Germline Pathogenic Variants Identified in Patients With Genitourinary Malignancies Undergoing Universal Testing: A Multisite Single-Institution Prospective Study.

PURPOSE: This study aimed to investigate the prevalence of pathogenic germline variants (PGVs) in hereditary cancer genes utilizing a universal testing approach and to determine the rate of PGVs that would have been missed based on National Comprehensive Cancer Network (NCCN) guidelines in genitourinary (GU) malignancies. MATERIALS AND METHODS: A multisite, single-institution prospective germline genetic test (GGT) was universally offered to patients with new or active diagnoses of GU malignancies (prostate, bladder, and renal) from April 2018 to March 2020 at Mayo Clinic sites. Participants were offered GGT using a next-generation sequencing panel of > 80 genes. Demographic, tumor characteristics, and genetic results were evaluated. NCCN GU cancer guidelines were used to identify whether patients had incremental findings, defined as PGV-positive patients who would not have received testing based on NCCN guidelines. RESULTS: Of 3095 individuals enrolled in the study, 601 patients had GU cancer (prostate = 358, bladder = 106, and renal = 137). The mean enrollment age was 67 years (SD 9.1), 89% were male, and 86% of patients were non-Hispanic White. PGVs were identified in 82 (14%) of all GU patients. PGV prevalence breakdown by cancer type was: 14% prostate, 14% bladder, and 13% renal cancer. Nearly one-third of identified PGVs were high penetrance, and the majority of these (67%) were clinically actionable. Incremental PGVs were identified in 28 (57%) prostate, 15 (100%) bladder, and 14 (78%) renal cancer patients. Of the 82 patients with PGV findings, 29 (35%) had at least 1 relative undergo cascade testing for the familial variant(s) identified. CONCLUSIONS: More than 1 in 8 patients with GU malignancies were found to carry a PGV, with 67% of patients with high-penetrance PGVs undergoing clinically actionable changes. The majority of these PGVs would not have been identified based on current testing criteria. These findings support universal GGT for GU malignancies and underscore its potential to enhance risk assessment and guide precision interventions in urologic oncology.

Bacillus Calmette-Guerin (BCG) therapy is safe and effective in non-muscle invasive bladder cancer (NMIBC) patients with immunomodulating conditions.

INTRODUCTION: Bacillus Calmette-Guerin (BCG) is the most effective therapy available to treat high-risk nonmuscle invasive bladder cancer (NMIBC) patients. However, for patients with immunomodulating conditions BCG is a relative contraindication due to efficacy and safety concerns. To our knowledge, no population-level study evaluating the efficacy and safety profile of BCG for immunomodulated patients exists. METHODS: NMIBC patients aged 66 years or older were identified in the Surveillance, Epidemiology, and End Results (SEER) - Medicare database from 1975-2013. All patients completed adequate BCG (at least 5 plus 2 treatments completed within 12 months of diagnosis). Two groups were defined: an immunomodulated population identified by immunomodulating conditions such as solid-organ transplantation, HIV, and autoimmune conditions, and an immunocompetent group. The primary endpoint was 5-year progression-free survival defined as progression to systemic chemotherapy, checkpoint inhibitors, radical or partial cystectomy, metastasis, or cancer-specific death. A safety analysis was performed as a secondary outcome. RESULTS: In a total of 4,277 patients with NMIBC who completed adequate BCG, 606 (14.2%) were immunomodulated. The immunomodulated group was older at diagnosis (P < 0.001), more likely to be female (P < 0.001), more likely to live in a metropolitan area (P < 0.001), and had higher Charlson comorbidity scores (P < 0.001). There were no differences in progression to chemotherapy (P = 0.17), checkpoint inhibitors (P > 0.99), radical cystectomy (P = 0.40), partial cystectomy (P = 0.93), metastasis (P = 0.19), cancer-specific death (P = 0.18) or 5-year total bladder cancer progression (P = 0.30) between the groups. For the safety analysis, rates of disseminated BCG were similar between immunomodulated and immunocompetent patients (0.7% vs. <1.8%, P = 0.51). On multivariable analysis 5-year total bladder cancer progression (HR 1.07 [CI 0.88-1.30]) was similar between the groups. CONCLUSION: Rates of bladder cancer progression and disseminated BCG complications 5-years after BCG therapy were similar regardless of immunomodulation status. These findings suggest that BCG intravesical therapy can be offered to immunomodulated patients with high-risk NMIBC although theoretical infectious complication risks remain.

Greater Obstetric Barriers for Female Urologists Compared to Peer-Physicians.

