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Abstract Prostate cancer is the second most common cancer in men and affects 1 in 9 men in the United States. Early screening for prostate cancer often involves monitoring levels of prostate-specific antigen (PSA) and performing digital rectal exams. However, a prostate biopsy is always required for definitive cancer diagnosis. The Early Detection Research Network (EDRN) is a consortium within the National Cancer Institute aimed at improving screening approaches and early detection of cancers. As part of this effort, the Weill Cornell EDRN Prostate Cancer has collected and biobanked specimens from men undergoing a prostate biopsy between 2008 and 2017. In this report, we describe blood metabolomics measurements for a subset of this population. The dataset includes detailed clinical and prospective records for 580 patients who underwent prostate biopsy, 287 of which were subsequentially diagnosed with prostate cancer, combined with profiling of 1,482 metabolites from plasma samples collected at the time of biopsy. We expect this dataset to provide a valuable resource for scientists investigating prostate cancer metabolism.

Abstract Background Ultra-hypofractionated image-guided stereotactic body radiotherapy (SBRT) is increasingly used for definitive treatment of localized prostate cancer. Magnetic resonance imaging-guided radiotherapy (MRgRT) facilitates improved visualization, real-time tracking of targets and/or organs-at-risk (OAR), and capacity for adaptive planning which may translate to improved targeting and reduced toxicity to surrounding tissues. Given promising results from NRG-GU003 comparing conventional and moderate hypofractionation in the post-operative setting, there is growing interest in exploring ultra-hypofractionated post-operative regimens. It remains unclear whether this can be done safely and whether MRgRT may help mitigate potential toxicity. SHORTER (NCT04422132) is a phase II randomized trial prospectively evaluating whether salvage MRgRT delivered in 5 fractions versus 20 fractions is non-inferior with respect to gastrointestinal (GI) and genitourinary (GU) toxicities at 2-years post-treatment. Methods A total of 136 patients will be randomized in a 1:1 ratio to salvage MRgRT in 5 fractions or 20 fractions using permuted block randomization. Patients will be stratified according to baseline Expanded Prostate Cancer Index Composite (EPIC) bowel and urinary domain scores as well as nodal treatment and androgen deprivation therapy (ADT). Patients undergoing 5 fractions will receive a total of 32.5 Gy over 2 weeks and patients undergoing 20 fractions will receive a total of 55 Gy over 4 weeks, with or without nodal coverage (25.5 Gy over 2 weeks and 42 Gy over 4 weeks) and ADT as per the investigator’s discretion. The co-primary endpoints are change scores in the bowel and the urinary domains of the EPIC. The change scores will reflect the 2-year score minus the pre-treatment (baseline) score. The secondary endpoints include safety endpoints, including change in GI and GU symptoms at 3, 6, 12 and 60 months from completion of treatment, and efficacy endpoints, including time to progression, prostate cancer specific survival and overall survival. Discussion The SHORTER trial is the first randomized phase II trial comparing toxicity of ultra-hypofractionated and hypofractionated MRgRT in the salvage setting. The primary hypothesis is that salvage MRgRT delivered in 5 fractions will not significantly increase GI and GU toxicities when compared to salvage MRgRT delivered in 20 fractions. Trial registration ClinicalTrials.gov Identifier: NCT04422132. Date of registration: June 9, 2020.

