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Background: Most safety and efficacy trials of the SARS-CoV-2 vaccines excluded patients with cancer, yet these patients are more likely than healthy individuals to contract SARS-CoV-2 and more likely to become seriously ill after infection. Our objective was to record short-term adverse reactions to the COVID-19 vaccine in patients with cancer, to compare the magnitude and duration of these reactions with those of patients without cancer, and to determine whether adverse reactions are related to active cancer therapy. Patients and Methods: A prospective, single-institution observational study was performed at an NCI-designated Comprehensive Cancer Center. All study participants received 2 doses of the Pfizer BNT162b2 vaccine separated by approximately 3 weeks. A report of adverse reactions to dose 1 of the vaccine was completed upon return to the clinic for dose 2. Participants completed an identical survey either online or by telephone 2 weeks after the second vaccine dose. Results: The cohort of 1,753 patients included 67.5% who had a history of cancer and 12.0% who were receiving active cancer treatment. Local pain at the injection site was the most frequently reported symptom for all respondents and did not distinguish patients with cancer from those without cancer after either dose 1 (39.3% vs 43.9%; P=.07) or dose 2 (42.5% vs 40.3%; P=.45). Among patients with cancer, those receiving active treatment were less likely to report pain at the injection site after dose 1 compared with those not receiving active treatment (30.0% vs 41.4%; P=.002). The onset and duration of adverse events was otherwise unrelated to active cancer treatment. Conclusions: When patients with cancer were compared with those without cancer, few differences in reported adverse events were noted. Active cancer treatment had little impact on adverse event profiles.

Purpose:Rocapuldencel-T is an autologous immunotherapy prepared from mature monocyte-derived dendritic cells (DC), coelectroporated with amplified tumor RNA plus CD40L RNA. This pivotal phase III trial was initiated to investigate the safety and efficacy of a combination therapy dosing regimen of Rocapuldencel-T plus sunitinib in patients with metastatic renal cell carcinoma (mRCC).Patients and Methods:Patients received either Rocapuldencel-T plus standard of care (SOC) or SOC treatment alone. The primary objective compared overall survival (OS) between groups. Secondary objectives included safety assessments, progression-free survival (PFS), and tumor responses based on RECIST 1.1 criteria. Exploratory analyses included immunologic assessments and correlates with OS.Results:Between 2013 and 2016, 462 patients were randomized 2:1, 307 to the combination group and 155 to the SOC group. Median OS in the combination group was 27.7 months [95% confidence interval (CI) 23.0–35.9] and 32.4 months (95% CI, 22.5–) in the SOC group HR of 1.10 (95% CI, 0.83–1.40). PFS was 6.0 months and 7.83 months for the combination and SOC groups, respectively [HR = 1.15 (95% CI, 0.92–1.44)]. The ORR was 42.7% (95% CI, 37.1–48.4) for the combination group and 39.4% (95% CI, 31.6–47.5) for the SOC group. Median follow up was 29 months (0.4–47.7 months). On the basis of the lack of clinical efficacy, the ADAPT trial was terminated on February 17, 2017. Immune responses were detected in 70% of patients treated with Rocapuldencel-T, and the magnitude of the immune response positively correlated with OS. In addition, we report the survival-predictive value of measuring IL-12 produced by the DC vaccine and the observation that high baseline numbers of T regulatory cells are associated with improved outcomes in DC-treated patients, but are associated with poor outcomes in patients receiving SOC treatment. No serious adverse events attributed to the study medication have been reported to date.Conclusions:Rocapuldencel-T did not improve OS in patients treated with combination therapy, although the induced immune response correlated with OS. Moreover, we identified two potential survival-predictive biomarkers for patients receiving DC based immunotherapy, IL-12 produced by the DC vaccine and higher numbers of T regulatory cells present in the peripheral blood of patients with advanced RCC.

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Background: Men with familial prostate cancer and African American men are at risk for developing prostate cancer at younger ages. Genetic markers predicting early-onset prostate cancer may provide clinically useful information to guide screening strategies for high-risk men. We evaluated clinical information from six polymorphisms associated with early-onset prostate cancer in a longitudinal cohort of high-risk men enrolled in prostate cancer early detection with significant African American participation.Methods: Eligibility criteria include ages 35 to 69 with a family history of prostate cancer or African American race. Participants undergo screening and biopsy per study criteria. Six markers associated with early-onset prostate cancer [rs2171492 (7q32), rs6983561 (8q24), rs10993994 (10q11), rs4430796 (17q12), rs1799950 (17q21), and rs266849 (19q13)] were genotyped. Cox models were used to evaluate time to prostate cancer diagnosis and prostate-specific antigen (PSA) prediction for prostate cancer by genotype. Harrell's concordance index was used to evaluate predictive accuracy for prostate cancer by PSA and genetic markers.Results: Four hundred and sixty participants with complete data and ≥1 follow-up visit were included. Fifty-six percent were African American. Among African American men, rs6983561 genotype was significantly associated with earlier time to prostate cancer diagnosis (P = 0.005) and influenced prediction for prostate cancer by the PSA (P < 0.001). When combined with PSA, rs6983561 improved predictive accuracy for prostate cancer compared with PSA alone among African American men (PSA = 0.57 vs. PSA + rs6983561 = 0.75, P = 0.03).Conclusions: Early-onset marker rs6983561 adds potentially useful clinical information for African American men undergoing prostate cancer risk assessment. Further study is warranted to validate these findings.Impact: Genetic markers of early-onset prostate cancer have potential to refine and personalize prostate cancer early detection for high-risk men. Cancer Epidemiol Biomarkers Prev; 21(1); 53–60. ©2011 AACR.

ADAPT study group and participating centers

OBJECTIVES To determine whether patients with carcinoma invading bladder muscle (MIBC) and ureteric obstruction can safely receive cisplatin-based neoadjuvant chemotherapy (C-NAC), and to determine whether such patients require relief of obstruction with a ureteric stent or percutaneous nephrostomy prior to beginning C-NAC. PATIENTS AND METHODS We performed a single-institution retrospective analysis of MIBC patients receiving C-NAC and falling into three groups: no ureteric obstruction (NO); relieved ureteric obstruction (RO); and unrelieved ureteric obstruction (URO). To address whether patients with obstruction can safely receive C-NAC, we compared patients with NO to those with RO, with the primary outcome of premature chemotherapy discontinuation. To investigate whether patients with obstruction should have the obstruction relieved prior to NAC, we compared RO to URO patients using a primary composite outcome of grade ≥ 3 adverse events, premature chemotherapy discontinuation, dose reduction, or dose interruption. The primary outcomes were compared using multivariable logistic regression. Sensitivity analyses were performed for the RO vs URO comparison, in which patients with only mild degrees of obstruction were excluded from the URO group. RESULTS A total of 193 patients with NO, 49 with RO, and 35 with URO were analysed. There were no statistically significant differences between those with NO and those with RO in chemotherapy discontinuation (15% vs 22%; P = 0.3) or any secondary outcome. There was no statistically significant difference between those with RO and URO in the primary composite outcome (51% vs 53%; P = 1) or any secondary outcome. CONCLUSION Patients with ureteric obstruction can safely receive C-NAC. Relief of obstruction was not associated with increased safety of C-NAC delivery.