OBJECTIVE: To determine the prevalence of pregnancy complications, infertility, and maternal support for female urologists in comparison to the general population and other female physicians. METHODS: An anonymous, voluntary survey was distributed to female physicians via private physician social media groups from June to August 2021. The survey queried pregnancy demographics and complications, infertility diagnosis and treatment, workplace environment, and prior education on these topics. Results were compared between urologists and the general population and other female physicians with Fisher exact test, chi-square with Yates's correction, or Student's t tests as indicated. RESULTS: Four thousand six hundred twelve female physicians completed the survey including 241 (5%) urologists. Compared with the general population, urologists were more likely to have a miscarriage or preterm birth, have children later in life, and undergo infertility evaluation or infertility treatment (all P < .0001). 42% of urologists reported experiencing a pregnancy complication and only 9% of those surveyed received education on the risks of delaying pregnancy. Despite being educated more often regarding the risks of delaying pregnancy compared to other physicians, urologists were less likely to have children, had fewer children, and were more likely to be discouraged from starting a family during training and practice (all P < .0001). Additionally, urologists reported shorter parental leave, worked more hours per week while pregnant, and were less likely to receive lactation accommodations compared to other female physicians (all P < .001). CONCLUSION: Education for trainees on family planning and fostering a culture of support are deficits identified in overcoming obstetric barriers in urologists.

Surgical Site Infections in Open and Laparoscopic Operations in Rooms With Open-floor Drainage Systems.

INTRODUCTION: Surgical site infections are common postoperative complications. Some operating rooms have open-floor drainage systems for fluid disposal during endourologic cases, although nonendoscopy cases are not always allowed in these rooms. We hypothesized that operating rooms with open-floor drainage systems would not materially affect risk of surgical site infections for patients undergoing open and laparoscopic procedures. METHODS: Patients who had surgical site infections from 2016 through 2020 were identified from data of the National Surgical Quality Improvement Program. Patients without surgical incisions, with open wounds, and with surgical site infections at surgery were excluded. The primary outcome was surgical site infection occurrence within 30 days of surgery. Multilevel multivariable logistic regression was used to estimate the observed-to-expected surgical site infection ratio for each operating room (2 with and 23 without open-floor drainage systems). RESULTS: We identified 8,419 surgical cases, of which 802 (9.5%) were performed in operating rooms with open-floor drainage systems; 166 patients (2.0%) had surgical site infections. Of the surgical site infections, 7 (4.2%) occurred in operating rooms with open-floor drainage systems. Surgical specialty, American Society of Anesthesiologists physical status, higher case acuity, dyspnea, immunosuppression, longer surgical duration, and wound classification were associated with surgical site infections (P < .05 for all). The observed-to-expected ratios of surgical site infections occurring in the 2 operating rooms with open-floor drainage systems were 0.85 and 1.15. The odds ratio of surgical site infections for urologic cases performed in room with vs without open-floor drainage systems was 1.30 (P = .65). CONCLUSIONS: Urology operating room designs often include open-floor drainage systems for water-based cases. These drainage systems were not associated with an increased risk of surgical site infections.

A comparison of naloxegol versus alvimopan at the time of cystectomy and urinary diversion.

INTRODUCTION: The use of alvimopan at the time of cystectomy has been associated with improved perioperative outcomes. Naloxegol is a less costly alternative that has been used in some centers. This study aims to compare the perioperative outcomes of patients undergoing cystectomy with urinary diversion who receive the mu-opioid antagonist alvimopan versus naloxegol. MATERIALS AND METHODS: This was a retrospective review that included all patients who underwent cystectomy with urinary diversion at our institution between 2007-2020. Comparisons were made between patients who received perioperative alvimopan, naloxegol and no mu-opioid antagonist (controls). RESULTS: In 715 patients who underwent cystectomy, 335 received a perioperative mu-opioid antagonist, of whom 57 received naloxegol. Control patients, compared to naloxegol and alvimopan patients, experienced a significantly (p < 0.05) delayed return of bowel function (4.3 vs. 2.5 vs. 3.0 days) and longer hospital length of stay (7.9 vs. 7.5 vs. 6.5 days), respectively. The incidence of nasogastric tube use (14.2% vs. 12.5% vs. 6.5%) and postoperative ileus (21.6% vs. 21.1% vs. 13.3%) was also most common in the control group compared to the naloxegol and alvimopan cohorts, respectively. A multivariable analysis revealed that when comparing naloxegol and alvimopan, there was no difference in return of bowel function (OR 0.88, p = 0.17), incidence of postoperative ileus (OR 1.60, p = 0.44), or hospital readmission (OR 1.22, p = 0.63). CONCLUSIONS: Naloxegol expedites the return of bowel function to the same degree as alvimopan in cystectomy patients. Given the lower cost of naloxegol, this agent may be a preferable alternative to alvimopan.

BCG Administration after Prior Radiation Treatment for Prostate Cancer.