BACKGROUND Prostate cancer is multifocal with distinct molecular subtypes. The utility of genomic subtyping has been challenged due to inter- and intrafocal heterogeneity. We sought to characterize the subtype-defining molecular alterations of primary prostate cancer across all tumor foci within radical prostatectomy (RP) specimens and determine the prevalence of collision tumors.METHODS From the Early Detection Research Network cohort, we identified 333 prospectively collected RPs from 2010 to 2014 and assessed ETS-related gene (ERG), serine peptidase inhibitor Kazal type 1 (SPINK1), phosphatase and tensin homolog (PTEN), and speckle type BTB/POZ protein (SPOP) molecular status. We utilized dual ERG/SPINK1 immunohistochemistry and fluorescence in situ hybridization to confirm ERG rearrangements and characterize PTEN deletion, as well as high-resolution melting curve analysis and Sanger sequencing to determine SPOP mutation status.RESULTS Based on index focus alone, ERG, SPINK1, PTEN, and SPOP alterations were identified in 47.5%, 10.8%, 14.3%, and 5.1% of RP specimens, respectively. In 233 multifocal RPs with ERG/SPINK1 status in all foci, 139 (59.7%) had discordant molecular alterations between foci. Collision tumors, as defined by discrepant ERG/SPINK1 status within a single focus, were identified in 29 (9.4%) RP specimens.CONCLUSION Interfocal molecular heterogeneity was identified in about 60% of multifocal RP specimens, and collision tumors were present in about 10%. We present this phenomenon as a model for the intrafocal heterogeneity observed in previous studies and propose that future genomic studies screen for collision tumors to better characterize molecular heterogeneity.FUNDING Early Detection Research Network US National Cancer Institute (NCI) 5U01 CA111275-09, Center for Translational Pathology at Weill Cornell Medicine (WCM) Department of Pathology and Laboratory Medicine, US NCI (WCM SPORE in Prostate Cancer, P50CA211024-01), R37CA215040, Damon Runyon Cancer Research Foundation, US MetLife Foundation Family Clinical Investigator Award, Norwegian Cancer Society (grant 208197), and South-Eastern Norway Regional Health Authority (grant 2019016 and 2020063).

Summary: Men diagnosed with low-risk prostate cancer (PC) are increasingly electing active surveillance (AS) as their initial management strategy. While this may reduce the side effects of treatment for PC, many men on AS eventually convert to active treatment. PC is one of the most heritable cancers, and genetic factors that predispose to aggressive tumors may help distinguish men who are more likely to discontinue AS. To investigate this, we undertook a multi-institutional genome-wide association study (GWAS) of 5,222 PC patients and 1,139 other patients from replication cohorts, all of whom initially elected AS and were followed over time for the potential outcome of conversion from AS to active treatment. In the GWAS we detected 18 variants associated with conversion, 15 of which were not previously associated with PC risk. With a transcriptome-wide association study (TWAS), we found two genes associated with conversion (MAST3, p = 6.9 × 10−7 and GAB2, p = 2.0 × 10−6). Moreover, increasing values of a previously validated 269-variant genetic risk score (GRS) for PC was positively associated with conversion (e.g., comparing the highest to the two middle deciles gave a hazard ratio [HR] = 1.13; 95% confidence interval [CI] = 0.94–1.36); whereas decreasing values of a 36-variant GRS for prostate-specific antigen (PSA) levels were positively associated with conversion (e.g., comparing the lowest to the two middle deciles gave a HR = 1.25; 95% CI, 1.04–1.50). These results suggest that germline genetics may help inform and individualize the decision of AS—or the intensity of monitoring on AS—versus treatment for the initial management of patients with low-risk PC.

Upper tract urothelial carcinoma (UTUC) is an aggressive cancer and largely uncharacterised cancer. Here, Faltas and colleagues report its distinctive molecular and immune landscape compared to urothelial carcinoma of the bladder and explore the role of FGFR3 signaling in UTUC biology.

ObjectiveTo analyze population-level changes in operative practice since the onset of the COVID-19 pandemic to contextualize observations made by individual practices and optimize future responses.Materials and MethodsThis US retrospective analysis used the Premier Perspectives Database. We investigated changes in operative volume through March 2020. Baseline operative volume for urologic surgery was calculated using data from the preceding 12 months and compared on a total and by procedure basis. Multivariable linear regression was used to identify hospital-level predictors of change in response to the pandemic.ResultsAt baseline, we captured 23,788 urologic procedural encounters per month as compared with 19,071 during March 2020– a 19.9% decrease. Urologic oncology-related cases were relatively preserved as compared to others (average change in March 2020: +1.1% versus -32.2%). Northeastern (β = -5.66, 95% confidence interval [CI]: -10.2 to -1.18, p = 0.013) and Midwestern hospitals (β = -4.17, 95% CI: -7.89 to -0.45, p = 0.027; both with South as reference region), and those with an increasing percentage of patients insured by Medicaid (β= -0.17 per percentage point, 95% CI: -0.33 to -0.01, p = 0.04) experienced a significantly larger decrease in volume.ConclusionsThere was a 20% decline in urologic operative volume in March 2020, compared with baseline, that preferentially affected hospitals serving Medicaid patients, and those in Northeast and Midwest. In the face of varying mandates on elective surgery, widespread declines in operative volume may also represent hesitancy on behalf of patients to interface with healthcare during the pandemic.

