Renal Medullary Carcinoma: The Zebra Amongst the Horses.

A 13-year old Latino male presented with recurrent gross hematuria, 5cm right-sided poorly defined heterogeneous mass, enlarged retrocaval lymph nodes, and 1.2 cm paratracheal lymph node. Given the need for multiple blood transfusions, robot-assisted radical nephrectomy with lymph node dissection was performed. Pathology revealed pT3a high-grade tumor, clear margins, and positive lymph node. Additionally, with multiple sickled RBCs and loss of staining of SMARCB1 in tumor specimen, and hemoglobin electrophoresis suggesting sickle cell trait, diagnosis of metastatic renal medullary carcinoma was confirmed. The patient was enrolled into COG AREN 03B2 trial, and has completed 10 cycles of carboplatin/gemcitabine/bortezomib alternating with cisplatin/gemcitabine/paclitaxel, with no evidence of recurrent disease 9 months post-surgery.

Intermediate-Term Oncologic Outcome Assessment for Robot-Assisted Radical Prostatectomy: Comparing Retzius-Sparing with Standard Approach in a Randomized Control Cohort.

Introduction: Retzius-sparing prostatectomy was promoted with the early continence result. The long-term oncologic outcome is still unknown. In this study, we aimed to compare the intermediate-term oncologic outcomes of these two approaches in patients' cohort who were treated as part of a randomized controlled trial. Methods: A total of 120 patients were previously randomized equally to receive Retzius-sparing robot-assisted laparoscopic radical prostatectomy (RS-RARP) vs standard robot-assisted laparoscopic radical prostatectomy (S-RARP) between January 2015 and April 2016. Baseline, surgical, and pathologic characteristics as well as oncologic outcomes were assessed. The analysis was done based on the treatment received. Result: Sixty-three patients underwent S-RARP, whereas 57 patients underwent RS-RARP. There was no statistically significant difference in the baseline nor surgical characteristics. The median follow-up was 71.24 (interquartile range: 59.75-75.75) months. There were more pathologic T3 diseases in RS-RARP. There was no significant difference in the positive margin status nor in the biochemical recurrence (BCR) rate among both groups. After S-RARP and RS-RARP, 6 and 10 patients had BCR, and the 5 years BCR-free survival was 91% and 85%, respectively (p = 0.21). Conclusion: In this cohort, there was no difference in BCR in the patients who received either technique. Further multi-institutional studies with a larger sample size and longer follow-up are required.

Prostate Specific Antigen Screening on a Nationwide Level: Featuring the Contribution of Race and Life Expectancy in Decision Making.

BACKGROUND: Estimation of life expectancy (LE) is important for the relative benefit of prostate specific antigen (PSA) screening. Limited data exists regarding screening for Black men with extended LE. The aim of the current study was to assess temporal trends in screening in United States (US) Black men with limited vs. extended LE, using a nationally representative dataset. MATERIALS AND METHODS: Using the National Health Institution Survey (NHIS) 2000 to 2018, men aged ≥40 without prior history of prostate cancer (PCa) who underwent PSA screening in the last 12 months were stratified into limited LE (ie, LE <15 years) and extended LE (ie, LE≥15 years) using the validated Schonberg index. LE-stratified temporal trends in PSA screening were analyzed for all men, and then in Black men. Weighted multivariable analyses and dominance analyses identified the predictors of PSA screening. RESULTS: PSA screening declined over the study period both for all eligible men with limited and extended LE, particularly between NHIS 2008 and 2013 (27.9%-20.7% in the extended). Screening increased significantly in Black men with extended LE (17.6% in 2010-25.7% in 2018). However, LE was not an independent predictor of screening in the Black cohort. Prior recipient of colonoscopy (55%-57%) and visit to health care provider (24%-32%) were the most important determinants for screening. CONCLUSION: For US men with extended LE, only 1 in 4 receive PSA screening, with a decline over the study-period. Screening rates increased for Black men. However, these changes were not driven by LE consideration itself, but participation in other screenings and access to a provider.

