava thrombectomy (RNIVCT) to determine the utility of preoperative embolization. Preoperative embolization has been used as an adjunctive procedure to facilitate surgical resection of complex renal tumors. METHODS From 1990 to 2007, 225 patients with renal tumors and inferior vena cava thrombus underwent RNIVCT, including 135 patients who had undergone preoperative renal artery embolization and 90 patients who had not. The effect of embolization on perioperative morbidity and mortality, transfusion requirements, blood loss, and operative time was analyzed by comparing the 2 groups. RESULTS The mean primary tumor size was similar in both groups; however, 67% of the RNIVCT embolization group vs 48% of the nonembolization group had retrohepatic (level III) or supradiaphragmatic (level IV) thrombus extension (P = .032). The RNIVCT embolization patients had a greater median number of perioperative units transfused (8 vs 4; P = .001), a longer operative time (390 vs 313 minutes; P < .001), more postoperative complications (43% vs 29%; P < .001), a longer intensive care unit stay (2 vs 0.5 days), and increased perioperative mortality (13% vs 3%; P = .017). No differences were found in intraoperative complications or length of hospitalization. Multivariate analysis showed a fivefold greater risk of perioperative death (adjusted odds ratio 5.5; P = .029) and a trend toward increased blood transfusion (regression coefficient 3.9; P = .08) with preoperative embolization. CONCLUSIONS The results of our study have shown that routine preoperative renal artery embolization in patients undergoing RNIVCT does not provide any measurable benefit in reducing blood loss or complications and was associated with increased major perioperative complications and mortality.

A preoperative nomogram is an effective tool for assessing the risk of disease progression after radical prostatectomy for localized prostate cancer. To better understand the performance of nomograms for patients with a low prostate-specific antigen (PSA) level, we examined whether patients with a PSA level2.5 ng/mL had outcomes different than predicted by a validated preoperative nomogram.A cohort of 6130 patients from 2 referral centers was analyzed. Kaplan-Meier methods were used to estimate the recurrence-free probabilities stratified by PSA group (2.5 vsor=2.5 ng/mL). Cox proportional hazards regression analysis was used to evaluate whether the PSA grouping was associated with biochemical recurrence, controlling for preoperative nomogram probability.Of 6130 patients, 399 (6.5%) had a PSA level2.5 ng/mL. Patients with a PSA level ofor=0.5 ng/mL had a high rate of nonorgan-confined disease (33% vs 15% for PSA levels of 0.6-2.5 ng/mL). The median follow-up for recurrence-free patients was 2.4 years, and 10 patients with a PSA level of2.5 ng/mL and 597 patients with a PSA level2.5 ng/mL developed recurrence (total 607/6130). With adjustment for the preoperative nomogram probability, no significant difference was found in recurrence by PSA grouping (hazard ratio 0.78 for PSA2.5 vsor=2.5 ng/mL; 95% confidence interval 0.42-1.48; P = .5).Patients with a low PSA comprise a small proportion of those treated, and most have palpable disease. Patients with especially low PSA values (or=0.5 ng/mL) have a high rate of nonorgan-confined disease. We saw no evidence that patients with low PSA levels have worse outcomes, after the stage and grade were taken into account.

Adjuvant radiotherapy, surveillance, and single-agent carboplatin chemotherapy are all accepted treatment options for clinical stage (CS) I seminoma with cure rates approaching 100%. Low-dose (25-35 Gy) adjuvant radiotherapy to the retroperitoneum and ipsilateral pelvis has been the mainstay of treatment for decades and is associated with excellent long-term survival and acceptable short-term toxicity. The use of lower radiation doses (20 Gy) and the omission of pelvic radiation have been investigated to reduce toxicity. However, the risk of late toxicity (specifically cardiovascular disease and secondary malignant neoplasms) resulting from radiation exposure have diminished the appeal of this approach, particularly given the fact that 80-85% of patients are cured by orchiectomy. The appeal of surveillance is the avoidance of treatment-related morbidity in 80-85% of patients and the successful salvage of relapses with 30-35 Gy radiotherapy in most cases. However, given the prolonged time course to relapse in CS I seminoma on surveillance, long-term follow-up with frequent abdominal-pelvic imaging is required. Single-agent carboplatin is associated with comparable short-term relapse rates to adjuvant radiotherapy with the potential for decreased long-term toxicity. However, concerns about the risk of inadequate therapy and late toxicity limit the acceptance of this approach until long-term results are available. With potential of avoiding treatment-related toxicity without compromising curability and given the overall low risk of occult metastasis in clinical stage I seminoma, surveillance is the recommended treatment option. Adjuvant dog-leg radiotherapy is the preferred approach for non-compliant patients or those unwilling to go on surveillance.

