Adverse events in men with advanced prostate cancer treated with androgen biosynthesis inhibitors and androgen receptor inhibitors.

BACKGROUND: The use of androgen biosynthesis and second-generation androgen receptor inhibitors for advanced prostate cancer is increasing. Because these therapies alter the androgen pathway, they have been associated with cardiometabolic and neurocognitive toxicities. Although their safety profiles have been assessed in clinical trials, real-world data are limited. METHODS: A 20% sample of national Medicare claims was used to perform a retrospective cohort study of Medicare beneficiaries with advanced prostate cancer treated with androgen biosynthesis (ie, abiraterone) and second-generation androgen receptor inhibitors between 2012 and 2019. Outcomes were assessed after the first fill of either class of drug for the 12-month period after starting therapy. The primary outcome was a hospital admission or emergency department visit for a cardiometabolic event. Secondary outcomes included neurocognitive events and fractures. Multivariable regression was used to assess the association between the class of drug and occurrence of an adverse event. RESULTS: There were 3488 (60%) men started on an androgen biosynthesis inhibitor and 2361 (40%) started on an androgen receptor inhibitor for the first time. Cardiometabolic adverse events were more common in men managed with androgen biosynthesis inhibitor (9.2% vs 7.5%, P = .027). No difference between androgen biosynthesis and androgen receptor inhibitors was observed for neurocognitive events (3.3% vs 3.4%, respectively; P = .71) or fractures (4.2% vs 3.6%, respectively; P = .26). CONCLUSIONS: Men with advanced prostate cancer initiating an androgen biosynthesis inhibitor for the first time more commonly had cardiometabolic events than those started on androgen receptor inhibitors. Neurocognitive events and fractures did not differ by drug class.

Out-of-pocket costs for diagnostic testing following abnormal prostate cancer screening among privately insured men.

OBJECTIVE: Prostate cancer is the most common malignancy among men and following a positive prostate-specific antigen (PSA) screening test, patients may undergo more expensive diagnostic testing. However, testing-related out-of-pocket costs (OOPCs), which may preclude patients from completing the screening process, have not been previously quantified. OOPCs for follow-up diagnostic testing (i.e., prostate biopsy and/or magnetic resonance imaging [MRI]) in patients with private insurance undergoing prostate cancer screening were estimated. METHODS: Men ages 55 to 69 years old who underwent PSA-based prostate cancer screening from 2010 to 2020 from the IBM Marketscan database were identified. The number of patients undergoing follow-up diagnostic testing within 12 months of screening was tabulated, dividing patients into three groups: (1) biopsy only, (2) MRI only, and (3) MRI + biopsy. Over the study period, patients with nonzero cost-sharing and calculated inflation-adjusted OOPCs, adding copayment, coinsurance, and deductible payments, for each group were identified. RESULTS: Among screened patients (n = 3,075,841) from 2010 through 2020, 91,850 had a second PSA test and an elevated PSA level, of which 40,329 (43.9%) underwent subsequent diagnostic testing. More than 75% of these patients experienced cost-sharing, and median OOPCs rose substantially over the study period for patients undergoing biopsy only ($79 to $214), MRI only ($81 to $490), and MRI and biopsy ($353 to $620). CONCLUSIONS: OOPCs from diagnostic testing after prostate cancer screening are common and rising. This work aligns with the recent position statement from the American Cancer Society, that payers should eliminate cost-sharing, which may undermine the screening process, for diagnostic testing following cancer screening.

Variations in germ cell tumor histology by age and implications for cancer-specific survival among pediatric and adult males: A population-based study.

