Bajorin DF, Witjes JA, Gschwend JE et al: Adjuvant nivolumab versus placebo in muscle-invasive urothelial carcinoma. N Engl J Med 2021; 384: 2102–2114.

While neo-adjuvant treatment is standard for high-risk bladder cancer amenable to cystectomy, the impact of adjuvant therapy is less clear. In this multicenter study, patients with muscle-invasive urothelial carcinoma who had undergone radical surgery were randomized to receive either nivolumab (240 mg intravenously) or placebo every 2 weeks for up to 1 year.

Neoadjuvant cisplatin-based chemotherapy before trial entry was allowed. The primary end points were disease-free survival among all the patients (intention-to-treat population) and among patients with a tumor programmed death ligand 1 (PD-L1) expression level of 1% or more. A total of 353 patients were assigned to receive nivolumab and 356 to receive placebo. The median disease-free survival in the intention-to-treat population was 20.8 months (95% CI 16.5–27.6) with nivolumab and 10.8 months (95% CI 8.3–13.9) with placebo. The percentage of patients who were alive and disease-free at 6 months was 74.9% with nivolumab and 60.3% with placebo (HR for disease recurrence or death 0.70, 98.22% CI 0.55–0.90, p <0.001). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 74.5% and 55.7%, respectively (HR 0.55, 98.72% CI 0.35–0.85, p <0.001). The median survival free from recurrence outside the urothelial tract in the intention-to-treat population was 22.9 months (95% CI 19.2–33.4) with nivolumab and 13.7 months (95% CI 8.4–20.3) with placebo. The percentage of patients who were alive and free from recurrence outside the urothelial tract at 6 months was 77.0% with nivolumab and 62.7% with placebo (HR for recurrence outside the urothelial tract or death 0.72, 95% CI 0.59–0.89). Among patients with a PD-L1 expression level of 1% or more, the percentage of patients was 75.3% and 56.7%, respectively (HR 0.55; 95% CI 0.39–0.79). Treatment-related adverse events of grade 3 or higher occurred in 17.9% of the nivolumab group and 7.2% of the placebo group. Two treatment-related deaths due to pneumonitis were noted in the nivolumab group.

The authors conclude that disease-free survival was longer with adjuvant nivolumab than with placebo in the intention-to-treat population and among patients with a PD-L1 expression level of 1% or more.

Khaleel S, Regmi S, Hannah P et al: Impact of preoperative immunonutrition on perioperative outcomes following cystectomy. J Urol 2021; doi: 10.1097/JU.0000000000001945.

Cystectomy remains one of the most morbid operations in urology, and there are many opportunities to prehab a patient to improve outcomes. Nutritional supplementation is one approach. In this paper, the authors performed a retrospective review of 204 patients who underwent cystecomy for bladder cancer at a single institution, comparing patients who received oral L-arginine-based preoperative immunonutrition (Pre-INS) with those who did not. Outcomes of interest included development of high-grade (Clavien-Dindo III–V) complications, readmission within 30 days, ileus, total parenteral nutrition (TPN) requirement, postoperative infection and length of stay (LOS). Patients who received Pre-INS had significantly lower odds of requiring postoperative TPN (17.3% vs 35.6%; Fisher p=0.015; OR=0.38) and developing postoperative infection (25% vs 45%; Fisher p=0.003; OR=0.41) but no significant difference in the rates of other outcomes. On multivariable regression, when adjusting for age, gender, body mass index, Charlson Comorbidity Index, undergoing neoadjuvant chemotherapy and operative features, Pre-INS was a significant predictor of postoperative infection (Fisher p=0.02; OR=0.35) but not for high-grade complications, readmission, ileus, needing TPN or LOS.

The authors conclude that preoperative immunonutrition with an L-arginine-based supplement is associated with significant reduction in postoperative infection, one of the most common complications of radical cystectomy.

Koo K, Javier-DesLoges JF, Fang R et al: Professional burnout, career choice regret, and unmet needs for well-being among urology residents. Urology 2021; doi: 10.1016/j.urology.2021.05.064.

Identifying urologist burnout is an important step to reform, and the AUA Census now includes questions regarding burnout and career decisional regret. In this study the authors performed a cross-sectional study describing U.S. urology residents’ responses to the 22-item Maslach Burnout Inventory and questions about career and specialty choice regret from the 2019 AUA Census. Respondents reported and prioritized unmet needs for resident well-being. Among 415 respondents (31% response), the prevalence of professional burnout was 47%. Burnout symptoms were significantly higher among second-year residents (65%) compared to other training levels (p=0.02); 17% and 9% of respondents reported regretting their overall career and specialty choices, respectively. Among the 53% of respondents who had ever reconsidered career and specialty choice, a majority (54%) experienced this most frequently during the second year of residency, significantly more than other training levels (p=0.04). Regarding unmet needs, 62% of respondents prioritized the ability to attend personal health appointments; the majority experienced difficulty attending such appointments during work hours, more so among women than men (70% vs 53%, p <0.01).

The authors conclude that targeting interventions to early-career residents and enabling access to medical and mental health care should be priorities for reform.

While we all can agree that evidence-based treatments for burnout can be helpful for those experiencing it, true priorities for reform will need to address the underlying causes and not put the blame on the inadequate personal resources of the physician to respond to them.