Avelumab in metastatic collecting duct carcinoma of the kidney: a case report.

BACKGROUND: Collecting duct carcinoma (CDC) of the kidney is associated with an aggressive course, limited response to treatment, and poor prognosis. Platinum-based chemotherapy is currently recommended as the first-line treatment in patients with metastatic CDC. Accumulating evidence supports the use of immunotherapy with checkpoint inhibitors as second-line therapy. CASE PRESENTATION: In this case report, we describe the first case of avelumab administration due to disease progression during chemotherapy with gemcitabine and cisplatin in a Caucasian, 71-year-old man presenting with multiple metastases due to CDC of the kidney. The patient initially responded well to four cycles of chemotherapy and his performance status improved. After two additional chemotherapy cycles, the patient presented with new bone and liver metastases (mixed response to chemotherapy with an overall 6-month progression-free survival). We offered him avelumab as a second-line treatment in this setting. The patient received a total of three cycles of avelumab. The disease remained stable (no new metastases during treatment with avelumab), and the patient developed no complications. To alleviate his symptoms, radiation therapy for the bone metastases was decided. Despite successful radiation of the bone lesions and further improvement of symptoms, the patient developed hospital-acquired pneumonia and died approximately ten months after the initial diagnosis of CDC. CONCLUSIONS: Our findings suggest that the applied treatment modality with gemcitabine and cisplatin chemotherapy followed by avelumab was effective in terms of both progression-free survival and quality of life. Still, further studies assessing the use of avelumab in this setting are mandatory.

The Short- and Long-Term Effect of Radical Cystectomy in Frail Patients With Bladder Cancer.

BACKGROUND: Studies about perioperative complications and all-cause mortality in frail patients requiring radical cystectomy (RC) are scarce. We aimed to assess the short- and long-term effect of RC in frail patients with bladder cancer. PATIENTS AND METHODS: We performed a retrospective, cohort study including patients who underwent open RC due to bladder cancer from November 2013 to June 2022. Patients were considered frail when they fulfilled one of the following criteria: i) age ≥ 75 years; ii) Charlson Comorbidity Index ≥ 9; iii) American Society of Anesthesiologists classification ≥ 4; or iv) Clinical Frailty Scale score ≥ 5. We evaluated all-cause mortality and complications in frail versus nonfrail patients. The effect of urinary diversion with ileal conduit versus ureterocutaneostomy in frail patients was also assessed via a Cox regression analysis. RESULTS: Overall, 184 individuals underwent RC (95 frail and 89 nonfrail). A total of 130 patients (80%) presented at least one perioperative complication. This proportion was even higher among frail patients (86%). Similarly, severe perioperative complications were more common in frail patients based on the Clavien-Dindo classification (P = 0.044). Regarding disease progression and long-term complications, no statistically significant differences were observed between frail and nonfrail patients. The survival analysis with Kaplan-Meier curves demonstrated that the risk of death was increased in frail patients (log-rank test = 0.027). Based on the multivariate Cox regression analysis adjusting for major risk factors, urinary diversion with ureterocutaneostomy was significantly associated with increased mortality in frail patients compared to ileal conduit (Hazard Ratio: 3.5, 95% Confidence Interval: 1.3-9.4, P = 0.01). CONCLUSIONS: RC is feasible in frail patients but is associated with increased perioperative morbidity and mortality. Preoperative frailty screening should be implemented to counsel and carefully select patients eligible for RC.

The effect of urinary diversion on renal function after cystectomy for bladder cancer: comparison between ileal conduit, orthotopic ileal neobladder, and heterotopic ileocecal pouch.

PURPOSE: To explore the impact of ileal conduit (IC), orthotopic ileal neobladder, and MAINZ Pouch I on renal function (RF) over time. METHODS: We performed a retrospective, cohort study including consecutive patients who underwent open radical cystectomy due to bladder cancer from November 2013 to June 2022. RF deterioration was calculated based on the estimated glomerular filtration rate (eGFR) through the CKD-EPI creatinine equation. A linear mixed-effects model was constructed, adjusting for multiple risk factors. The probability of achieving an eGFR reduction greater than 25% compared to baseline among different urinary diversion techniques was assessed using a Kaplan-Meier curve. RESULTS: Overall, 107 patients received IC, 28 neobladder, and 20 MAINZ Pouch I. Those receiving IC were older and displayed more comorbidities. At follow-up, eGFR was lower by 0.09 mL/min/1.73m2 (confidence interval - 5.87 to 5.69, p = 0.975) in patients receiving neobladder compared to those receiving IC. Similarly, eGFR was higher by 4.64 mL/min/1.73m2 (confidence interval - 1.57 to 10.85, p = 0.143) in patients receiving pouch compared to those receiving IC. Accordingly, patients with higher preoperative eGFR (p < 0.001), lower age (p = 0.048), non-T4 histological tumor (p = 0.027) and absence of septicemia at follow-up (p = 0.002) presented higher eGFR values at follow-up. The three UD techniques did not differ significantly in the time-to-event analysis (log-rank test = 0.29). CONCLUSIONS: A substantial proportion of patients undergoing urinary diversion with IC, orthotopic ileal neobladder, or MAINZ Pouch I develop RF deterioration at follow-up. No significant differences were observed among the three UD techniques in terms of eGFR decline in the long-term.