PURPOSE: Few studies have quantified differences in histology and implications for survival between male children and adults with germ cell tumors (GCT). We evaluated these differences and associations with cancer-specific survival (CSS) using Surveillance, Epidemiology, and End Results (SEER) cancer registries. METHODS: SEER (1988-2016) was used to identify male patients 0 to 40 years of age diagnosed with seminoma and nonseminomatous GCT (NSGCT). Demographic and tumor characteristics were tabulated with histology distributions compared by age group (0-4, 12-18, 19-40 years old). CSS was evaluated in multivariable Cox proportional hazards regression models. RESULTS: Among 27,204 patients identified, 1,538 (5.7%) were pediatric (0-18 years). Seminoma (54.3%) predominated in adult patients (ages 19-40). Among 0 to 4 years-old, yolk sac tumor (71.2%) and teratoma (21.5%) were most common. Mixed GCT (52.7%) was most prevalent among 12 to 18 years-old with seminoma, embryonal, and teratoma occurring in 12 to 15% each. Relative to pediatric patients, adult patients had similar CSS for seminoma but worse CSS for NSGCT on Kaplan-Meier curves with 9 years mean follow-up. Choriocarcinoma and yolk sac tumors carried the worst prognosis relative to seminoma for both children (HR 5.7 and HR 11.1, respectively, both P < 0.01) and adults (HR 4.6 and HR 4.6, respectively, both P < 0.01) adjusted for stage. CONCLUSION: Histology of GCTs vary by age with yolk sac tumors and teratoma predominating for male patients 0 to 4 years, mixed GCT for 12 to 18 years, and seminoma for 19 to 40 years. Pediatric patients with NSGCT had higher CSS than their adult counterparts. Mixed GCT represented an increasing proportion of GCT over the study period. Age, stage, and histology impact CSS in both pediatric and adult populations.

Teaching Hospitals and Textbook Outcomes After Major Urologic Cancer Surgery.

OBJECTIVE: To assess textbook outcomes by hospital teaching status following major surgery for urologic cancers. METHODS: We used 100% national Medicare Provider Analysis and Review files from 2017-2020 to assess rates of textbook outcomes in patients undergoing bladder (ie, radical cystectomy), kidney (ie, radical or partial nephrectomy), and prostate (ie, radical prostatectomy) surgery for genitourinary malignancies. The extent of integration of learners into each hospital's workforce-defined as major, minor, and non teaching hospitals-was the primary exposure. A textbook outcome, measured at the patient level, was defined as the absence of in-hospital mortality and mortality within 30days of surgery, no readmission 30days following discharge, no postoperative complication, and no prolonged length of stay. RESULTS: Textbook outcomes were achieved in 51% (8564/16,786) of patients after bladder cancer surgery, 70% (39,938/57,300) of patients after kidney cancer surgery, and 82% (50,408/61,385) of patients after prostate cancer surgery. After adjusting for patient- and hospital-level characteristics, teaching hospitals had higher rates of textbook outcomes in those undergoing bladder (50.7% vs 44.0%; P = .001), kidney (72.0% vs 69.7%; P = .02), and prostate (85.3% vs 81.0%; P <.001) surgery. This effect was attenuated, but not eliminated, by surgical volume in additional sensitivity analyses for bladder (OR: 1.20, 95% CI: 1.00-1.42; P = .04) and prostate (OR: 1.15, 95% CI: 1.00-1.32; P = .04) surgery. There were no significant differences in kidney cancer surgery outcomes after adjusting for hospital volume (OR: 1.03, 95% CI: 0.93-1.14; P = .6). CONCLUSION: Undergoing major cancer surgery at a teaching hospital was associated with an increased likelihood of achieving a textbook outcome. This effect was attenuated by volume but persisted for bladder and prostate surgery.

The Association Between Duration of Antibiotics and Infectious Complications Following Radical Cystectomy: Analysis of the 2019-2021 NSQIP Database.

OBJECTIVES: To identify the impact of the duration of peri-operative antibiotics on infectious complications following radical cystectomy. METHODS: The National Surgical Quality Improvement Project (NSQIP) targeted database was queried for patients undergoing radical cystectomy from 2019 to 2021. Baseline patient characteristics were collected. Antibiotic duration was classified as <24 hours (short), 24-72 hours (intermediate) or >72 hours (long). Infectious complication data were collected including surgical site infection (SSI), urinary tract infection (UTI), organ space infection, pneumonia, sepsis, and clostridium difficile infection up to 30 days after surgery. Univariate and multivariable analyses were performed to compare duration of antibiotic therapy to infectious outcomes. RESULTS: Of the 4363 patients who underwent radical cystectomy, 3250 (74%), 827 (19%) and 286 (6.6%) received short, intermediate, and long duration of peri-operative antibiotics, respectively. Infectious complication occurred in 954 (22%) patients, including 227 (5.2%) SSI, 280 (6.4%) UTI, 268(6.1%) organ space infection, 87 (2%) pneumonia, and 378 (8.7%) sepsis. Clostridium difficile infection occurred in 89 (2%) patients. On multivariable analysis, there was no significant difference in overall infectious complication rates with long-duration antibiotics. However, intermediate duration of antibiotics in open surgery was associated with a decreased risk of SSI (OR 0.58; 95%CI 0.37-0.91) compared to those treated with short-term antibiotics. CONCLUSION: Despite guideline recommendations, 26% of patients in this database received >24 hours of peri-operative antibiotics without decreased risk of overall infectious complication. An intermediate course of antibiotics decreased risk of SSI in open surgery compared to the guideline recommend <24-hour course. Greater education regarding antibiotic stewardship and further studies investigating infectious complications are warranted.