Temporal and Racial Trends in Prostate-specific Antigen Screening for U.S. Men With a Family History of Prostate Cancer.

INTRODUCTION: Limited data exist on trends in PSA screening in men with a family history of prostate cancer. The aims of our study were to (1) study age-stratified temporal trends in PSA screening from 2000-2018 for men with a family history of prostate cancer and Black men with a family history of prostate cancer, and (2) identify determinants associated with receipt of PSA screening in the aforementioned groups. METHODS: We identified men aged ≥40 years without a prior history of prostate cancer using data from National Health Interview Survey 2000-2018 who self-reported PSA testing in the last 12 months. Age-stratified temporal trends and weighted multivariable logistic regression analyses were assessed. RESULTS: PSA screening increased for men with a family history of prostate cancer between National Health Interview Survey 2000 (28.9%) and 2005 (41.9%), with stable rates for the following years. Black men with a family history of prostate cancer showed no significant change in PSA screening rates regardless of age. Controlling for sociodemographics and access to health care provider, younger age (40-54) and later survey years (2013-2018) were associated with a lower likelihood of PSA screening overall and for Black men, but not for those with a positive family history. CONCLUSIONS: Data from a nationally representative study of U.S. men indicated that the annual PSA screening rates for men with a family history of prostate cancer was higher than reported for the overall male population. We believe this represents the first study on trends and determinants of PSA screening in U.S. men with a family history of prostate cancer.

Who Is Shaping the Future of Academic Urology? A Descriptive Analysis of Residency Program Directors.

OBJECTIVE: To characterize the demographics, educational background, and scholarly characteristics of current urology residency program directors (PDs). METHODS: Urology programs were identified by the listing on the "Accredited US Urology Programs" section of American Urological Association website as of October 2021. Demographics and academic data were collected via publicly available department website and Google search engine. Metrics obtained included years of service as PD from time of appointment, sex, medical school/residency/fellowship, all-time H-index, dual degrees obtained, and professorial ranking. RESULTS: One hundred and forty-seven accredited urological residencies were reviewed; every PD was included. The majority were male (78%) and fellowship trained (68%). Women represented only 22% of PDs. The median active time served as PD, as of 11/2021, was 4years (IQR: 2-7). Forty (28%) were faculty at the same program they completed their residency. The median all-time H-index was 12 (IQR: 7-19; range 1-61). Twelve PDs also served as chair of their department. CONCLUSION: The vast majority of PDs are male, fellowship trained, and have served for less than 5years. Future studies are necessary to follow the trends of representation in leaders of urology residency programs.

Time to second biochemical recurrence as a prognostic indicator in postprostatectomy patients who undergo salvage radiation therapy: An RTOG 9601 based post hoc analysis.

INTRODUCTION AND OBJECTIVE: The prognostic significance of a "second" biochemical recurrence (sBCR) after salvage radiation therapy (sRT) with/without hormonal therapy following primary radical prostatectomy in men with prostate cancer has not been examined. We hypothesized that a shorter time to sBCR will be associated with worse cancer control outcomes. METHODS: The RTOG 9601 study included 760 patients with tumor stage pT2/T3, pN0, who had either persistently elevated prostate-specific antigen (PSA) postradical prostatectomy or developed subsequent biochemical recurrence with PSA levels between 0.2 and 4.0 ng/ml. All patients received sRT (with or without 2 years of Bicalutamide) from 1998 to 2015. For our study, we focused on 421 patients who had sBCR after sRT-which was defined as a PSA increase of at least 0.3 ng/ml over the first nadir. Patients were divided into two categories: early sBCR (n = 210) and late sBCR (n = 211) using median time to sBCR (3.51 years). All patients who experienced sBCR received salvage hormonal therapy. Competing-risk analysis was used to examine the impact of early versus late sBCR on prostate cancer specific mortality (CSM), after accounting for available covariates. RESULTS: The majority of patients were age 60 years or older (75.8%), had pT3 disease (74.8%), and Gleason score 7 (75.2%). Overall, 13.8% had persistent PSA initially after surgery. At 10 years, starting at the time of sBCR, CSM rate was 31.3% in the early sBCR group versus 20.0% in the late sBCR group. In competing-risk analysis, time to sBCR was an independent predictor of CSM, where patients with early sBCR had 1.7-fold higher CSM risk (p = 0.026) than their counterparts with late sBCR. CONCLUSIONS: Time to sBCR after sRT (with or without concomitant Bicalutamide) is a significant predictor of CSM following initial radical prostatectomy. This information can be used to guide subsequent treatments, and to counsel patients.

