A collaborative review of the microsatellite instability/deficient mismatch repair phenotype in patients with upper tract urothelial carcinoma.

OBJECTIVE: To perform a collaborative review of the literature exploring the microsatellite instability/deficient mismatch repair (MSI/dMMR) phenotype in patients with upper tract urothelial carcinoma (UTUC). METHOD: A collaborative review of the literature available on Medline was conducted by the Cancer Committee of the French Association of Urology to report studies describing the genetic mechanisms, investigation, prevalence and impact of the MSI/dMMR phenotype in UTUC patients. RESULTS: The predominant genetic mechanism leading to the MSI/dMMR phenotype in UTUC patients is related to the constitutional mutation of one allele of the MMR genes MLH1, MSH2, MSH6 and PMS2 within Lynch syndrome. Indications for its investigation currently remain limited to patients with a clinical suspicion for sporadic UTUC to refer only those with a positive testing for germline DNA sequencing to screen for this syndrome. With regard to technical aspects, despite the interest of MSIsensor, only PCR and immunohistochemistry are routinely used to somatically investigate the MSI and dMMR phenotypes, respectively. The prevalence of the MSI/dMMR phenotype in UTUC patients ranges from 1.7% to 57%, depending on the study population, investigation method and definition of a positive test. Younger age and a more balanced male to female ratio at initial diagnosis are the main specific clinical characteristics of UTUC patients with an MSI/dMMR phenotype. Despite the conflicting results available in the literature, these patients may have a better prognosis, potentially related to more favourable pathological features. Finally, they may also have lower sensitivity to chemotherapy but greater sensitivity to immunotherapy. CONCLUSION: Our collaborative review summarises the available data from published studies exploring the MSI/dMMR phenotype in UTUC patients, the majority of which are limited by a low level of evidence.

Efficacy and tolerance of hyperthermic intravesical chemotherapy (HIVEC) according to the number of instillations administered.

PURPOSE: To report the oncological outcomes and the tolerance between 6 instillations and more than 6 cycles of hyperthermic intravesical chemotherapy(HIVEC) in patients with non-muscle invasive bladder cancer(NMIBC). METHODS: This is a multicenter retrospective study from a national database including 9 expert centers. All patients treated with HIVEC between 2016 and 2023 for NMIBC were included. Patients were classified into two groups according to the total number of HIVEC instillations, including induction plus maintenance. Kaplan-Meier curves were computed to present survival outcomes. RESULTS: 261 patients with a median follow-up of 25.5 months were included. 199(76.2%) and 62(23.8%) were treated by 6 and more than 6 cycles of HIVEC, respectively. The 2-years RFS(40.2% vs. 34.4%,p = 0.3) and the 2-years PFS(86% vs. 87%,p = 0.85) were similar between group treated with 6 and more than 6 instillations. 2-years CSS and OS were also similar between both groups. Univariate Cox regression showed no association between the number of bladder instillation and RFS (HR = 1.2 95%CI[0.8-1.84], p = 0.3) or PFS (HR = 0.8 95%CI[0.29-2.02], p = 0.2). In the group treated with more than 6 cycles, 2-years RFS and 2-years PFS were similar between patients who received induction plus maintenance compared to those treated with induction only. Finally, hematuria and urinary burning were significantly higher in the group treated by more than 6 cycles (21% vs. 8.5%(p < 0.01),and 29% vs. 17% (p = 0.03), respectively). Serious side effects(grade ≥ 3) are rare(3.1%) and similar in both groups. CONCLUSIONS: Results show no significant difference in two years RFS, PFS, CSS and OS according to number of instillations received, while toxicity profile seems better in the group receiving six instillations only.

Perioperative, renal function and oncological outcomes of robot-assisted radical nephroureterectomy for patients with upper tract urothelial carcinoma.

PURPOSE: To report perioperative, renal function and oncological outcomes of robot-assisted radical nephroureterectomy (RNU) for patients with upper tract urothelial carcinoma (UTUC). METHODS: This was a retrospective single-arm monocentric study including all consecutive UTUC patients treated with robot-assisted RNU at our institution between 2014 and 2022. Descriptive statistics with median and interquartile range (IQR) for continuous variables and numbers with frequencies for categorical variables were used to report perioperative and renal function outcomes while Kaplan-Meier curves were computed to present extravesical and intravesical recurrence-free survival(RFS) as well as cancer-specific (CSS) and overall survival (OS) with the corresponding 95% confidence intervals(CIs). RESULTS: Overall, 70 patients with a median age of 69.6 [63.3-74.9] years were included in our study. With regards to perioperative outcomes, the median operative time was 157 [130-182] min with a median blood loss of 200 [100-300] cc. Intraoperative complications occurred in 4 (5.7%) patients but no conversion to open or laparoscopic surgery was required. Postoperative complications occurred in 9 (12.9%) patients, including 5 (7.1%) with grade ≥ 3 complications according to the Clavien-Dindo classification. The median length of stay was 4 [3-6] days. With regards to renal function outcomes, the median postoperative loss in estimated glomerular filtration rate at discharge was 16 [10.25-26] mL/min/1.73 m2. With regards to oncological outcomes, the 3-year extravesical and intravesical RFS, CSS and OS rates were 73.6 [62.8-86.2]%, 68.1 [54.6-85]%, 82.5 [72-94.4]% and 75.3 [63.4-89.5]%, respectively. CONCLUSION: We report favorable perioperative and oncological outcomes with expected decrease in renal function after robot-assisted RNU for patients with UTUC.