Taxane based chemotherapy has activity in advanced prostate cancer but previous studies of neoadjuvant docetaxel demonstrated a prostate specific antigen response with no obvious antitumor activity. The efficacy and safety of neoadjuvant albumin-bound paclitaxel (nab-paclitaxel, Abraxane), a novel nanoparticle based formulation, were assessed in patients with high risk, locally advanced prostate cancer.Eligible patients had locally advanced prostatic adenocarcinoma, clinical stage cT2b or greater, Gleason score 8 or greater, or serum prostate specific antigen 15 ng/ml or greater without metastatic disease. Patients received 2 cycles of 150 mg/m(2) nab-paclitaxel weekly for 3 weeks during each 4-week cycle, followed by radical prostatectomy with bilateral lymphadenectomy. Efficacy assessments included pathological and prostate specific antigen response.A total of 19 patients completed neoadjuvant therapy and 18 underwent radical prostatectomy. Median pretreatment prostate specific antigen was 8.5 ng/ml and median Gleason score was 8. Despite the lack of complete pathological responses 5 of 18 patients (28%) had organ confined disease and 9 of 18 (50%) had specimen confined disease. Post-chemotherapy prostate specific antigen was decreased in 18 of 19 (95%) patients and median decrease was 2.9 ng/ml (35%, p0.001). An initial prostate specific antigen after radical prostatectomy of 0.02 ng/ml or less was achieved in 17 of 18 (94%) patients. There were no significant perioperative complications. Cytoplasmic vacuolization (focal in 10 and extensive in 7) was evident in all but 1 patient (94%). Ten patients (56%) had grade 3 and 1 had grade 4 neutropenia with no febrile neutropenia.Neoadjuvant nab-paclitaxel was well tolerated. Similar to our experience with neoadjuvant docetaxel there were no pathological complete responses, although a possible histological antitumor effect was observed.

Purpose: Many patients diagnosed with low grade and early stage prostate cancer have indolent disease and may not benefit from immediate therapy. In patients referred for biopsy following community, screening we validated the Kattan and Steyerberg nomograms for predicting indolent disease in a contemporary urological practice. Materials and Methods: A total of 296 patients who underwent prostate biopsy and radical prostatectomy at a single institution were identified for nomogram validation. All patients had clinically localized, stage T1c or T2a and biopsy Gleason score 6 prostate cancer. Clinical and biopsy pathological information was compared to surgery pathology results for nomogram validation with indolent disease defined as surgical Gleason score 6 or less, tumor volume less than 0.5 cc and organ confined disease. Nomogram performance was assessed by the ROC curve. Results: Of the patients 27.4% had pathologically indolent disease at prostatectomy. Based on pretreatment variables the Kattan and Steyerberg nomograms were able to predict indolent disease with similar discrimination levels (AUC 0.777 and 0.772, respectively). Conclusions: Two previously described nomograms performed equally well for predicting indolent disease. These data further establish the role of validated nomograms for clinical decision. making for managing screening detected prostate cancer.