Early-onset renal cell carcinoma (eoRCC) is typically associated with pathogenic germline variants (PGVs) in RCC familial syndrome genes. However, most eoRCC patients lack PGVs in familial RCC genes and their genetic risk remains undefined. Here, we analyzed biospecimens from 22 eoRCC patients that were seen at our institution for genetic counseling and tested negative for PGVs in RCC familial syndrome genes. We performed whole-exome sequencing (WES) and found enrichment of candidate pathogenic germline variants in DNA repair and replication genes, including multiple DNA polymerases. Induction of DNA damage in peripheral blood monocytes (PBMCs) significantly elevated numbers of γH2AX foci, a marker of double-stranded breaks, in PBMCs from eoRCC patients versus PBMCs from matched cancer-free controls. Knockdown of candidate PGVs in Caki RCC cells increased γH2AX foci. Immortalized patient-derived B cells bearing candidate PGVs in DNA polymerase genes (POLD1, POLH, POLE, POLK) had DNA replication defects compared to control cells. Renal tumors carrying these DNA polymerase variants were microsatellite stable but had a high mutational burden. Direct biochemical analysis of the variant Pol δ and Pol η polymerases revealed defective enzymatic activities. Together, these results suggest that constitutional defects in DNA repair such as DNA replication repair underlie a subset of eoRCC cases. These findings may provide opportunities for use of the DNA repair targeting agents for eoRCC treatment. Screening patient lymphocytes to identify these defects may provide insight into mechanisms of carcinogenesis in a subset of genetically undefined eoRCCs.Significance StatementScreening for DNA repair variation may provide a more comprehensive risk assessment for eoRCC patients. Evaluation of DNA repair defects may also provide insight into the cancer initiation mechanisms for subsets of eoRCCs and lay the foundation for targeting DNA repair vulnerabilities in eoRCC.

Introduction:Following transurethral resection of bladder tumor, patients can be discharged home, observed for 24 hours or admitted to the hospital. While disposition can impact care delive...

To investigate the association of surgical approach with outcomes in patients with adrenocortical carcinomas smaller and larger than 6 cm in size.We reviewed the national cancer database for patients undergoing minimally invasive adrenalectomy (MIA) and open adrenalectomy (OA) from 2010 to 2017. To adjust for differences between patients undergoing MIA and OA, we performed propensity score matching within each size strata of ≤6 cm, 6.1 to 10 cm, and 10.1 to 20 cm. We fit generalized estmiating equations with a logit link function to assess for the association of surgical approach with positive surgical margins and a Cox proportional hazards model to assess for the association of surgical approach with overall survival.We identified 364 patients that underwent MIA (182) and OA (182) in the matched cohort. We noted 21% and 18% of patients undergoing MIA and OA had a positive surgical margin, respectively. We did not identify a significant association between surgical approach and positive surgical margins in the cohort as a whole or within each of strata. Furthermore, we did not appreciate a significant association between surgical approach and overall survival in the cohort as a whole or within each size strata.In the National Cancer Database, patients undergoing MIA had similar positive surgical margins and overall survival compared with OA for masses ≤6 cm, 6.1 to 10cm, and10 cm in size. Patients undergoing MIA should be carefully selected with surgical oncologic integrity being the primary determinants of surgical approach.

In the National Cancer Database (NCDB), patients treated with minimally invasive adrenalectomy (MIA) for adrenocortical carcinoma (ACC) had similar oncological outcomes and cumulative treatment burden with less morbidity compared with open adrenalectomy (OA). Although OA remains the standard of care for adrenal lesions concerninge for malignancy, MIA in appropriately selected patients may offer equivalent oncological outcomes.We investigated the cumulative treatment burden, oncological effectiveness, and perioperative morbidity in patients undergoing MIA compared with (OA) for patients with ACC.We reviewed the NCDB for patients undergoing surgical resection (MIA vs. OA) for ACC from 2010 to 2017. Inverse probability of treatment weighted logistic regression, negative binomial, and Cox proportional hazards models were fit to assess for an association of surgical approach with cumulative treatment burden (any adjuvant therapy, radiation therapy [RT], and systemic therapy), oncological effectiveness (positive surgical margins [PSM], lymph node yield [LNY], and overall survival [OS]), and perioperative morbidity (length of stay [LOS] and readmission) as appropriate.We identified 776 patients that underwent adrenalectomy for ACC, of which 307 underwent MIA. We noted patients with larger tumors (OR 0.82, 95% CI 0.78-0.86, P.001) were less likely to have MIA prior to IPTW. We did not appreciate a significant association of MIA with cumulative treatment burden or the use of any adjuvant therapy (OR 0.85, 95% CI 0.60-1.21, P = .375), adjuvant RT (OR 0.94, 95% CI 0.59-1.50, P = .801), or adjuvant systemic therapy (OR 0.84, 95% CI 0.58-1.21, P = .352). Patients undergoing MIA had similar oncological effectiveness of surgery and OS when compared with patients which underwent OA. Patients that underwent MIA had a significantly shorter LOS (IRR: 0.74, 95% CI 0.62-0.88, P = .001) and lower odds of readmission (OR 0.46, 95% CI 0.23-0.91, P = .026).Although the standard of care for adrenal lesions suspicious for ACC remains OA, in appropriately selected patients, MIA may offer similar oncological effectiveness and cumulative treatment burden, with less morbidity, than OA.

Introduction:Bacillus Calmette-Guerin production is limited worldwide with stuttering shortages affecting patient access. Our institution received 50 vials of bacillus Calmette-Guerin label...

Objectives To develop a clinically applicable predictive model to quantitate the risk of estimated glomerular filtration rate (eGFR) decline to ≤45 mL/min/1.73 m2 after radical nephrectomy (RN) to better inform decisions between RN and partial nephrectomy (PN). Patients and methods Our prospectively maintained kidney cancer registry was reviewed for patients with a preoperative eGFR >60 mL/min/1.73 m2 who underwent RN for a localized renal mass. New baseline renal function was indexed. We used multivariable logistic regression to develop a predictive nomogram and evaluated it using receiver-operating characteristic (ROC) analysis. Decision-curve analysis was used to assess the net clinical benefit. Results A total of 668 patients met the inclusion criteria, of whom 183 (27%) experienced a decline in eGFR to ≤45 mL/min/1.73 m2 . On multivariable analysis, increasing age (P = 0.001), female gender (P ~11%. Conclusions The decision to perform RN vs PN is multifaceted. We have provided a simple quantitative tool to help identify patients at risk of a postoperative eGFR of ≤45 mL/min/1.73 m2 , who may be stronger candidates for nephron preservation.

Objective To perform a comprehensive histopathologic review of sporadic resected solitary cT1 renal masses comparing those with and without radiographic involvement of the hilum. Materials and Methods A prospectively maintained database was queried for all cT1 renal masses undergoing resection classified per the R.E.N.A.L. nephrometry score. Hilar masses were defined as tumors that abut the main renal artery or vein on cross-sectional imaging. Demographic, treatment, renal mass, and histopathologic characteristics were compared between hilar and nonhilar renal masses. Multivariate regression model analyses were performed to assess factors associated with renal mass upstaging and disease recurrence. Results A total of 1324 stage 1 renal masses met criteria for analysis of which 226 (17.1%) were defined as hilar. Hilar masses were larger, scored with higher complexity, and more likely to undergo a radical nephrectomy. On histopathologic analysis, we found no difference between hilar and nonhilar masses regarding the incidence of malignancy, presence of high nuclear grade, or risk of upstaging. On multivariate analysis, a tumor's hilar location was not associated with upstaging or disease recurrence. Conclusion We present a comprehensive histopathologic review of a large cohort of cT1 hilar lesions noting no difference in the risk of malignancy, high nuclear grade, upstaging, or recurrence when compared to nonhilar lesions. Together, these data suggest that there is no compelling cancer-specific rationale to perform a radical nephrectomy when managing renal hilar tumors.

