An in-depth analysis on the effects of body composition in patients receiving neoadjuvant chemotherapy for urothelial cell carcinoma.

INTRODUCTION: Neoadjuvant chemotherapy (NAC) is the standard of care for patients undergoing radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC); however, NAC can be associated with significant side effects and morbidity in some patients. NAC may contribute to sarcopenia, obesity, and the combination of the two. Our study examined the effects of NAC on body composition and the association between body composition and adverse events. METHODS: We created a retrospective database of patients with non-metastatic MIBC receiving NAC prior to RC. The change in skeletal muscle index (SMI) and fat mass index (FMI) was calculated using computed tomography (CT) scans done within three months prior to NAC and after the first two cycles. The association between body composition (sarcopenia, obesity, and sarcopenic obesity) and preoperative adverse events was investigated using a multivariable logistic regression. Changes in body composition were calculated using a paired Student's t-test. RESULTS: A total of 70 patients were included in our study. There was a mean decrease in SMI of 2.2±3.2 cm2/m2. Adiposity and FMI were unchanged by NAC. Sarcopenic obesity was found to be associated with adverse events among patients receiving NAC in the multivariable analysis. There was a total of 637 preoperative complications with grades 1-2 and 33 complications with grades 3-5. CONCLUSIONS: Based on our retrospective cohort study, NAC did not affect obesity and FMI, but there was a significant decrease in SMI. Sarcopenic obesity was associated with increased severity of NAC adverse events. As such, the presence of this factor may help predict tolerance of NAC.

Perioperative systemic therapy in renal cell carcinoma.

PURPOSE OF REVIEW: Renal cell carcinoma (RCC) is the most common kidney neoplasm. Localized RCC can be cured with nephrectomy. However, a proportion of patients will recur with incurable distant metastatic disease. There is a clear need for treatments to reduce the risk of RCC recurrence and thus improve survival. This review describes the landscape of perioperative therapy for RCC, focusing on more recent trials involving immune checkpoint inhibitors (ICIs). RECENT FINDINGS: ICIs have significantly changed outcomes in advanced RCC. Four trials investigating the role of perioperative ICI for RCC are now reported. Only one trial utilizing adjuvant pembrolizumab (Keynote-564) has shown a disease-free survival benefit in resected RCC. SUMMARY: Patients with resected RCC should be counselled on their risk of recurrence and the potential option of adjuvant pembrolizumab, recognizing that overall survival data are not yet available.

Utilization and Safety of Ipilimumab Plus Nivolumab in a Real-World Cohort of Metastatic Renal Cell Carcinoma Patients.

INTRODUCTION: Ipilimumab plus nivolumab was associated with a survival benefit in a phase III clinical trial of first-line treatment for metastatic renal cell carcinoma (mRCC). In this study, mRCC patients from the Canadian Kidney Cancer Information System (CKCis) database who received first-line ipilimumab plus nivolumab were analyzed to determine the safety and outcomes in a real-world setting. PATIENTS AND METHODS: Patients who received ipilimumab plus nivolumab as first-line therapy for mRCC in CKCis, were identified, and the amount of treatment received, discontinuation rates, and reasons for discontinuing treatment were determined. Toxicity data, including type and grade, were collected. Efficacy outcomes of interest included overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). RESULTS: The cohort included 195 patients, the majority with clear cell histology (74%). All 4 cycles of ipilimumab plus nivolumab were administered in 124 patients (64%). Progressive disease (n = 87; 45%) and toxicity (n = 36; 18%) were the most common causes for discontinuing treatment. Several patients (n = 18) did not receive all 4 doses of ipilimumab but received single agent nivolumab. The estimated median OS was 54.5 months (95% CI, 17.7 - NE) and 12-month OS was 72.2% (95% CI, 65.0 - 79.3). Median PFS was 7.4 months (95% CI 5.3 - 10.2) and ORR was 42.5%. Patients who received all 4 cycles of ipilimumab plus nivolumab had better ORR (50% vs. 28%) and a longer PFS and OS than those who received less than 4 cycles (P < .0001). Ninety-five AEs were documented in 72 patients who required dose reduction/change, with colitis being the most frequent. CONCLUSION: In this real-world cohort of treatment-naïve mRCC patients, outcomes, and safety were comparable to previously reported clinical trial data.

What Do International Guidelines Say About First-line Therapy for Clear-cell Metastatic Renal Cell Carcinoma?

Treatment options for clear-cell metastatic renal cell carcinoma (mRCC) have increased significantly. Clinical practice guidelines aim to aid with decision-making about treatment selection through evidence-based recommendations. In this article, recommendations on first-line treatment for clear-cell mRCC in guidelines from three international organizations are reviewed and summarized. Future guideline development should focus on dynamic updates based on practice-changing data and guidance regarding therapy selection. PATIENT SUMMARY: International guidelines for first-line treatment of metastatic renal cell carcinoma are reviewed in this article. The main differences between guidelines appear to be how quickly the newest evidence is included.

Rare case of upper urinary tract squamous cell carcinoma presenting with significant paraneoplastic syndrome.

Squamous cell carcinoma of the upper urinary tract is a rare entity associated with rapidly progressive disease and poor outcomes. Here, we describe a case of a squamous cell carcinoma of the upper urinary tract associated with significant progression and paraneoplastic syndrome. Post-operatively, the patient had near complete resolution of her paraneoplastic syndromes with significant improvements in her functional status.