Purpose Patients with clinical stage (CS) IIA and IIB nonseminomatous germ cell tumor (NSGCT) with adenopathy more than 2 cm, multiple masses, elevated serum tumor markers, or disease outside the primary landing zone have increasingly been recommended to receive primary chemotherapy over time at our institution. The impact of these selection factors on the outcome of patients managed primarily by retroperitoneal lymph node dissection (RPLND) or chemotherapy was examined. Patients and Methods Between 1989 and 2002, 252 patients with CS IIA and IIB NSGCT were referred to our institution for initial management, of whom 136 underwent RPLND and 116 received chemotherapy and postchemotherapy RPLND. Patient information was obtained from a prospective RPLND database. Results Proportionately more patients received chemotherapy over time (22% in 1989 to 1993 v 68% in 1999 to 2002), and the relapse-free survival (RFS) subsequently improved from 84% (1989 to 1998) to 98% (1999 to 2002; P = .004) without increasing the proportion who received any chemotherapy (70% v 79%; P = .16). By increasingly selecting patients with adverse features for primary chemotherapy, the RFS after RPLND improved from 78% to 100% (P = .019), but rates of pathologic stage II and retroperitoneal teratoma were unaffected. Retroperitoneal histology and RFS did not change over time for chemotherapy patients. Primary chemotherapy was associated with improved RFS compared with RPLND (98% v 79%; P < .001), but disease-specific survival did not differ significantly (100% v 98%; P = .3). Conclusion Patient selection factors have significantly improved the outcome of patients with CS IIA and IIB NSGCT without substantially increasing the proportion of patients exposed to chemotherapy.

Purpose An increasing serum prostate-specific antigen (PSA) level is the initial sign of recurrent prostate cancer among patients treated with radical prostatectomy. Salvage radiation therapy (SRT) may eradicate locally recurrent cancer, but studies to distinguish local from systemic recurrence lack adequate sensitivity and specificity. We developed a nomogram to predict the probability of cancer control at 6 years after SRT for PSA-defined recurrence. Patients and Methods Using multivariable Cox regression analysis, we constructed a model to predict the probability of disease progression after SRT in a multi-institutional cohort of 1,540 patients. Results The 6-year progression-free probability was 32% (95% CI, 28% to 35%) overall. Forty-eight percent (95% CI, 40% to 56%) of patients treated with SRT alone at PSA levels of 0.50 ng/mL or lower were disease free at 6 years, including 41% (95% CI, 31% to 51%) who also had a PSA doubling time of 10 months or less or poorly differentiated (Gleason grade 8 to 10) cancer. Significant variables in the model were PSA level before SRT (P < .001), prostatectomy Gleason grade (P < .001), PSA doubling time (P < .001), surgical margins (P < .001), androgen-deprivation therapy before or during SRT (P < .001), and lymph node metastasis (P = .019). The resultant nomogram was internally validated and had a concordance index of 0.69. Conclusion Nearly half of patients with recurrent prostate cancer after radical prostatectomy have a long-term PSA response to SRT when treatment is administered at the earliest sign of recurrence. The nomogram we developed predicts the outcome of SRT and should prove valuable for medical decision making for patients with a rising PSA level.

Purpose A persistently elevated or rising serum level of prostate-specific antigen (PSA) after radical prostatectomy is indicative of recurrent prostate cancer. The natural history of PSA-defined biochemical recurrence (BCR) is highly variable. While a rising PSA level universally antedates metastatic progression and prostate cancer-specific mortality (PCSM), it is not a surrogate for these endpoints. Thus, the management of patients with BCR is controversial. Methods A literature review was conducted to determine the incidence and natural history of BCR, prognostic factors for clinical progression (CP), and the available evidence supporting local or systemic salvage therapy for these patients. Results BCR is best defined as two successive PSA levels ≥0.4ng/ml, as this correlates most accurately with CP. PSA doubling time (PSA-DT) and prostatectomy Gleason score are the variables that best predict the development of distant metastasis and PCSM. Prognostic models based on these and other variables are useful for assessing the need for salvage therapy and the anticipated outcome following local salvage therapy. A treatment algorithm for managing patients with post-prostatectomy BCR was devised. Conclusions Management of patients with BCR after prostatectomy continues to be a complex and challenging issue. Improved methods for risk stratification allow for identification of patients who require treatment. Furthermore, these methods aid in determination of the pattern of disease recurrence, thereby guiding treatment modality. Randomized trials are essential to determine the value of local or systemic salvage therapy strategies in this patient population.