Purpose Multigene panels are commercially available for the evaluation of prostate cancer (PCA) predisposition, which necessitates tailored genetic counseling (GC) for men. Here we describe emerging results of Genetic Evaluation of Men, prospective multigene testing study in PCA to inform personalized genetic counseling, with emerging implications for referrals, cancer screening, and precision therapy. Patients and Methods Eligibility criteria for men affected by or at high risk for PCA encompass age, race, family history (FH), and PCA stage/grade. Detailed demographic, clinical, and FH data were obtained from participants and medical records. Multigene testing was conducted after GC. Mutation rates were summarized by eligibility criteria and compared across FH data. The 95% CI of mutation prevalence was constructed by using Poisson distribution. Results Of 200 men enrolled, 62.5% had PCA. Eleven (5.5%; 95% CI, 3.0% to 9.9%) had mutations; 63.6% of mutations were in DNA repair genes. FH of breast cancer was significantly associated with mutation status ( P = .004), and FH that met criteria for hereditary breast and ovarian cancer syndrome was significantly associated with PCA (odds ratio, 2.33; 95% CI, 1.05 to 5.18). Variants of uncertain significance were reported in 70 men (35.0%). Among mutation carriers, 45.5% had personal/FH concordant with the gene. A tailored GC model was developed based on emerging findings. Conclusion Multigene testing for PCA identifies mutations mostly in DNA repair genes, with implications for precision therapy. The study highlights the importance of comprehensive genetic evaluation for PCA beyond metastatic disease, including early-stage disease with strong FH. Detailed FH is important for referrals of men for genetic evaluation. The results inform precision GC and cancer screening for men and their male and female blood relatives.

INTRODUCTION: Distinct PSA kinetics have been reported across the breadth of radiation modalities used to definitively treat prostate cancer. This study uses a patient-specific model to characterize and compare ideal PSA kinetics for low- and intermediate-risk prostate cancer following definitive treatment with conventionally fractionated (CFRT), hypofractionated (HFRT), ultra-hypofractionated or stereotactic body radiation therapy (SbRT), or brachytherapy, both high-dose-rate (HDR) and low-dose-rate (LDR). METHODS: This retrospective analysis includes patients with low- or intermediate-risk prostate cancer treated with definitive radiation between 1998 and 2018 at a single, NCI-designated Comprehensive Cancer Center. Patient demographics, treatment characteristics, and follow-up information were prospectively collected in an institutional database. Eligible patients had at least two PSA measurements within 24-months of treatment and were free from biochemical recurrence and receipt of androgen deprivation therapy. The incidence of, time to, and risk factors for PSA nadir (nPSA) and bounce (bPSA) were analyzed by radiation modality. Ideal PSA kinetics were characterized for each modality and compared. RESULTS: Of 1,047 patients included, 45% had low-risk prostate cancer, 37% had favorable intermediate-risk, and 19% had unfavorable intermediate-risk. The majority of patients were treated with CFRT or LDR; the smallest subset was 52 patients (5%) who received SbRT. nPSA measurements within the two-year follow-up period were significantly higher for those treated with ablative modalities, both as absolute nPSA values and relative to initial PSA (iPSA). Median time to nPSA ranged from 14.8 to 17.1 months. Over 50% of those treated with non-ablative therapy (CFRT, HFRT, and LDR) reached a critical nPSA threshold of ≤0.5 ng/mL, while only 23% of SbRT and 33% of HDR cohorts achieved the same threshold. The overall incidence of bPSA was 13.3% and was not affected by treatment modality, Gleason Score, or prostate volume. A piecewise linear regression showed no statistically significant difference in the PSA decay rates between radiation modalities over time, though there was a trend toward faster PSA decay in ablative therapies between the 6–24-month period. CONCLUSION: Ablative therapies, such as HDR and SbRT, are associated with a latent PSA response and higher nPSA when compared to non-ablative therapies. Multivariate logistics modeling revealed younger age, iPSA above the mean, presence of bPSA, and receipt of ablative therapy as significant predictors for not achieving an nPSA ≤0.5 ng/mL. Understanding the different PSA kinetic profiles for the various radiation modalities is critical to assess treatment response and survey for disease recurrence.

Purpose We sought to compare changes in patient-reported quality of life (PRQOL) following stereotactic body radiation therapy (SBRT), high dose rate (HDR), and low dose rate (LDR) brachytherapy for prostate cancer. Materials and methods International Prostate Symptom Score (IPSS), Sexual Health Inventory For Men (SHIM), and Expanded Prostate cancer Index Composite Short Form (EPIC-26) were prospectively collected for men with low/intermediate-risk cancer treated at a single institution. We used Generalized Estimating Equations to identify associations between variables and early (3 to 6 mo) or late (1 to 2 y) PRQOL scores. Minimally important differences (MID) were compared with assess clinical relevance. Results A total of 342 LDR, 159 HDR, and 112 SBRT patients treated from 2001 to 2018 were eligible. Gleason score, PSA, and age were lower among LDR patients compared with HDR/SBRT. Unadjusted baseline IPSS score was similar among all groups. Adjusted IPSS worsened at all time points compared with baseline after LDR/HDR. At early/late time points, rates of IPSS MID after LDR were higher compared to HDR/SBRT. There were no IPSS differences between SBRT and HDR. All modalities showed early and late SHIM worsening. There were no temporal differences in SHIM between SBRT and brachytherapy. There were no differences in EPIC subdomains between HDR and SBRT. Bowel symptoms worsened early after SBRT, whereas urinary irritative/obstructive symptoms worsened late after HDR. Among all domains, MID after SBRT and HDR were similar. Conclusions In a cohort of patients treated with modern radiotherapy techniques, HDR and SBRT resulted in clinically meaningful improved urinary PRQOL compared with LDR.

Concern for discordance between clinical staging and final pathology drives current management of patients deemed appropriate candidates for radical cystectomy. Therefore, we set out to prospectively investigate reliability and shortcomings of cystoscopic evaluation in radical cystectomy candidates.Patients undergoing radical cystectomy for urothelial carcinoma were enrolled in a prospective single-arm study to evaluate reliability of Systematic Endoscopic Evaluation in predicting pT0 urothelial carcinoma (NCT02968732). Systematic Endoscopic Evaluation consisted of cystoscopy and tissue sampling at the time of radical cystectomy. Systematic Endoscopic Evaluation results were compared to radical cystectomy pathology. The primary end point was the negative predictive value of Systematic Endoscopic Evaluation findings in predicting radical cystectomy pathology.A total of 61 patients underwent Systematic Endoscopic Evaluation and radical cystectomy. Indications included muscle invasive bladder cancer in 42 (68.9%) and high risk nonmuscle invasive bladder cancer in 19 (31.1%). In all, 38 (62.3%, 90.5% of patients with muscle invasive bladder cancer) received neoadjuvant chemotherapy. On Systematic Endoscopic Evaluation, 31 (50.8%) patients demonstrated no visual nor biopsy-based evidence of disease (seeT0), yet 16/31 (51.6%) harbored residual disease (pT0), including 8 (8/31, 25.8%) with residual ≥pT2 disease upon radical cystectomy. The negative predictive value of Systematic Endoscopic Evaluation predicting a pT0 bladder was 48.4% (CI 30.2-66.9), which was below our prespecified hypothesis. Therefore, the trial was stopped for futility.Approximately 1 of 4 patients with seeT0 at the time of radical cystectomy harbored residual muscle invasive bladder cancer. These prospective data definitively confirm major limitations of endoscopic assessment for pT0 bladder cancer. Future work should focus on novel imaging and biomarker strategies to optimize evaluations before radical cystectomy for improved decision making regarding bladder preservation.