Comparing the rate of immunotherapy treatment change due to toxicity by sex.

BACKGROUND: Immuno-oncology therapy (IO) is associated with a variety of treatment-related toxicities. However, the impact of toxicity on the treatment discontinuation rate between males and females is unknown. We hypothesized that immune-related adverse events would lead to more frequent treatment changes in females since autoimmune diseases occur more frequently in females. AIMS: Our aim was to determine if there was a difference in the rate of immunotherapy treatment change due to toxicity between males and females. METHODS AND RESULTS: The Oncology Research Information Exchange Network Avatar Database collected clinical data from 10 United States cancer centers. Of 1035 patients receiving IO, 447 were analyzed, excluding those who did not have documentation noting if a patient changed treatment (n = 573). Fifteen patients with unknown or gender-specific cancer were excluded. All cancer types and stages were included. The primary endpoint was documented treatment change due to toxicity. Four hundred and forty-seven patients (281 males and 166 females) received IO treatment. The most common cancers treated were kidney, skin, and lung for 99, 84, and 54 patients, respectively. Females had a shorter IO course than males (median 3.7 vs. 5.1 months, respectively, p = .02). Fifty-four patients changed treatment due to toxicity. There was no significant difference between females and males on chi-square test (11.4% vs. 12.5%, respectively, p = 0.75) and multivariable logistic regression (OR 0.924, 95% CI 0.453-1.885, p = .827). Significantly more patients with chronic obstructive pulmonary disease (COPD) changed therapy due to toxicity (OR 2.491, 95% CI 1.025-6.054, p = .044). CONCLUSION: Females received a shorter course of IO than males. However, there was no significant difference in the treatment discontinuation rate due to toxicity between males and females receiving IO. Toxicity-related treatment change was associated with COPD.

Pelvic lymphadenectomy: Evaluating nodal stage migration and will rogers effect in bladder cancer.

INTRODUCTION: Pelvic lymphadenectomy (PLND) alongside radical cystectomy (RC), provides crucial diagnostic and therapeutic value in patients with bladder cancer. With the advent of neoadjuvant chemotherapy and prospective data supporting standard PLND, controversy remains regarding the optimal PLND extent and patient selection. Nearly 40% of patients may not receive adequate PLND, even though 25% of patients have positive lymph nodes (LN) at time of RC. We hypothesized that PLND still remains an important facet of bladder cancer treatment. To clarify the prognostic importance of nodal yield, we performed a retrospective investigation of a heterogenous population (pTanyNx/0M0) of patients undergoing RC. METHODS: From the Surveillance, Epidemiology, and End Results (SEER) program, we identified pTanyNx/0M0 bladder cancer patients undergoing RC from 2004 to 2015. Kaplan Meier curves and Cox proportional hazards models assessed cancer-specific survival. Patients were analyzed with PLND performed as the primary covariate. Survival analysis then stratified patients undergoing PLND by LN yield, both as a continuous and categorial variable (≤10, 11-20, 21-30, and >30), and T stage. RESULTS: The final cohort included pTanyNx/0M0 patients with urothelial bladder cancer (n = 12,096); median follow up was 39 (IQR: 17-77) months. PLND was performed in 81.45% of patients with a median LN yield of 14 (IQR: 7-23). Most commonly, patients had T2 disease (44.68%). After controlling for age and T stage, patients receiving PLND had improved CSS (HR = 0.56, [95% CI: 0.51-0.62]) compared to those that did not receive PLND. When grouping patients by LN yield, survival improved in a "dose dependent" manner (>30 LN: HR = 0.76, [95% CI: 0.66-0.87]). We noted similar results when stratifying patients into non-muscle-invasive (NMIBC) and muscle-invasive bladder cancer (MIBC). CONCLUSIONS: In a large contemporary series of pTanyNx/0M0 bladder cancer patients, we found a significant oncologic benefit to PLND. Higher LN yield correlated to improved CSS in non-muscle-invasive and muscle-invasive disease. Our data support the possibility of occult micrometastasis even in non-muscle-invasive disease. Additionally, in light of recent advances in adjuvant immunotherapy, our results emphasize the importance of adequate nodal yield for accurate staging and optimal treatment.