A novel prognostic model predicting overall survival in patients with metastatic castration-resistant prostate cancer receiving standard chemotherapy: A multi-trial cohort analysis.

PURPOSE: Generalizable, updated, and easy-to-use prognostic models for patients with metastatic castration-resistant prostate cancer (mCRPC) are lacking. We developed a nomogram predicting the overall survival (OS) of mCRPC patients receiving standard chemotherapy using data from five randomized clinical trials (RCTs). METHODS: Patients enrolled in the control arm of five RCTs (ASCENT 2, VENICE, CELGENE/MAINSAIL, ENTHUSE 14, and ENTHUSE 33) were randomly split between training (n = 1636, 70%) and validation cohorts (n = 700, 30%). In the training cohort, Cox regression tested the prognostic significance of all available variables as a predictor of OS. Independent predictors of OS on multivariable analysis were used to construct a novel multivariable model (nomogram). The accuracy of this model was tested in the validation cohort using time-dependent area under the curve (tAUC) and calibration curves. RESULTS: Most of the patients were aged 65-74 years (44.5%) and the median (interquartile range) follow-up time was 13.9 (8.9-20.2) months. At multivariable analysis, the following were independent predictors of OS in mCRPC patients: sites of metastasis (visceral vs. bone metastasis, hazard ratio [HR]: 1.24), prostate-specific antigen (HR: 1.00), aspartate transaminase (HR: 1.01), alkaline phosphatase (HR: 1.00), body mass index (HR: 0.97), and hemoglobin (≥13 g/dl vs. <11 g/dl, HR: 0.41; all p < 0.05). A nomogram based on these variables was developed and showed favorable discrimination (tAUC at 12 and 24 months: 73% and 72%, respectively) and calibration characteristics on external validation. CONCLUSION: A new prognostic model to predict OS of patients with mCRPC undergoing first line chemotherapy was developed. This can help urologists/oncologists in counseling patients and might be useful to better stratify patients for future clinical trials.

Risk-Based Assessment Of the Impact Of Intravesical Therapy on Recurrence-Free Survival Rate Following Resection of Suspected Low-grade, Non-muscle-invasive Bladder Cancer (NMIBC): A Southwest Oncology Groups (SWOG) S0337 Posthoc Analysis.

BACKGROUND: Nonmuscle invasive bladder cancer (NMIBC) has an elevated risk of recurrence, and immediate postresection intravesical instillation of chemotherapy (IVC) significantly reduces the risk of recurrence. Questions remain about which subpopulation may maximally benefit from IVC. Our aim was to develop risk groups based on recurrence risk in NMIBC, and then evaluate the impact of a single, postoperative instillation of IVC on the subsequent risk of recurrence for each risk group. MATERIAL AND METHODS: Using the SWOG S0337 trial cohort, we performed a posthoc analysis of 345 patients who were diagnosed with suspected low-grade NMIBC, underwent transurethral resection of the bladder tumor (TURBT), and received post-operative IVC (gemcitabine vs. saline). Using regression tree analysis, the regression tree stratified patients based on their risk of recurrence into low-risk - single tumor and aged < 57 years, intermediate-risk - single tumor and aged ≥ 57 years, and high-risk - multiple tumors. We used Cox proportional hazard models to test the impact of recurrence-free rate, and after adjustment to available covariates. RESULTS: Median age of the cohort was 66.5 (IQR: 59.7-75.8 years) with 85% of patients being males. Median overall follow-up time was 3.07 years (IQR: 0.75-4.01 years). When testing the impact of treatment in each risk group separately, we found that patients in the intermediate-risk treated with gemcitabine had a 24-month recurrence free rate of 77% (95% CI: 68%-86%) vs. 59% (95% CI: 49%-70%) in the saline group. This survival difference was confirmed on multivariable analysis (hazard ratio: 0.39, 95% CI: 23%-66%, P < 0.001). This group represented 53% of our cohort. Conversely, we did not observe a significant difference in recurrence-free survival among patients in the low- (P = 0.7) and high-risk (P = 0.4) groups. CONCLUSION: Our findings indicate that older patients with a single tumor of suspected low-grade NMIBC at TURBT maximally benefit from immediate postresection IVC (gemcitabine).