AIMS As COVID-19 continues to spread globally, the urgency for effective diagnostic testing escalates. Medical imaging has revolutionized healthcare as a critical step to early diagnosis, leading to immediate isolation and optimized treatment pathways. Current imaging modalities such as the lung ultrasound, chest X-ray, and computed tomography (CT) scan are critical in COVID-19 detection. However, overlap in clinical characteristics with other viral respiratory illnesses poses a significant risk for misdiagnosis. METHODOLOGY To address the need for information concerning the effectiveness of Coronavirus disease 2019 (COVID-19) diagnostic procedures, this paper reviews different imaging modalities, evaluating various factors including sensitivity, specificity, cost, diagnosis time, accessibility, safety, ease of implementation, and potential for optimization. The literature search reviewed databases including PubMed, Google Scholar, Sonography Canada, Cochrane Review, and Novanet using keywords to filter results. A utilitarian approach was employed to further refine selection criteria and to assess credibility and relevance. Applicable data was then extracted from literature for analysis considering the relationships between studies. RESULTS AND CONCLUSIONS The imaging modalities reviewed in this paper each have unique advantages. The lung ultrasound, with moderate sensitivity, permits regular monitoring due to its accessibility. Chest X-rays are effective at processing detailed images of the lungs to detect abnormalities but are not confirmed as a precise method for diagnosis. While CT scans show morphological features of COVID-19 with superior sensitivity, it is incapable of accurately differentiating coronavirus from other pulmonary diseases. Overall, a multimodality approach would be most effective for COVID-19 diagnosis and monitoring, preventing over dependence on CT scans.

PURPOSE Germline testing (GT) is a central feature of prostate cancer (PCA) treatment, management, and hereditary cancer assessment. Critical needs include optimized multigene testing strategies that incorporate evolving genetic data, consistency in GT indications and management, and alternate genetic evaluation models that address the rising demand for genetic services. METHODS A multidisciplinary consensus conference that included experts, stakeholders, and national organization leaders was convened in response to current practice challenges and to develop a genetic implementation framework. Evidence review informed questions using the modified Delphi model. The final framework included criteria with strong (> 75%) agreement (Recommend) or moderate (50% to 74%) agreement (Consider). RESULTS Large germline panels and somatic testing were recommended for metastatic PCA. Reflex testing—initial testing of priority genes followed by expanded testing—was suggested for multiple scenarios. Metastatic disease or family history suggestive of hereditary PCA was recommended for GT. Additional family history and pathologic criteria garnered moderate consensus. Priority genes to test for metastatic disease treatment included BRCA2, BRCA1, and mismatch repair genes, with broader testing, such as ATM, for clinical trial eligibility. BRCA2 was recommended for active surveillance discussions. Screening starting at age 40 years or 10 years before the youngest PCA diagnosis in a family was recommended for BRCA2 carriers, with consideration in HOXB13, BRCA1, ATM, and mismatch repair carriers. Collaborative (point-of-care) evaluation models between health care and genetic providers was endorsed to address the genetic counseling shortage. The genetic evaluation framework included optimal pretest informed consent, post-test discussion, cascade testing, and technology-based approaches. CONCLUSION This multidisciplinary, consensus-driven PCA genetic implementation framework provides novel guidance to clinicians and patients tailored to the precision era. Multiple research, education, and policy needs remain of importance.

INTRODUCTION AND OBJECTIVE:Renal mass biopsy (RMB) has not been adopted widely by urologists for the evaluation of small renal mass (SRM) before considering surgical intervention due to concerns fo...

PURPOSE The previously published single institution randomized prospective trial failed to show superiority in the 5-year biochemical and/or clinical disease failure (BCDF) rate with moderate hypofractionated intensity-modulated radiation therapy (H-IMRT) versus conventionally fractionated IMRT (C-IMRT). We now present 10-year disease outcomes using updated risk groups and definitions of biochemical failure. METHODS Men with protocol-defined intermediate- and high-risk prostate adenocarcinoma were randomly assigned to receive C-IMRT (76 Gy in 38 fractions) or H-IMRT (70.2 Gy in 26 fractions). Men with high-risk disease were all prescribed 24 months of androgen deprivation therapy (ADT) and had lymph node irradiation. Men with intermediate risk were prescribed 4 months of ADT at the discretion of the treating physician. The primary endpoint was cumulative incidence of BCDF. We compared disease outcomes and overall mortality by treatment arm, with sensitivity analyses for National Comprehensive Cancer Network (NCCN) risk group adjustment. RESULTS Overall, 303 assessable men were randomly assigned to C-IMRT or H-IMRT. The median follow-up was 122.9 months. Per updated NCCN risk classification, there were 28 patients (9.2%) with low-risk, 189 (62.4%) with intermediate-risk, and 86 (28.4%) with high-risk prostate cancer. The arms were equally balanced for clinicopathologic factors, except that there were more black patients in the C-IMRT arm (17.8% v 7.3%; P = .02). There was no difference in ADT use ( P = .56). The 10-year cumulative incidence of BCDF was 25.9% in the C-IMRT arm and was 30.6% in the H-IMRT arm (hazard ratio, 1.31; 95% CI, 0.82 to 2.11). The two arms also had similar cumulative 10-year rates of biochemical failure, prostate cancer–specific mortality, and overall mortality; however, the 10-year cumulative incidence of distant metastases was higher in the H-IMRT arm (rate difference, 7.8%; 95% CI, 0.7% to 15.1%). CONCLUSION H-IMRT failed to demonstrate superiority compared with C-IMRT in long-term disease outcomes.

Cisplatin-based neoadjuvant chemotherapy (NAC) has demonstrated an overall survival (OS) benefit in muscle invasive bladder cancer (MIBC). However, only a subset of patients (25–50%) have pathologic complete response at cystectomy. Using a cohort of patients (n = 58) from two phase II trials, our group previously reported that mutations in the ATM, RB1, and FANCC genes correlate with complete response to cisplatin-based NAC, and consequently improved overall and disease specific survival. These trials enrolled patients with T2-T4 (N0 or N1) MIBC and treated them with dose dense NAC with MVAC (methotrexate, vinblastine, adriamycin, and cisplatin) or Gem/Cis (gemcitabine and cisplatin) with plan for curative cystectomy. Updated long-term follow up (median follow-up = 74 months) shows that patients with mutations in ATM, RB1 or FANCC maintained significantly greater OS and DSS. The 5-year-survival rate for patients with at least one mutation was 85% compared to 45% for patients without a mutation. Based on the association with response, long-term OS and DSS, we propose that these alterations may be useful as predictive biomarkers to allow clinicians to prioritize patients who are most likely to benefit from NAC prior to radical cystectomy. PATIENT SUMMARY: (2–3 short sentences in plain English to describe your findings to a non-medical audience. For example: “In this report we looked at the outcomes from invasive bladder cancer in a large European population. We found that outcomes varied with patient age and treating centre. We conclude that the best outcomes are seen in younger patients treated at high volume hospitals.”): In this report we looked at the outcomes for patients with muscle-invasive bladder cancer treated with cisplatin-based chemotherapy before surgery (neoadjuvant) who had mutations in a set of DNA damage repair genes (ATM, RB1, FANCC) compared to those who did not. We found that patients who had at least one mutation in one of these genes survived longer after receiving cisplatin chemotherapy before surgery than patients who did not.