INTRODUCTION: Prostate radiotherapy is associated with worse oncologic outcomes in patients with bladder cancer. The underlying mechanism is incompletely understood but is thought to be related to an altered microenvironment promoting tumorigenesis. However, there is a gap in the literature regarding how the effect of BCG varies according to prior radiotherapy in patients with non-muscle invasive bladder cancer (NMIBC). In this context, we sought to evaluate oncologic outcomes in NMIBC patients who have previously undergone prostate radiotherapy compared to patients with no prior history of pelvic radiotherapy. METHODS: This is a retrospective cohort study that includes all patients who received intravesical for NMIBC at our institution from 2001 to 2019. Patients were stratified into 3 cohorts: prior radiotherapy (RT), radical prostatectomy (RP), and no prostate cancer (No PCa). The outcomes of interest were recurrence at 1-year, progression to muscle-invasive bladder cancer (MIBC), and progression to metastatic disease. Comparisons were also made between cohorts with respect to elapsed time from radiation therapy. Wilcoxon rank-sum test was used for comparing continuous variables, while χ2 and Fischer's exact tests were used to examine categorical variables. RESULTS: In 199 total patients who underwent BCG for NMIBC, 23 had a prior history of prostate radiotherapy treatment, while 17 underwent prior radical prostatectomy. Overall, 41.2% of patients had recurrence at 1 year. There was no difference in the number of induction or maintenance BCG administrations received between the cohorts within the first year. There was no significant difference in recurrence at 1 year between the 3 cohorts (P = .56). There was also no difference in progression to MIBC or progression to metastatic disease with P = .50 and 0.89, respectively. CONCLUSION: The risk of recurrence after induction BCG treatment for high-grade NMIBC does not vary according to prior radiation treatment for prostate cancer.

Salvage versus primary holmium laser enucleation of the prostate: trends, outcomes and safety analysis.

PURPOSE: To study the safety, efficacy and trends in index procedures leading to salvage holmium laser enucleation of the prostate (S-HoLEP). METHODS: This was a single-institution retrospective review of HoLEPs performed between 2006 and 2020. Patients who underwent S-HoLEP were compared to those undergoing primary holmium laser enucleation of the prostate (P-HoLEP). The endpoint of primary interest were functional outcomes. Changes in index procedures over the study period were analyzed. RESULTS: A total of 633 HoLEPs were performed during the study, with 217 being S-HoLEP. The S-HoLEP cohort was older than P-HoLEP cohort, 71.2 years vs 68.8 years (p = 0.03). All other factors were well matched. The most common index procedures prior to S-HoLEP included transurethral resection of the prostate (TURP) (87, 40.1%), transurethral microwave thermotherapy (TUMT) (44, 20.3%), photoselective vaporization of the prostate (PVP) (24, 11.1%) and prostatic urethral lift (PUL) (24, 11.1%). Preoperative prostate volume, IPSS and Qmax were similar between groups. Intra-operatively, S-HoLEP had longer procedure and morcellation times (p = 0.01 and 0.007). Postoperatively, the S-HoLEP cohort had longer catheter duration and hospitalization (both p < 0.001). Postoperative Qmax, IPSS and 90-day complication rates were similar. On temporal analysis, minimally invasive surgical therapies (MIST) have become more prevalent as index procedures. CONCLUSION: S-HoLEP is safe and efficacious for patients requiring additional BPH surgical intervention. S-HoLEP patients had longer operative times and hospital stays but equivalent postoperative functional outcomes compared to P-HoLEP. As MIST mature and gain traction, it is expected that rates of S-HoLEP will continue to rise.

Hemostatic agent use during partial nephrectomy: trends, outcomes, and associated costs.

PURPOSE: To evaluate the ability of hemostatic agents (HA) to limit bleeding complications following partial nephrectomy (PN) and determine HA usage and costs as well as factors associated with post-operative bleeding complications. METHODS: The records of 429 PN performed for kidney cancers were reviewed for clinical, pathologic, and perioperative variables. Surgical approach, HA use, and HA expenditure were determined. Bleeding complications and management to 90 days after PN were annotated. Wilcoxon rank-sum and two-sample t tests identified factors associated with HA use. Univariate and limited multivariate logistic regression determined variables associated with bleeding complications. RESULTS: Use of HA was associated with longer OR duration, longer ischemia time, higher EBL, and method of PN (OPN and LPN > RPN) (all p values < 0.001). On bivariate analysis, while multiple factors were associated with bleeding complications, neither HA use (p = 0.924) nor the number of HA used (two agents vs one p = 0.712; three agents vs. one p = 0.606) were. A multivariable model noted that increasing RENAL score (p = 0.013) and surgical approach (OPN vs. RPN [p = 0.009] and LPN vs. RPN (p = 0.002]) were independently associated with bleeding complications, while HA use was not (p = 0.294). During the 16 years of analysis, a total of $77,687 USD was spent on HA. Average annual HA expenditure was $4855 USD with the peak being in 2010 where expense was $14,086. Mean annual costs for HA use were greater for OPN vs RAPN starting in 2013 (p = 0.02) CONCLUSIONS: The use of HA during PN was not associated with lower rates of bleeding complications. Therefore, judicious use in a case-specific manner is requisite to limit potentially unnecessary operative cost.