Evaluation of lymphovascular invasion as a prognostic predictor of overall survival after radical prostatectomy.

OBJECTIVE: To assess the prognostic ability of lymphovascular invasion (LVI) as a predictor of overall survival (OS). MATERIALS AND METHODS: We included 126,682 prostate cancer (CaP) cM0 patients who underwent radical prostatectomy with lymph node dissection between 2010 and 2015, within the National Cancer Database. Patients who received androgen deprivation therapy were included. Patients were divided into four sub-cohorts based on LVI and lymph node invasion (LNI) status: pL0N0, pL1N0, pL0N1, and pL1N1. Kaplan-Meier curves estimated OS and Cox-regression analysis tested the relationship between LVI and OS. RESULTS: Median (IQR) age and PSA at diagnosis were 62 (57-66) years and 5.7 (4.5-8.9) ng/ml, respectively. Most patients had pT2 stage (68.5%), and pathological Gleason 3+4 (46.7%). 10.0% and 4.0% patients had LVI and LNI, respectively. Median follow-up was 42 months (27-58). At 5-years, OS was 96.5% in pL0N0 patients vs 93.1% pL1N0 patients vs 93.3% in pL0N1 patients vs 86.6% pL1N1 patients. LVI was an independent predictor of OS (hazard ratio [HR]:1.28). LVI showed interaction with LNI, as LVI was associated with a higher overall-mortality in patients with LNI (HR:1.66), than in patients without LNI (HR:1.22). (all P<0.0001) CONCLUSIONS: Our report highlights the detrimental impact of LVI on OS. Patients with LVI alone fared similarly to patients with LNI alone. Patients with both LVI and LNI had worse OS than those with only LVI or LNI, implying a synergetic detrimental interaction. Our findings demonstrate an important utility that LVI can provide in deciding patients' prognoses.

External validation of genomic classifier-based risk-stratification tool to identify candidates for adjuvant radiation therapy in patients with prostate cancer.

OBJECTIVE: To externally validate a Genomic Classifier (GC) based risk-stratification nomogram identifying candidates who would benefit from adjuvant radiation (aRT) therapy after radical prostatectomy (RP). METHODS: We identified 350 patients who underwent RP, between 2013 and 2018, and had adverse pathological features (positive margin, and/or pT3a or higher) on final pathology. Genomic profile was available for all these men. The clinical recurrence-free survival was estimated using the Kaplan-Meier method. The external validity of the nomogram was tested using the concordance index (c-index), calibration plot, and decision curve analysis. RESULTS: The median follow-up of the cohort was 26.5 months. Overall, 14% of the patients received aRT. During the follow-up period, 3.4% of the patients developed metastasis. Overall 3-year metastasis-free survival was 95% (95% CI 0.92-0.98). The c-index of the nomogram was 0.84. The calibration of the model was favorable. Decision-curve analysis showed a positive net benefit for probabilities ranging between 0.01 and 0.09, with the highest difference at threshold probability around 0.05. At that threshold, the net benefit is 0.06 for the model and 0 for treating all the patients. CONCLUSION: Our report is the first to confirm the validity of this genomic-based risk-stratification tool in identifying men who might benefit from aRT after RP. As such, it can be a useful instrument to be incorporated in shared decision making on whether administration of aRT will lead to a clinically meaningful benefit. Such a model can also be useful for patients' classification in future clinical trials.