Inguinal lymphadenectomy remains under performed in patients with invasive penile cancer. Using a large national cancer registry we assessed temporal trends in inguinal lymphadenectomy performance and evaluated the impact of the procedure on survival in patients in whom inguinal lymphadenectomy was an absolute indication (T1b-4 N0/x-1) according to NCCNWe queried the National Cancer Database for all cases of nonmetastatic, T1b-4 N0/x-1 squamous cell carcinoma of the penis from 2004 to 2014. Multivariable logistic regression models adjusting for patient, demographic, and clinicopathological characteristics were used to examine the association between available covariates and receipt of inguinal lymphadenectomy. Cox proportional hazards regression analysis was then done to assess the impact of clinical and pathological variables on overall survival. Propensity score weighted analysis was performed to assess the effect of inguinal lymphadenectomy on overall survival.A total of 2,224 patients met analysis criteria, of whom 606 (27.2%) underwent inguinal lymphadenectomy. Following adjustment the procedure was more likely in younger patients, those who presented with palpable adenopathy (cN1), those treated at an academic facility and those with a more contemporary diagnosis. On survival analysis controlling for all known and measured confounders inguinal lymphadenectomy was associated with improved overall survival (HR 0.79, 95% CI 0.74-0.84, p0.001).At hospitals that report to the National Cancer Database the overall rate of inguinal lymphadenectomy in patients with invasive penile cancer was only 27.2%. Inguinal lymphadenectomy was associated with increased overall survival, justifying the procedure as an important quality metric for performance reporting in patients with invasive penile cancer.

Background: Statin use is widespread among the general population. Data suggest a potentially beneficial effect of statin therapy on renal function following surgery. The impact of statins on post-partial nephrectomy (PN) renal function is unknown. We hypothesized that perioperative statin use may be associated with reduced rates of acute kidney injury (AKI) in patients undergoing PN. Objectives: To evaluate the effect of perioperative statin use on AKI rates in patients undergoing PN. Materials & Methods: 1,056 patients undergoing PN were identified from a prospectively-maintained institutional renal mass database. Exclusion criteria included lack of preoperative serum creatinine (Cr), concurrent surgeries, and those with baseline Cr

Introduction and objectives Renal mass biopsy (RMB) has not been widely adopted in evaluating small renal mass due to concerns for safety, efficacy, and its perceived lack of consequence on management decisions. We assess the potential cost savings and morbidity avoidance of routine RMB on cT1 renal masses undergoing robotic-assisted partial nephrectomy (RAPN). Methods We identified n = 920 consecutive RAPN pT1 renal masses and n = 429 consecutive RMBs for cT1 renal masses over 12 years. Using a novel pathological-based risk classification system for cT1 renal masses, we evaluated the morbidity and costs of our RAPN and RMB cohorts. We then define four clinical scenarios where RMB could potentially delay and/or avoid intervention in our pT1 RAPN cohort and model potential complications prevented and cost savings utilizing common clinical scenarios. Results Using our risk stratification system in RAPN patients, final histology was classified as benign in n=174 (18.9%) cases, very low-risk (n = 62 [7%]), low-risk (n = 383 [42%]), and high-risk (n = 301 [33%]), respectively. We identified n = 116 (12.6%) Clavien graded peri-operative complications. In our RMB patients, 120 (27.9%), 17 (3.9%), 240 (55.9%), 52(12.1%) were benign, very low, low and high-risk tumors. The median total direct cost for RAPN was $6955/case compared to $1312/case for RMB. If we established a primary goal to avoid immediate extirpative surgery in benign renal tumors, in the elderly (>70 y) with very low-risk tumors and/or those with high renal functional risks (≥ CKD3b), or competing risks (ASA ≥ 3), RMB could have reduced direct costs by approximately 20% and avoided n = 39 Clavien graded complications, seven readmissions, three transfusions, and two returns to the OR. With the additional cost of performing RMB on those not initially biopsied, the net cost saving would be approximately $1.2 million with minimal added complications while still treating high-risk tumors. Conclusions Routine RMB before intervention results in cost-saving and complication avoidance. Given the limitations of biopsy, shared decision-making is mandatory. Biopsy should be considered prior to intervention in at-risk populations.

Background: Early-onset renal cancer (eoRC) is typically associated with significant family history of cancer, and often associated with germline pathogenic variants (PVs) in ‘RC-specific' genes including VHL, MET, FLCN, TSC1, TSC2, FH, SDH, PTEN and BAP1. However, most eoRC patients lack PVs in RC-specific genes; rather, we recently identified an enrichment of likely PVs in DNA repair genes in eoRC patients. Here, using eoRC patient resources (primary and transformed lymphocytes, lymphocyte DNA, and tumor tissue), we functionally evaluated the DNA repair variants identified in eoRC patients. Methods: We performed whole-exome sequencing (WES) on lymphocyte DNA from 22 patients with genetically undefined eoRC, with extensive family history of RC and/or other cancers, provided by Risk Assessment Program and Genitourinary Group at Fox Chase Cancer Center. Prioritized variants were assessed by structural, biochemical and cellular studies. Results: 70% of patients had rare, heterozygous, missense variants in genes that suppress DNA damage. ~18% of the variants were in DNA polymerase genes (POLD1, POLE, POLH, POLK), which mediate DNA replication-repair. Increased tumor mutation burden (>10 mutations/Mb) was observed in tumors carrying predicted damaging polymerase variants. In functional testing, induction of DNA damage in primary lymphocytes from eoRC patients and matched cancer-free controls (n=20 each) selectively elevated γH2AX foci (indicative of DNA damage) in cells from eoRC patients (P Conclusion and future work: Our results indicate that germline variants in DNA repair genes impact suppression of DNA damage in cells from patients with eoRC. Biological studies testing the impact of the identified variants on renal carcinogenesis are warranted. Overall, genetic testing for variation in DNA repair genes may provide a more comprehensive risk assessment in eoRC patients, and provide novel opportunities for targeting DNA repair vulnerabilities in RC. Citation Format: Elena V. Demidova, Waleed Iqbal, Ilya G. Serebriiskii, Andrea F. Forman, Tatiana Kent, Richard T. Pomerantz, Erica A. Golemis, Michael J. Hall, David Y. Chen, Mary B. Daly, Sanjeevani Arora. Functional evaluation of novel germline DNA repair variants identified in patients with early-onset renal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 808.