Testis cancer represents the model for a curable malignancy. Although there is consensus about the appropriate management of metastatic (clinical stage [CS] IIC-III) nonseminomatous germ cell tumor (NSGCT) in terms of the chemotherapy regimens, number of cycles, and the surgical resection of postchemotherapy residual masses, there remains controversy regarding the appropriate management of low-stage NSGCT (CSI-IIB). In this article, the benefits and drawbacks of each treatment option are reviewed; an evidence-based approach when confronted with such a patient and how to best select a treatment avenue based on the patient's clinical and pathologic features are also discussed.

Several disease characteristics have been identified as potential predictors for pathological node involvement (pN+) following radical cystectomy (RC). However, these have not been assessed in patients treated with neoadjuvant chemotherapy (NAC). We endeavored to assess factors predicting adverse pathology in clinically node-negative patients treated with NAC and RC.Patients from four North American institutions with cT2-4aN0M0 UC who received three or four cycles of NAC followed by RC were selected. Logistic regression was used to predict pN+,pT2 and pT4 disease.One hundred and ninety-six patients were included. The clinical stage was cT2 in 115 (61 %), cT3 in 62 (33 %) and cT4 in 12 (6 %) cases. NAC regiments were gemcitabine-cisplatin (GC)-4 cycles 57 (29 %), GC-3 cycles 77 (39 %), methotrexate, vinblastine, adriamycin, cisplatin (MVAC)-3 cycle 22 (11 %) and MVAC-4 cycles 40 (21 %). pN+ was seen in 35 (18 %) patients. In the logistic regression analysis, cT4 stage (OR 7.50; 95 % CI 1.58-33.3) and three compared to four cycles of GC (OR 3.44; 95 % CI 1.09-10.9) were significant predictors of pN+ status. Additionally, when controlling for clinical stage, three cycles of GC, compared to four, were significantly associated with higher rates of pT4 disease and lower rates of downstaging to non-muscle-invasive disease.The results suggest that four cycles of neoadjuvant GC may be superior to three cycles, and the latter regimen may be associated with adverse pathological findings. Although this would require validation in a prospective trial, it does encourage the completion of the conventional four cycles GC whenever possible.

INTRODUCTION AND OBJECTIVES: MR-US fusion biopsy (MR-US-FB) represents a potentially useful tool to assess for PCa progression in patients on active surveillance (AS). It is unknown whether MR-US-FB is superior to TRUS saturation biopsy to accurately characterize disease reclassification. We analyzed our initial experience with MR-US-FB compared with TRUS saturation biopsy in patients on AS. METHODS: 90 patients undergoing surveillance biopsy were analyzed. 35 patients with previously diagnosed PCa on active surveillance underwent MR-US-FB (UroNav, Invivo) with standard 12-core TRUS biopsy in same procedure from 7/2014-10/2014. Patients first had multiparametric prostate MRI (3T without endorectal coil) and target lesions of interest (LOI) for biopsy were marked. Median number of LOI/ patient was 2. Median number of cores per LOI was 3. These patients were compared to a cohort of 55 patients from 2011-2013 undergoing saturation ( 20 cores) TRUS biopsy as part of an active surveillance protocol. RESULTS: Overall, there was no difference between groups in cancer detection or reclassification (p>0.05). Results summarized in table below. The mean total number of cores was higher with saturation biopsy vs. MR-US-FB (20 1.5 vs. 18 5.4, p