Impact of treatment modality on overall survival in localized ductal prostate adenocarcinoma: A national cancer database analysis.

PURPOSE: Ductal adenocarcinoma is considered a rare histological variant of prostate adenocarcinoma (PCa). Given the rarity of this subtype, optimal treatment strategies for men with nonmetastatic ductal PCa is largely unknown. We aimed to describe the impact of surgery, radiotherapy, systemic therapy, and observation on overall survival (OS) in men with nonmetastatic ductal PCa. MATERIALS AND METHODS: We selected 1,656 cases of nonmetastatic ductal PCa, diagnosed between 2004 and 2015, within the National Cancer Database. Covariates included age, race, Charlson comorbidity score, clinical T stage, clinical lymph node stage, serum prostate specific antigen (PSA), income, hospital type, insurance status, year of diagnosis, and location of residence. Cox regression analysis tested the impact of treatment (surgery, radiotherapy, systemic therapy, and observation) on OS. RESULTS: In men with nonmetastatic ductal PCa, median (interquartile range [IQR]) age and PSA were 67 (60-73) years and 6.2 (4.2-10.7) ng/ml, respectively. Advanced local stage (≥cT3a) was most frequently observed in patients initially treated with systemic therapy (34.8%), followed by those treated with radiotherapy (18.1%), surgery (7.1%) and observation (6.4%, P< 0.001). Serum PSA at presentation was highest in the systemic therapy cohort (median 16.0 ng/ml, IQR: 4.9-37.7), followed by the radiotherapy cohort (median 7.2 ng/ml, IQR: 4.1-12.2), observation cohort (median 7.0 ng/ml, IQR: 4.3-13.3) and surgery cohort (median 5.9 ng/ml, IQR: 4.3-9.2, P< 0.001). Multivariable analysis showed that in comparison to men treated surgically, OS was significantly lower for patients receiving radiotherapy (HR 2.2; 95% CI: 1.5-3.2), under observation (HR 4.6; 95% CI: 2.8-7.6) and receiving systemic therapy (HR 5.2; 95% CI: 3.0-9.1) as an initial course of treatment. CONCLUSIONS: While limited by its retrospective nature, our study shows that starting treatment with surgery is associated with more favorable long-term OS outcomes than radiotherapy, systemic therapy or observation.

A Nationwide Persistent Underutilization of Adjuvant Radiotherapy in North American Prostate Cancer Patients.

OBJECTIVE: To examine the utilization of adjuvant radiotherapy (aRT) in contemporary prostate cancer patients with adverse pathological features at radical prostatectomy (RP). METHODS: We identified 189,240 patients with adverse features at RP (positive margin, stage ≥pT3a, and/or pN1 disease), from 2004 to 2015, within the National Cancer Database, and validated our findings within Surveillance, Epidemiology, and End Results (SEER) program. We examined the utilization of patients with aRT with adverse features at RP and patients with very aggressive disease (at least 2 of the following: ≥pT3b, pathological Gleason 8-10, and pN1). Regression analysis examined the relationship of various predictors of utilization adjusting to confounders. Pseudo R2 analysis examined the magnitude of influence that each variable had on the decision to use aRT. RESULTS: Within the National Cancer Database cohort, only 11.7% of our patients received aRT. In patients with very aggressive disease, aRT utilization rate was 28.9%. Within the SEER cohort, 16.3% of patients with any adverse features at time of RP received aRT. In patients with very aggressive disease, only 30% of patients received aRT. Further, year of diagnosis, Gleason grade, pathologic stage, and positive surgical margin were the variables that had the greatest influence on the decision to use aRT, and that positive surgical margin, type of institution at which care was received, and lymph node involvement were the most influential variables in patients with very aggressive disease. CONCLUSIONS: The current standard of care in the United States represents a significant underutilization of aRT in eligible patients with prostate cancer. Urgent efforts are necessary to address this quality-of-care concern.