Despite continued widespread use, the genomic effects of cisplatin-based chemotherapy and implications for subsequent treatment are incompletely characterized. Here, we analyze whole exome sequencing of matched pre- and post-neoadjuvant cisplatin-based chemotherapy primary bladder tumor samples from 30 muscle-invasive bladder cancer patients. We observe no overall increase in tumor mutational burden post-chemotherapy, though a significant proportion of subclonal mutations are unique to the matched pre- or post-treatment tumor, suggesting chemotherapy-induced and/or spatial heterogeneity. We subsequently identify and validate a novel mutational signature in post-treatment tumors consistent with known characteristics of cisplatin damage and repair. We find that post-treatment tumor heterogeneity predicts worse overall survival, and further observe alterations in cell-cycle and immune checkpoint regulation genes in post-treatment tumors. These results provide insight into the clinical and genomic dynamics of tumor evolution with cisplatin-based chemotherapy, suggest mechanisms of clinical resistance, and inform development of clinically relevant biomarkers and trials of combination therapies., The impact of cisplatin-based chemotherapy on tumor genomes is complex. Here, the authors study matched pre- and post-chemotherapy primary samples in muscle-invasive bladder cancer, finding a cisplatin-based mutational signature, and highlighting the impact of intratumor heterogeneity on survival.

Introduction To evaluate if interruptions of external beam radiation therapy impact outcomes in men with localized prostate cancer (PCa). Methods We included men with localized PCa treated with three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) of escalated dose (≥74 Gy in 1.8 or 2 Gy fractions) between 1992 and 2013 at an NCI-designated cancer centre. Men receiving androgen deprivation therapy were excluded. The non-treatment day ratio (NTDR) was defined as the number of non-treatment days divided by the total elapsed days of therapy. NTDR was analysed for each National Comprehensive Cancer Network (NCCN) risk group. Results There were 1728 men included (839 low-risk, 776 intermediate-risk and 113 high-risk), with a median follow up of 53.5 months (range 12–185.8). The median NTDR was 31% (range 23–71%), translating to approximately 2 breaks (each break represents a missed treatment that will be made up) for 8 weeks of RT with 5 treatments per week. The 75 percentile of NTDR was 33%, translating to approximately 4 breaks, which was used as the cutoff for analysis. There were no significant differences in freedom from biochemical failure, freedom from distant metastasis, cancer specific survival, or overall survival for men with NTDR ≥33% compared to NTDR

BACKGROUND The current study was performed to examine temporal trends and compare overall survival (OS) in patients undergoing radical cystectomy (RC) or bladder-preservation therapy (BPT) for muscle-invasive urothelial carcinoma of the bladder. METHODS The authors reviewed the National Cancer Data Base to identify patients with AJCC stage II to III urothelial carcinoma of the bladder from 2004 through 2013. Patients receiving BPT were stratified as having received any external-beam radiotherapy (any XRT), definitive XRT (50-80 grays), and definitive XRT with chemotherapy (CRT). Treatment trends and OS outcomes for the BPT and RC cohorts were evaluated using Cochran-Armitage tests, unadjusted Kaplan-Meier curves, adjusted Cox multivariate regression, and propensity score matching, using increasingly stringent selection criteria. RESULTS A total of 32,300 patients met the inclusion criteria and were treated with RC (22,680 patients) or BPT (9620 patients). Of the patients treated with BPT, 26.4% (2540 patients) and 15.5% (1489 patients), respectively, were treated with definitive XRT and CRT. Improved OS was observed for RC in all groups. After adjustments with more rigorous statistical models controlling for confounders and with more restrictive BPT cohorts, the magnitude of the OS benefit became attenuated on multivariate (any XRT: hazard ratio [HR], 2.115 [95% confidence interval [95% CI], 2.045-2.188]; definitive XRT: HR, 1.870 [95% CI, 1.773-1.972]; and CRT: HR, 1.578 [95% CI, 1.474-1.691]) and propensity score (any XRT: HR, 2.008 [95% CI, 1.871-2.154]; definitive XRT: HR, 1.606 [95% CI, 1.453-1.776]; and CRT: HR, 1.406 [95% CI, 1.235-1.601]) analyses. CONCLUSIONS In the National Cancer Data Base, receipt of BPT was associated with decreased OS compared with RC in patients with stage II to III urothelial carcinoma. Increasingly stringent definitions of BPT and more rigorous statistical methods adjusting for selection biases attenuated observed survival differences. Cancer 2017;123:4337-45. © 2017 American Cancer Society.

Background: Radical cystectomy is associated with perioperative complication rates exceeding 50% in some series. Readmission rates are increasingly used as a surgical quality metric. White blood cell count is a crude surrogate for physiologic processes which may reflect postoperative complications leading to readmission. Objective: We assessed the association between final white blood cell count at discharge and risk of readmission following radical cystectomy. Methods: Records on 477 patients undergoing radical cystectomy from 2006–2013 were reviewed. Final white blood cell count was defined as the last documented value during index admission. Univariate analysis was performed using Fisher’s exact, Wilcoxon rank sum test, and Spearman’s coefficient tests where appropriate. Multivariable logistic regression models were used to test the associations between final white blood cell count and readmission. Results: 34% of patients were readmitted within 90 days of surgery. Amongst this cohort, a cutoff final white blood cell count of 9000/mm3 was identified, with a significantly higher proportion of patients with values >9000/mm3 experiencing readmission than those with values≤9000/mm3 (42% vs 28%, p = 0.004). Other perioperative variables associated with an increased readmission rate included initial hospital length of stay≤10 days, and receipt of a continent diversion. Following adjustment, final white blood cell count >9000/mm3 was associated with increased risk of readmission (OR 2.09, 95% CI 1.23–3.53, p = 0.006). Conclusions: Final white blood cell count is associated with hospital readmission following radical cystectomy. This metric may provide important guidance in discharge algorithms.

BACKGROUND Patients with prostate cancer and their providers face uncertainty as they consider adjuvant radiotherapy (ART) or salvage radiotherapy (SRT) after undergoing radical prostatectomy. The authors prospectively evaluated the impact of the Decipher test, which predicts metastasis risk after radical prostatectomy, on decision making for ART and SRT. METHODS A total of 150 patients who were considering ART and 115 who were considering SRT were enrolled. Providers submitted a management recommendation before processing the Decipher test and again at the time of receipt of the test results. Patients completed validated surveys on prostate cancer (PCa)-specific decisional effectiveness and PCa-related anxiety. RESULTS Before the Decipher test, observation was recommended for 89% of patients considering ART and 58% of patients considering SRT. After Decipher testing, 18% (95% confidence interval [95% CI], 12%-25%) of treatment recommendations changed in the ART arm, including 31% among high-risk patients; and 32% (95% CI, 24%-42%) of management recommendations changed in the salvage arm, including 56% among high-risk patients. Decisional Conflict Scale (DCS) scores were better after viewing Decipher test results (ART arm: median DCS before Decipher, 25 and after Decipher, 19 [P

Penile cancer, most commonly squamous cell carcinoma (SCC), is rare in the United States and Europe but has an aggressive natural history. Due to disease rarity, randomized clinical trials demonstrating efficacious multimodal therapies for advanced disease are lacking. Multi-agent cisplatin-based neoadjuvant chemotherapy (NAC) utilizing the “TIP” regimen (paclitaxel, ifosfamide, and cisplatin) has demonstrated good clinical response rates in TxN2-3 disease.1 Clinical responders to NAC who undergo consolidative surgery show improved overall survival and time to progression. We present a case of invasive SCC of the penis with a bulky primary tumor and bilateral lymphadenopathy in a patient who refused initial penectomy. We discuss the role of NAC in this setting and our results employing multimodal therapy to facilitate a limited local excision.