INTRODUCTION AND OBJECTIVES: Following radical cystectomy (RC) for urothelial carcinoma (UC) of the bladder cancer, a proportion of clinically node negative patients will be diagnosed with metastasis in the regional lymph nodes (pNþ). A number of clinical factors such as local stage and lymphovascular invasion (LVI) have been identified as potential predictors for pNþ status; however, these have not been assessed in patients treated with neoadjuvant chemotherapy (NAC). Our objective is to assess clinical and therapeutic factors predicting pNþ in clinically node negative patients treated with NAC and RC. METHODS: Patients from four North American institutions with cT2-4N0M0 UC who received three or four cycles of NAC followed by RC were included. A logistic regression model was formulated for predicting pNþ status. The variables included were age, gender, clinical T-stage, transurethral resection (TUR) histology (UC or UC variant) and LVI, number of cycles of NAC, the regimen administered and the extent of pelvic node dissection. RESULTS: The analysis was conducted on 238 patients. Median age was 64 years (IQR: 58-71) and 79% of patients were male. The clinical stage was cT2 in 143 (60.1%), cT3 in 76 (39.1%) and cT4 in 19 (8%) cases. MVAC was used in 26.9% and GC in the remainder of the patients. 60.9% of the MVAC group received four cycles of NAC compared to 42.5% of the GC group (p1⁄40.013). Pathological Nþ was seen in 45 (19.5%) patients. In the logistic regression analysis, cT4 stage (OR: 3.32, [95% CI: 1.15-9.56]) and the fewer cycles of NAC (3 vs. 4 cycles OR: 2.10, [95% CI: 1.03-4.29]) were significant predictors of pNþ status. LVI was not significant in this cohort of patients (OR: 1.15, [95%CI 0.50-2.63]). The observed advantage of the additional cycle of NAC was persistent in subanalysis of the GC patients (OR: 2.67, [CI: 1.11-6.41]) but not MVAC patients (OR: 1.11, [CI: 0.25-4.92]). CONCLUSIONS: Patients with locally advanced disease are at higher risk of harboring lymph node metastasis at the time of RC following NAC. LVI in the TUR specimen was not a significant predictor of nodal metastasis in these patients. Potential advantage of an additional cycle of NAC in GC patients requires further confirmation.

We endeavored to summarize the most relevant data in regards of oncologic patient outcome prediction in the transitional cell carcinoma (TCC) topic. Nomograms have been used to standardize this outcome and more accurately predict future events. Bladder cancer still remains a very poor field compared to other areas such as prostate or kidney cancer. In order to facilitate understanding, we organized the chapter by tumor depth of invasion meaning, noninvasive versus invasive bladder cancer. We included a short paragraph about upper tract TCC nomograms. None of the presented nomograms is currently used on a daily basis for patient clinical care due to the lack of external validity in most environments.

Nomograms facilitate the conversation between the physician and the patient when discussing all the potential treatment options for localized prostate cancer. By using continuous, multivariable models—nomograms—the patient has an accurate means to determine estimation of success and make decisions on therapy that are most in line with his beliefs and fit his lifestyle. Currently, there are multiple nomograms that address all the different variables present at each of the clinical states of prostate cancer. As therapies evolve and series mature, these prediction models need to be updated and revalidated to best predict the likelihood of long-term urinary and sexual function, as well as oncological outcomes.

Patients with metastatic testicular cancer with residual masses encasing the renal hilum or kidney after platin based chemotherapy may require adjunctive nephrectomy to achieve complete resection at post-chemotherapy retroperitoneal lymph node dissection. We reviewed our experience with adjunctive nephrectomy to assess the impact on cancer control and renal function.Of 647 post-chemotherapy retroperitoneal lymph node dissection procedures performed at our institution since 1989 adjunctive nephrectomy has been performed in 32 patients (5%). Patient information was obtained from a prospective database. Median followup was 31 months.Of the adjunctive nephrectomy procedures 17 (53%) were performed in high risk settings such as post-salvage chemotherapy, desperation retroperitoneal lymph node dissection, late relapse and reoperative retroperitoneal lymph node dissection. Disease was present in the adjunctive nephrectomy specimen in 21 patients (66%). Following post-chemotherapy retroperitoneal lymph node dissection 7 patients had disease relapse and 5-year disease-free survival was 66%. No case of relapse required substitution for cisplatin due to compromised renal function. Progression to chronic renal insufficiency occurred in 3 patients, 1 of whom required hemodialysis. The calculated creatinine clearance after adjunctive nephrectomy was more than 30% below the age specific norm in 14 patients (50%) and median patient age was 40 years.Adjunctive nephrectomy at post-chemotherapy retroperitoneal lymph node dissection is most frequently performed in patients with high risk features to ensure the completeness of resection. When indicated, adjunctive nephrectomy should be performed because residual cancer is frequently present and long-term cancer control can be achieved in 66% of patients. Although adjunctive nephrectomy did not interfere with subsequent chemotherapy, the renal reserve in these patients was substantially reduced in 50%, emphasizing the importance of preventative measures to preserve long-term renal function.