Robot-assisted radical cystectomy (RARC) is an emerging operative alternative to open surgery for the management of invasive bladder cancer. Studies from single institutions provide limited data due to the small number of patients. In order to better understand the related outcomes, a world-wide consortium was established in 2006 of patients undergoing RARC, called the International Robotic Cystectomy Consortium (IRCC). Thus far, the IRCC has reported its findings on various areas of operative interest and continues to expand its capacity to include other operative modalities and transform it into the International Radical Cystectomy Consortium. This article summarizes the findings of the IRCC and highlights the future direction of the consortium.

Purpose. To date, no study has examined a population-based registry to determine the impact of multiple malignancies on survival of bladder cancer patients. Our experience suggests that bladder cancer patients with multiple malignancies may have relatively positive outcomes. Materials & Methods. We utilized data from the Surveillance Epidemiology and End Results (SEERs) database to examine survival between patients with only bladder cancer (BO) and with bladder cancer and additional cancer(s) antecedent (AB), subsequent (BS), or antecedent and subsequent to bladder cancer (ABS). Results. Analyses demonstrated diminished survival among AB and ABS cohorts. However, when cohorts were substratified by stage, patients in the high-stage BS cohort appeared to have a survival advantage over high-stage BO patients. Conclusions. Bladder cancer patients with multiple malignancies have diminished survival. The survival advantage of high-stage BS patients is likely a statistical phenomenon. Such findings are important to shape future research and to improve our understanding of patients with multiple malignancies.

Background and PurposeSince the advent of immunosuppressive therapy, patients have been able to lead longer lives as transplant recipients. We report the first case of robot-assisted laparoscopic prostatectomy in the renal allograft recipient.Patients and MethodsA 54-year-old man presented with Gleason 33 localized prostate cancer with a prostatespecific antigen level of 8.5 ngmL. He had a history of end-stage renal failure secondary to fulminant acute pyelonephritis necessitating bilateral nephrectomy. Renal allograft transplant in the right iliac fossa was performed in 1981, with adequate renal function while continuing his immunosuppressant regime. The patient also had previous left inguinal herniorrhaphy. Modifications to our surgical approach include placement of a bariatric port superiolaterally to the standard port site; siting the left port inferiolaterally to provide adequate access for pelvic lymph node dissection; and developing the retropubic space largely from the contralateral side to avoid allograft injury. Extensive adhesiolysis was also needed. After negative urethral margin reported on frozen section, vesicourethral anastomosis was fashioned using our Cornell bladder neck anatomic reconstruction technique.ResultsThe patient needed a postoperative transfusion of 1 unit of blood and was discharged on postoperative day 2 after recommencement of immunosuppression. The final pathology report revealed pT2cGleason 7 (34) disease and negative surgical margins. Continence was recovered within the first week of catheter removal, and erections sufficient for penetration occurred before 6-week follow-up in the clinic.ConclusionRobot-assisted radical prostatectomy is feasible in the carefully selected renal allograft recipient with favorable oncologic, continence, and potency outcomes. [ABSTRACT FROM AUTHOR]