Purpose: Rocapuldencel-T is an autologous immunotherapy prepared from mature monocyte-derived dendritic cells (DC), coelectroporated with amplified tumor RNA plus CD40L RNA. This pivotal phase III trial was initiated to investigate the safety and efficacy of a combination therapy dosing regimen of Rocapuldencel-T plus sunitinib in patients with metastatic renal cell carcinoma (mRCC). Patients and Methods: Patients received either Rocapuldencel-T plus standard of care (SOC) or SOC treatment alone. The primary objective compared overall survival (OS) between groups. Secondary objectives included safety assessments, progression-free survival (PFS), and tumor responses based on RECIST 1.1 criteria. Exploratory analyses included immunologic assessments and correlates with OS. Results: Between 2013 and 2016, 462 patients were randomized 2:1, 307 to the combination group and 155 to the SOC group. Median OS in the combination group was 27.7 months [95% confidence interval (CI) 23.0–35.9] and 32.4 months (95% CI, 22.5–) in the SOC group HR of 1.10 (95% CI, 0.83–1.40). PFS was 6.0 months and 7.83 months for the combination and SOC groups, respectively [HR = 1.15 (95% CI, 0.92–1.44)]. The ORR was 42.7% (95% CI, 37.1–48.4) for the combination group and 39.4% (95% CI, 31.6–47.5) for the SOC group. Median follow up was 29 months (0.4–47.7 months). On the basis of the lack of clinical efficacy, the ADAPT trial was terminated on February 17, 2017. Immune responses were detected in 70% of patients treated with Rocapuldencel-T, and the magnitude of the immune response positively correlated with OS. In addition, we report the survival-predictive value of measuring IL-12 produced by the DC vaccine and the observation that high baseline numbers of T regulatory cells are associated with improved outcomes in DC-treated patients, but are associated with poor outcomes in patients receiving SOC treatment. No serious adverse events attributed to the study medication have been reported to date. Conclusions: Rocapuldencel-T did not improve OS in patients treated with combination therapy, although the induced immune response correlated with OS. Moreover, we identified two potential survival-predictive biomarkers for patients receiving DC based immunotherapy, IL-12 produced by the DC vaccine and higher numbers of T regulatory cells present in the peripheral blood of patients with advanced RCC.

Purpose The optimal management of men with prostate cancer at high risk of recurrence postradical prostatectomy is controversial. The clinical utility of the Decipher test was evaluated prospectively on postoperative treatment decisions and patient-reported outcomes. Methods and Materials In the study, 246 eligible men across 19 centers were enrolled. Patients were dichotomized into those considering adjuvant or salvage radiation therapy (ART or SRT). Participating providers submitted a management recommendation before and after receiving the Decipher test results. Treatment received within 12 months and a validated survey on prostate cancer–related anxiety were collected longitudinally. Results Pre-Decipher, treatment was recommended for 12% and 40% for the ART and SRT arms, respectively. Post-Decipher, 17% and 30% of treatment recommendations changed in the ART and SRT arms, respectively. Post-Decipher treatment recommendation was administered 78% and 76% of the time in the ART and SRT arms, respectively. Multivariable analysis confirmed that the Decipher score was an independent predictor for change in management for both adjuvant and salvage patients. The number needed to test to change management for one patient was 4. Cancer-specific anxiety decreased among Decipher risk categories in both arms. Conclusions Use of Decipher postradical prostatectomy test was associated with postoperative treatment decisions. Overall, high Decipher risk was associated with an increase in treatment intensity whereas low risk scores were associated with a decrease in therapy administered independent of clinical and pathologic risk factors.

The Gleason scoring system is a key component of a prostate cancer diagnosis, since it indicates disease aggressiveness. It also serves as a risk communication tool that facilitates shared treatment decision-making. However, the system is highly complex and therefore difficult to communicate: factors which have been shown to undermine well-informed and high-quality shared treatment decision-making. To systematically explore prostate cancer patients’ understanding of the Gleason scoring system (GSS), we assessed knowledge and perceived importance among men who had completed treatment (N = 50). Patients were administered a survey that assessed patient knowledge and patients’ perceived importance of the GSS, as well as demographics, medical factors (e.g., Gleason score at diagnosis), and health literacy. Bivariate analyses were conducted to identify associations with patient knowledge and perceived importance of the GSS. The sample was generally well-educated (48% with a bachelor’s degree or higher) and health literate (M = 12.9, SD = 2.2, range = 3–15). Despite this, patient knowledge of the GSS was low (M = 1.8, SD = 1.4, range = 1–4). Patients’ understanding of the importance of the GSS was moderate (M = 2.8, SD = 1.0, range = 0–4) and was positively associated with GSS knowledge (p

INTRODUCTION AND OBJECTIVES:The AIM and ReM were recently introduced to objectify fusion biopsy deliverables. The AIM metric affords a quantifiable assessment of when US/MRI fusion targeted biopsy ...

397 Background: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by cystectomy (Cx) or chemoradiation (CRT) is the standard of care for urothelial carcinoma (UC) pts with muscle invasive bladder cancer (MIBC). Both Cx and CRT have potential short and long-term toxicity and QOL implications. Mutations in DNA damage repair/response genes are associated with pathologic downstaging after NAC. Methods: We conducted a phase II, multi-institutional clinical trial (NCT02710734) to evaluate a risk-adapted approach to treatment of MIBC. Pts with cT2-T3N0M0 UC of the bladder, ECOG PS 0-1 and CrCl≥50 mL/min, underwent NAC with accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC). Pre-NAC TURBT specimens were sequenced (Caris Life Sciences) for mutations (pathogenic or VUS) in ATM, ERCC2, FANCC or RB1. Pts with at least one mutation and no clinical evidence of disease by restaging TUR and imaging post-NAC began pre-defined active surveillance (AS). Remaining pts underwent bladder-directed therapy: intravesical therapy ( < cT2 post-NAC), CRT or Cx. The primary endpoint was metastasis-free survival (MFS) at 2 years which is not mature. We herein report key interim results of clinically-meaningful intermediate endpoints. Results: Seventy-one (ITT) pts were enrolled over 33 months at four academic centers. Median age was 70 years (47-83), 74% were male, 92% Caucasian, 81% ECOG PS 0 and 79% cT2. 90% completed 3 cycles of NAC and with 17% grade 3-4 TRAEs and one death during AMVAC. At the time of data cut-off (September 11, 2020), for the ITT pts, 32 pts have had a Cx, 5 underwent CRT and 7 underwent intravesical therapy, at some point during the trial. Thirty-three pts (46%) had a mutation of interest and 28 pts (39%) started AS (2 of the 28 pts on AS did not have a mutation but elected to start AS after achieving cT0 post AMVAC). 76% of those with a mutation were cT0 at post-NAC TURBT. With a median follow-up of 14.9 mo (range: 3.1-35.3 mo), 14 AS pts recurred (50%). Of the 14 recurrences, 2 recurred with locally advanced or metastatic disease and have died, 5 had MIBC with one eventual metastatic recurrence, and 7 had NMIBC. Six (14%) non-AS pts have died. Out of the 40 pts who did not go to upfront Cx [AS (N = 28), CRT (N = 5), intravesical tx (N = 7)], 3 (7.5%) (all in the AS group) went on to Cx later. The bladder preservation rate is 55% for ITT pts and 89% for the AS group. In the AS cohort, mutations were seen in RB1 (50%), ATM (42%), ERCC2 (31%), FANCC (4%) with lowest rate for recurrence in ERCC2 (25% recurrence) vs RB1 (62% recurrence). Conclusions: Interim results of a phase II trial of risk enabled therapy utilizing a selection of clinical and genomic factors in pts with cT2-T3 MIBC demonstrates a 50% rate of any UC recurrence and a 11% rate of locally advanced/metastatic disease in the AS group. 89% of AS pts have retained their bladder. Follow-up continues for the primary endpoint of 2-year MFS. Clinical trial information: NCT02710734.