Accurate estimates of risk are essential for physicians if they are to recommend a specific management to patients with prostate cancer. In addition their incorporation into clinical trial design ensures homogeneous high-risk patient groups for whom new cancer therapeutics are to be investigated. Using MEDLINE we performed a literature search on articles on prostate cancer predictive tools published during the period from January 1966 to July 2007. We recorded input variables, prediction form, number of patients used to develop the prediction tool, the outcome being predicted, prediction tool-specific features, predictive accuracy, and whether validation was performed. The literature search generated 109 published prediction tools from which only 68 had undergone validation. In this chapter we describe the criteria for evaluation (predictive accuracy, calibration, generalizability, head-to-head comparison, and level of complexity) and limitations of current predictive tools. Our review indicates that an increasing number of predictive tools addresses important endpoints such as disease recurrence, metastasis, and survival. For choosing among prediction tools, our recommendation is nomograms, which provide superior individualized risk estimation. Nevertheless, many more predictive tools, comparisons between them, and improvements to existing tools are needed.

Purpose A postoperative nomogram for prostate cancer recurrence after radical prostatectomy (RP) has been independently validated as accurate and discriminating. We have updated the nomogram by extending the predictions to 10 years after RP and have enabled the nomogram predictions to be adjusted for the disease-free interval that a patient has maintained after RP. Methods Cox regression analysis was used to model the clinical information for 1,881 patients who underwent RP for clinically-localized prostate cancer by two high-volume surgeons. The model was externally validated separately on two independent cohorts of 1,782 patients and 1,357 patients, respectively. Disease progression was defined as a rising prostate-specific antigen (PSA) level, clinical progression, radiotherapy more than 12 months postoperatively, or initiation of systemic therapy. Results The 10-year progression-free probability for the modeling set was 79% (95% CI, 75% to 82%). Significant variables in the multivariable model included PSA (P = .002), primary (P < .0001) and secondary Gleason grade (P = .0006), extracapsular extension (P < .0001), positive surgical margins (P = .028), seminal vesicle invasion (P < .0001), lymph node involvement (P = .030), treatment year (P = .008), and adjuvant radiotherapy (P = .046). The concordance index of the nomogram when applied to the independent validation sets was 0.81 and 0.79. Conclusion We have developed and validated as a robust predictive model an enhanced postoperative nomogram for prostate cancer recurrence after RP. Unique to predictive models, the nomogram predictions can be adjusted for the disease-free interval that a patient has achieved after RP.

Objectives To analyze the feasibility of neurovascular bundle (NVB) preservation and peripheral nerve grafting during salvage radical prostatectomy (RP) for radiorecurrent prostate cancer and analyze their effect on the recovery of potency. Methods Of 100 patients who underwent salvage RP with curative intent from 1984 to 2003, 7 patients had bilateral NVBs preserved, 22 had a unilateral NVB preserved with (n = 11) and without (n = 11) a unilateral nerve graft, and 9 had bilateral NVBs resected with bilateral nerve grafts. Preoperative erections were graded as normal (grade 1) in 12 patients and full but recently diminished (grade 2) in 16. Recovery of potency after salvage RP was defined as erections satisfactory for intercourse, with or without the use of sildenafil. Results Overall, 6 patients recovered potency after salvage RP, and the 5-year actuarial recovery rate was 16% (95% confidence interval 4% to 28%). The 6 patients who recovered erections all had preoperative grade 1 to 2 erections, and 5 had bilateral NVBs preserved. Only 1 of 11 patients who had a unilateral nerve graft recovered potency. No patient with bilateral nerve grafts recovered potency. The 5-year actuarial recovery rate among patients with preoperative grade 1 to 2 erections was 45% (95% confidence interval 16% to 75%). Conclusions Compared with standard RP, the overall potency results after salvage RP are poor. However, select patients with good preoperative erectile function who have bilateral NVB preservation may recover erections sufficient for intercourse aided by sildenafil. Peripheral nerve grafts did not appear to influence the recovery of erections in this patient population.