Chromophobe Renal Cell Carcinoma with Sarcomatoid Differentiation.

Chromophobe renal cell carcinoma (chRCC) is one of the less common types of kidney cancer and generally portends a more favorable prognosis. RCC with sarcomatoid differentiation has a more aggressive clinical course with poor outcomes. Four cases of chRCC with varying degrees of sarcomatoid differentiation were retrospectively reviewed at our institution, and clinicopathologic data as well as clinical courses were reported. Patients with higher degrees of sarcomatoid differentiation and larger tumors at presentation generally had and worse overall survival. chRCC with sarcomatoid differentiation portends a poor prognosis with limited data on systemic treatment options for metastatic disease.

A Restaging Transurethral Resection of Bladder Tumor Is Always Necessary For High-grade T1 Non-muscle-invasive Bladder Cancer.

Patients with high-grade T1 non-muscle-invasive bladder cancer (NMIBC) have a high risk of recurrence and upstaging. Restaging transurethral resection of bladder tumor allows better staging so that patients can proceed to the appropriate treatment in a timely manner. This should be done in all patients with high-grade T1 NMIBC.

Survey of Informed Consent Procedures in Urology: Disclosing Resident Participation to Patients.

AbstractThe American Urological Association (AUA) and American College of Surgeons (ACS) codes of professionalism require surgeons to disclose the specific roles and responsibilities of trainees to patients during the informed consent process. The objective of this study is to analyze how these requirements are met by urology training programs. An anonymous electronic survey was distributed to the program directors (PDs) of the 143 Accreditation Council for Graduate Medical Education urology residency programs in the United States in 2021. Information was collected regarding program demographics, aspects of the program's consent process, and the disclosure to patients of the role and participation of residents in their surgery. There were 49 responses to the survey (34.3% response rate). Nearly 70 percent of PDs reported that attending physicians lead the consent process. The topics covered during consent discussion include possible complications (25%), expected recovery time (23%), length of the surgery (22%), the people involved (18%), and their specific roles (7%). Many PDs do not explicitly discuss trainee involvement (48.8%) or when a resident is to perform the majority of the case (87.8%). The majority of PDs (78.8%) communicate medical student involvement, but 73.2 percent reported having a patient decline participation of a trainee after describing their role. Despite the AUA and ACS codes of professionalism, many urologists do not disclose resident involvement in surgery to patients. Further discussions are needed to explore how to better balance resident education and patient autonomy.

Annual trends of cystectomy complications: A contemporary analysis of the NSQIP database.

INTRODUCTION: Despite significant morbidity, radical cystectomy (RC) is standard of care for muscle invasive bladder cancer, certain high-risk nonmuscle invasive tumors and after failure of intravesical or trimodal therapy. Modern efforts have hastened the recovery after this surgery without impact on overall complication rates. Our primary aim was to examine changes in complication rates of RC over time. METHODS: The National Surgical Quality Improvement Program database included 11,351 RC from 2006 to 2018 for nondisseminated bladder cancer. Baseline characteristics and complication rates were studied across time periods: 2006 to 2011, 2012 to 2014, and 2015 to 2018. Thirty-day complications, readmissions, and mortality were identified. RESULTS: Overall complication rates decreased over time (56.5%, 57.4%, 50.6%, P < 0.01). Infectious complications were stable, including UTIs (10.1%, 8.8%, 8.3% respectively, P = 0.11) and sepsis (10.4%, 8.8%, 8.7% respectively, P = 0.20). On multivariable analysis, ASA≥3 (OR 1.399, 95% CI 1.279-1.530) was associated with increased complications, while procedures in 2015 to 2018 (OR 0.825, 95% CI 0.722-0.942), laparoscopic/robotic approach (OR 0.555, 95%CI 0.494-0.622), and ileal conduit (OR 0.796, 95% CI 0.719-0.882) were associated with decreased complication rates. Other outcomes of interest included mean length of stay (LOS), which decreased over time (10.5, 9.8, 8.6 days, respectively, P < 0.01) and readmission (20.0%, 21.3%, 21.0%, respectively, P = 0.84) and mortality rates were stable (2.7%, 1.7%, 2.0%, respectively, P = 0.13). CONCLUSION: Decreased early complications and LOS after RC over time may reflect beneficial effects of recent advances in bladder cancer treatment such as enhanced recovery after surgery protocols and minimally invasive techniques. Further opportunities to improve long term outcomes, readmissions and infection rates are needed.