BACKGROUND Approximately 50% of newly diagnosed cancer patients start taking dietary supplements. Men's health supplements (MHSs), which we define as supplements that are specifically marketed with the terms men's health and prostate health (or similar permutations), are often mislabeled as having potential anticancer benefits. OBJECTIVE We evaluated the effects of MHSs on patient outcomes and toxicities in patients who were undergoing definitive intensity-modulated radiation therapy (IMRT) for localized prostate cancer. DESIGN This retrospective analysis included patients who were being treated at a National Cancer Institute-designated comprehensive cancer center and consented to have information stored in a prospective database. MHSs were queried online. Outcome measures were freedom from biochemical failure (FFBF) (biochemical failure was defined with the use of the prostate-specific antigen nadir + 2-ng/mL definition), freedom from distant metastasis (FFDM), cancer-specific survival (CSS), and overall survival (OS) as well as toxicities. Kaplan-Meier analysis, log-rank tests, Fine and Gray competing-risk regression (to adjust for patient and lifestyle factors), and Cox models were used. RESULTS From 2001 to 2012, 2207 patients were treated with IMRT with a median dose of 78 Gy, and a median follow-up of 46 mo. Of these patients, 43% were low risk, 37% were intermediate risk, and 20% were high risk; 10% used MHSs. MHSs contained a median of 3 identifiable ingredients (range: 0-78 ingredients). Patients who were taking an MHS compared with those who were not had improved 5-y OS (97% compared with 92%, respectively; P = 0.01), but there were no differences in the FFBF (94% compared with 89%, respectively; P = 0.12), FFDM (96% compared with 97%, respectively; P = 0.32), or CSS (100% compared with 99%, respectively; P = 0.22). The unadjusted association between MHS use and improved OS was attenuated after adjustment for patient lifestyle factors and comorbidities. There was no difference in toxicities between the 2 groups (late-grade 3-4 genitourinary

The purpose of this study was to evaluate if time to treatment (TTT) has an effect on outcomes for patients with localized prostate cancer treated with definitive external beam radiation therapy (EBRT).We included 4064 patients (1549 low-risk, 1612 intermediate-risk, and 903 high-risk) treated with EBRT. For each National Comprehensive Cancer Network (NCCN) risk group, TTT (defined as the time between initial positive prostate biopsy and start of RT) was analyzed in 4 intervals: 3, 3-6, 6-9, and 9-24 months. We recorded the use of androgen deprivation therapy among patients with intermediate-risk and high-risk disease.The median TTT was 3.3 months (range, 0.6-23.5 months), and it was similar for each risk group (range, 3.3-3.4 months). The median follow up was 64 months. There were no significant differences in biochemical failure, distant metastasis, or overall survival for patients with TTT 3, 3-6, 6-9, or 9-24 months for each risk group. There were also no significant differences in the outcomes at 5 years when patients with TTT3.3 months were compared with those with TTT ≤ 3.3 months for each risk group. For high-risk men, 328 of 450 (72.9%) with TTT3.3 months were on androgen deprivation therapy (ADT) versus 299 of 453 (66%) with TTT ≤ 3.3 months. Among men with high-risk cancer treated without ADT, there remained no significant difference in outcomes between TTT3.3 months and TTT ≤ 3.3 months.TTT was not associated with significant differences in outcomes among each risk group of men with localized prostate cancer treated with EBRT. Among the high-risk patients, there were no observed detriments in outcomes with TTT3.3 months regardless of androgen deprivation therapy use.

Sarcomatoid changes in renal cell carcinoma are associated with a poor prognosis. The identification of genetic alterations that drive this aggressive phenotype could aid in the development of more effective targeted therapies. In this study we aimed to pinpoint unique copy number alterations in sarcomatoid renal cell carcinoma compared to classical renal cell carcinoma subtypes.Genomic copy number analysis was performed using single nucleotide polymorphism based microarrays on tissue extracted from the tumors of 81 patients who underwent renal mass excision, including 17 with sarcomatoid renal cell carcinoma.Sarcomatoid renal cell carcinoma showed a significantly higher number of copy number alterations than clear cell, papillary and chromophobe renal cell carcinoma (mean 18.0 vs 5.8, 6.5 and 7.2, respectively, p0.0001). Copy number losses of chromosome arms 9q, 15q, 18p/q and 22q, and gains of 1q and 8q occurred in a significantly higher proportion of sarcomatoid renal cell carcinomas than in the other 3 histologies. Patients with sarcomatoid renal cell carcinoma demonstrated significantly worse overall survival compared to those without that condition on Kaplan-Meier analysis (p = 0.0001). Patients with 9 or more copy number alterations also demonstrated significantly worse overall survival than those with fewer than 9 copy number alterations (p = 0.004).Sarcomatoid changes in renal cell carcinoma are associated with a high rate of chromosomal imbalances with losses of 9q, 15q, 18p/q and 22q, and gains of 1q and 8q occurring at significantly higher frequencies in comparison to nonsarcomatoid renal cell carcinoma. Identifying candidate driver genes or tumor suppressor loci in these chromosomal regions may help identify targets for future therapies.

523 Background: Neoadjuvant cisplatin-based chemotherapy (NAC) followed by cystectomy is the standard of care for muscle-invasive urothelial bladder cancer (MIBC). 15-35% of MIBC patients present with ureteral obstruction. Poor renal function increases cisplatin toxicity. It is unknown whether patients with ureteral obstruction which has been relieved (whether by nephrostomy tube or nephroureteral stent) have the same risk of toxicity as patients without ureteral obstruction. Methods: We retrospectively reviewed an institutional database of all patients undergoing NAC for MIBC with either dose dense MVAC (ddMVAC) or gemcitabine and cisplatin (GC) from January 2004 through May 2017. Patients without ureteral obstruction prior to initiation of NAC (Group A) were compared to those who had ureteral obstruction which was relieved prior to undergoing NAC (Group B). Continuous variables were compared using the Wilcoxon rank-sum test and categorical variables were compared using Fisher’s exact test. The primary outcome was premature discontinuation of NAC, which was defined as failure to complete all planned cycles. Logistic regression was used to test for differences between the groups in this outcome adjusting for age, ECOG performance status, and baseline glomerular filtration rate (GFR). Results: 160 patients in Group A and 59 patients in Group B were identified. Baseline age, Charlson Comorbidity Index, race, smoking status, and ECOG performance status were similar. Patients in Group B had lower GFR (99.2% vs 78.8% p