Managing Urology Consultations During COVID-19 Pandemic: Application of a Structured Care Pathway.

OBJECTIVE: To describe and evaluate a risk-stratified triage pathway for inpatient urology consultations during the SARS-CoV-2 (COVID-19) pandemic. This pathway seeks to outline a urology patient care strategy that reduces the transmission risk to both healthcare providers and patients, reduces the healthcare burden, and maintains appropriate patient care. MATERIALS AND METHODS: Consultations to the urology service during a 3-week period (March 16 to April 2, 2020) were triaged and managed via one of 3 pathways: Standard, Telemedicine, or High-Risk. Standard consults were in-person consults with non COVID-19 patients, High-Risk consults were in-person consults with COVID-19 positive/suspected patients, and Telemedicine consults were telephonic consults for low-acuity urologic issues in either group of patients. Patient demographics, consultation parameters and consultation outcomes were compared to consultations from the month of March 2019. Categorical variables were compared using Chi-square test and continuous variables using Mann-Whitney U test. A P value <.05 was considered significant. RESULTS: Between March 16 and April 2, 2020, 53 inpatient consultations were performed. By following our triage pathway, a total of 19/53 consultations (35.8%) were performed via Telemedicine with no in-person exposure, 10/53 consultations (18.9%) were High-Risk, in which we strictly controlled the urology team member in-person contact, and the remainder, 24/53 consultations (45.2%), were performed as Standard in-person encounters. COVID-19 associated consultations represented 18/53 (34.0%) of all consultations during this period, and of these, 8/18 (44.4%) were managed successfully via Telemedicine alone. No team member developed COVID-19 infection. CONCLUSION: During the COVID-19 pandemic, most urology consultations can be managed in a patient and physician safety-conscious manner, by implementing a novel triage pathway.

Ten-year disease progression and mortality rates in men who experience biochemical recurrence versus persistence after radical prostatectomy and undergo salvage radiation therapy: A post-hoc analysis of RTOG 9601 trial data.

PURPOSE: To compare local/metastatic disease progression and overall mortality rates in men with node-negative prostate cancer at radical prostatectomy (RP) that experience biochemical recurrence vs. persistence postoperatively and undergo salvage radiation therapy (sRT). MATERIALS AND METHODS: Data on 760 men who participated in the RTOG 9601 trial were extracted using the NCTN data archive platform. Patients were stratified into biochemical recurrence (nadir-PSA ≤0.4 ng/ml) or persistence (nadir-PSA >0.4 ng/ml) groups, based on the cut-off reported in the original trial. Inverse probability of treatment weighting (IPTW) methodology was utilized to minimize the baseline differences among groups. Competing-risk and Kaplan-Meier analyses estimated the impact of prostate-specific antigen (PSA) persistence vs. recurrence on local and metastatic disease progression and overall-mortality in the IPTW-adjusted model; a 2-sided P < 0.05 was considered significant. RESULTS: All patients received sRT, and about 50% of the patients in either group received concomitant antiandrogen therapy (P = 0.951). The median follow-up was 12 years. After IPTW, the 2 groups were well-matched with standardized mean differences ∼10%. In the IPTW-adjusted cohort, the 10-year local and metastatic disease occurrence rates were 3.2% vs. 1.4% (Gray's P = 0.0001) and 28.6% vs. 10.1% (Gray's P < 0.0001) in patients with persistent vs. recurrent PSA, respectively. Similarly, the 10-year overall-mortality rates were 24.9% vs. 11.9% (Log-rank P = 0.029), respectively. CONCLUSIONS: Patients with biochemical persistence after RP are approximately 2.5 times more likely to experience local/metastatic failure and death, compared to patients with biochemical recurrence after RP, despite equivalent sRT with/without antiandrogen therapy use. These data may facilitate patient counseling and shared treatment selection.