Factors associated with clinical trial participation for patients with renal cell carcinoma.

OBJECTIVE: Recruitment of a diverse and representative study population is critical to the external validity of oncology clinical trials. The primary objective of this study was to characterize the factors associated with clinical trial participation for patients with renal cell carcinoma and the secondary objective was to examine differences in survival outcomes. MATERIALS AND METHODS: We used a matched case-control design by querying the National Cancer Database for patients with renal cell carcinoma who were coded as having enrolled in a clinical trial. Trial patients were matched in a 1:5 ratio to the control cohort based on clinical stage and then sociodemographic variables were compared between the 2 groups. Multivariable conditional logistic regression models evaluated factors associated with clinical trial participation. The trial patient cohort was then matched again in a 1:10 ratio based on age, clinical stage, and comorbidities. Log-rank test was used to compare overall survival (OS) between these groups. RESULTS: From 2004 to 2014, 681 patients enrolled in clinical trials were identified. Clinical trial patients were significantly younger and had a lower Charlson-Deyo comorbidity score. On multivariate analysis, male patients and white patients were more likely to participate compared to their Black counterparts. Having Medicaid or Medicare negatively associated with trial participation. Median OS was greater among clinical trial participants. CONCLUSION: Patient sociodemographic factors remain significantly associated with clinical trial participation and trial participants experienced superior OS to their matched counterparts.

Wound Complication Rates after Inguinal Lymph Node Dissection: Contemporary Analysis of the NSQIP Database.

BACKGROUND: Inguinal lymph node dissection (ILND) is used for diagnosis and treatment in penile cancer (PC), vulvar cancer (VC), and melanomas draining to the inguinal lymph nodes. However, ILND is often characterized by its morbidity and high wound complication rate. Consequently, we aimed to characterize wound complication rates after ILND. STUDY DESIGN: The NSQIP database was queried for ILND performed from 2005 to 2018 for melanoma, PC, or VC. Thirty-day wound complications included wound disruption and superficial, deep, and organ-space surgical site infection. Multivariable logistic regression was performed with covariates, including cancer type, age, American Society of Anesthesiologists score ≥3, BMI ≥30, smoking history, diabetes, operative time, and concomitant pelvic lymph node dissection. RESULTS: A total of 1,099 patients had an ILND with 92, 115, and 892 ILNDs performed for PC, VC, and melanoma, respectively. Wound complications occurred in 161 (14.6%) patients, including 12 (13.0%), 17(14.8%), and 132 (14.8%) patients with PC, VC, and melanoma, respectively. Median length of stay was 1 day (interquartile range 0 to 3 days), and median operative time was 152 minutes (interquartile 83 to 192 minutes). Readmission rate was 12.7%. Wound complications were associated with longer operative time per 10 minutes (odds ratio 1.038, 95% CI 1.019 to 1.056, p < 0.001), BMI ≥30 (odds ratio 1.976, 95% CI 1.386 to 2.818, p < 0.001), and concomitant pelvic lymph node dissection (odds ratio 1.561, 95% CI 1.056 to 2.306, p = 0.025). CONCLUSIONS: Predictors of wound complications after ILND include BMI ≥30, longer operative time, and concomitant pelvic lymph node dissection. There have been efforts to decrease ILND complication rates, including minimally invasive techniques and modified templates, which are not captured by NSQIP, and such approaches may be considered especially for those with increased complication risks.