The Rex-1 (Zfp-42) gene encodes a zinc finger family transcription factor which is highly expressed in mouse and human embryonic stem cells. It is one of several gene markers used to identify human stem cells. While several organs are known to harbor adult human stem cells, the presence and distribution of stem cells in both the normal and neoplastic adult kidney remains largely unknown. In this study we evaluated Rex-1 mRNA and protein expression in normal and malignant kidney tissue specimens from human patients. Rex-1 mRNA expression was determined using both reverse transcription and real-time PCR. REX1 protein expression was assessed by western analysis and immunohistochemistry, using an affinity-purified, polyclonal antibody to the REX1 protein. We found that 14 of 15 (93%) non-tumor renal parenchymal specimens demonstrated Rex-1 mRNA, compared with 5 of 14 (36%) renal tumors (P < 0.005). REX1 protein expression was detected in 21 of 23 (91%) non-tumor and in 7 of 19 (37%) tumor specimens (P < 0.001). Furthermore, in six of these seven renal tumor specimens where REX1 protein expression was detected, the levels were at least 3-fold lower than those in adjacent, normal kidney tissue. There were no differences in Rex-1 mRNA or protein expression among the various histologic subtypes of renal tumors (clear cell carcinoma, papillary carcinoma, chromophobe carcinoma and oncocytoma). Immunohistochemical staining confirmed the absence of REX1 in three renal tumor specimens (two clear cell and one papillary carcinoma), while the REX1 protein was detected in a small percentage of proximal tubular cells in normal renal tissue. Immunohistochemical staining of another stem cell marker, OCT4, demonstrated a similar pattern of protein expression in a small percentage of normal renal proximal tubular cells. In summary, we were able to detect Rex-1 mRNA and protein expression in over 90% of normal renal parenchymal specimens and we observed a significant reduction in REX1 expression in renal tumor specimens of all histologic subtypes. [ABSTRACT FROM AUTHOR]

Purpose: Clinical guidelines have recently included renal mass biopsy (RMB) in management algorithms, especially in the setting of small renal masses ≤ 4 cm (SRM) and ablative therapy. We sought to evaluate the diagnostic rates of RMB, factors associated with a non-diagnostic biopsy, its clinical utility, and its safety profile in the setting of ablative therapy. Materials and Methods: A total of 174 RMB from 167 patients, performed in a tertiary academic center from 01/2015 to 01/2019, were included. Patient demographics, radiographic mass size, RMB diagnoses, subsequent clinical management, and complications were retrospectively reviewed. RMBs were classified as diagnostic or non-diagnostic based on set criteria. Results: The mean mass size was 3.0 cm (range: 0.5-15.3 cm) and 140 biopsies (80%) were SRM. Among all RMB, 159 (91%) were diagnostic and 15 (9%) were non-diagnostic. Non-diagnostic biopsies were associated with small mass size, the presence of a cystic component (p < 0.00001) and fewer number of cores submitted (p = 0.0046). All non-diagnostic biopsies occurred in SRMs, where the mean mass size was significantly smaller than diagnostic biopsies (1.3 versus 3.2 cm, p = 0.001). RMB with concurrent ablation yielded non-diagnostic results more frequently than isolated RMBs (15% vs 2%, respectively). Conclusions: RMB is useful for definitive diagnosis and clinical management in the setting of ablative therapy. Small mass size, cystic lesions, and fewer number of passes obtained are associated with non-diagnostic biopsies. When a renal mass diagnosis is particularly critical, a separate biopsy procedure prior to ablative therapy is recommended.

PurposeTo validate prognostic factors and determine the impact of obesity, hypertension, smoking and diabetes mellitus (DM) on risk of recurrence after surgery in patients with localized renal cell carcinoma (RCC).Materials and methodsWe performed a retrospective cohort study among patients that underwent partial or radical nephrectomy at Weill Cornell Medicine for RCC and collected preoperative information on RCC risk factors, as well as pathological data. Cases were reviewed for radiographic evidence of RCC recurrence. A Cox proportional-hazards model was developed to determine the contribution of RCC risk factors to recurrence risk. Disease-free survival and overall survival were analyzed using the Kaplan-Meier method and log-rank test.ResultsWe identified 873 patients who underwent surgery for RCC between the years 2000-2015. In total 115 patients (13.2%) experienced a disease recurrence after a median follow up of 4.9 years. In multivariate analysis, increasing pathological T-stage (HR 1.429, 95% CI 1.265-1.614) and Nuclear grade (HR 2.376, 95% CI 1.734-3.255) were independently associated with RCC recurrence. In patients with T1-2 tumors, DM was identified as an additional independent risk factor for RCC recurrence (HR 2.744, 95% CI 1.343-5.605). Patients with DM had a significantly shorter median disease-free survival (1.5 years versus 2.6 years, p = 0.004), as well as median overall survival (4.1 years, versus 5.8 years, pConclusionsWe validated high pathological T-stage and nuclear grade as independent risk factors for RCC recurrence following nephrectomy. DM is associated with an increased risk of recurrence among patients with early stage disease.