Effect of a variant histology on the oncological outcomes of Japanese patients with upper tract urothelial carcinomas after radical nephroureterectomy: a multicenter retrospective study.

Background: An earlier systematic review and meta-analysis found that patients with a certain histological variant of upper tract urothelial carcinoma (UTUC) exhibited more advanced disease and poorer survival than those with pure UTUC. A difference in the clinicopathological UTUC characteristics of Caucasian and Japanese patients has been reported, but few studies have investigated the clinical impact of the variant histology in Japanese UTUC patients. Methods: We retrospectively enrolled 824 Japanese patients with pTa-4N0-1M0 UTUCs who underwent radical nephroureterectomy without neoadjuvant chemotherapy. Subsequently, we explored the effects of the variant histology on disease aggressiveness and the oncological outcomes. We used Cox's proportional hazards models to identify significant predictors of oncological outcomes, specifically intravesical recurrence-free survival (IVRFS), recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Results: Of the 824 UTUC patients, 32 (3.9%) exhibited a variant histology that correlated significantly with a higher pathological T stage and lymphovascular invasion (LVI). Univariate analysis revealed that the variant histology was an independent risk factor for suboptimal RFS, CSS, and OS. However, significance was lost on multivariate analyses. Conclusions: The variant histology does not add to the prognostic information imparted by the pathological findings after radical nephroureterectomy, particularly in Japanese UTUC patients.

Real-world outcomes of adjuvant immunotherapy candidates with upper tract urothelial carcinoma: results of a multicenter cohort study.

BACKGROUND: Recent clinical trials have reported improved disease-free survival rates of patients with stage pT3-4/ypT2-4 or pN + upper tract urothelial carcinoma (UTUC) on adjuvant nivolumab therapy. However, the appropriateness of the patient selection criteria used in clinical practice remains uncertain. METHODS: We retrospectively analyzed 895 patients who underwent nephroureterectomy to treat UTUC. The patients were divided into two groups: grade pT3-4 and/or pN + without neoadjuvant chemotherapy (NAC) or grade ypT2-4 and/or ypN + on NAC (adjuvant immunotherapy candidates) and others (not candidates for adjuvant immunotherapy). Kaplan-Meier curves were drawn to assess the oncological outcomes, including recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Cox proportional hazards models were used to identify significant prognostic factors for oncological outcomes. RESULTS: The Kaplan-Meier curves revealed notably inferior RFS, CSS, and OS of patients who were candidates for adjuvant immunotherapy. Multivariate analysis revealed that pathological T and N grade and lymphovascular invasion (LVI) status were independent risk factors for poor RFS, CSS, and OS. CONCLUSION: In total, 44.8% of patients were candidates for adjuvant immunotherapy. In addition to pathological T and N status, LVI was a significant predictor of survival, and may thus play a pivotal role in the selection of patients eligible for adjuvant immunotherapy.

Comparison of neoadjuvant and adjuvant chemotherapy for upper tract urothelial carcinoma in real-world practice: a multicenter retrospective study.

BACKGROUND: Multiple studies have demonstrated the effectiveness of neoadjuvant chemotherapy and adjuvant chemotherapy in patients with upper tract urothelial carcinoma compared with surgery alone. However, no clinical trial has established the superiority of neoadjuvant chemotherapy or adjuvant chemotherapy in terms of perioperative outcomes. METHODS: We conducted a retrospective analysis encompassing 164 upper tract urothelial carcinoma patients who underwent radical nephroureterectomy and received perioperative chemotherapy. Of these patients, 65 (39.6%) and 99 (60.4%) received neoadjuvant chemotherapy and adjuvant chemotherapy, respectively. Recurrence-free survival and cancer-specific survival were computed using the Kaplan-Meier method. Additionally, we conducted Cox regression analyses to evaluate the risk factors for recurrence-free survival and cancer-specific survival. RESULTS: Pathological downstaging was seen in 37% of the neoadjuvant chemotherapy group. However, no pathological complete response was observed in this cohort. The Kaplan-Meier curves demonstrated significantly lower recurrence-free survival and cancer-specific survival in patients who received adjuvant chemotherapy. Multivariate Cox regression analysis revealed patients treated with adjuvant chemotherapy exhibited a marked association with inferior recurrence-free survival and cancer-specific survival. CONCLUSION: Our study has suggested that neoadjuvant chemotherapy would be more effective in high-risk upper tract urothelial carcinoma patients compared with adjuvant chemotherapy.

Does castration status affect docetaxel-related adverse events? :Identification of risk factors for docetaxel-related adverse events in metastatic prostate cancer.

BACKGROUND: Docetaxel-related adverse events (AEs) such as neutropenia and febrile neutropenia (FN) can be life-threatening. A previous in vivo study raised the hypothesis that the castration status affects the rate of hematologic AEs. We aimed to investigate the impact of castration status on the incidence of docetaxel-related AE in metastatic prostate cancer (mPCa) patients. METHODS: We retrospectively analyzed the records of 265 mPCa patients treated with docetaxel, comprising 92 patients with metastatic hormone-sensitive prostate cancer (mHSPC) and 173 patients with metastatic castration-resistant prostate cancer (mCRPC) between January 2015 and December 2021. Common terminology Criteria for Adverse Events (CTCAE) was applied to evaluate AEs. We analyzed the differential incidences between mHSPC and mCRPC, and risk factors of hematologic and nonhematologic AEs using a logistic regression model. RESULTS: The rate of patients who received primary prophylaxis against neutropenia was higher in those with the mHSPC compared with those with the mCRPC (7.5% vs. 33%, p < 0.001). Among the patients without primary prophylaxis, incidence rates of severe neutropenia (CTCAE ≥ Grade3) and FN were 89% and 16% in patients with mCRPC compared to 81% and 18% in those with mHSPC. Logistic regression analysis revealed that age ≥ 75 years and failure to provide primary prophylaxis were independent risk factors of severe neutropenia (odds ratio [OR]: 2.39, 95% confidential interval [CI]: 1.10-5.18 and OR: 15.8, 95% CI: 7.23-34.6, respectively). Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≧ 1 was an independent risk factor of FN (OR: 2.26, 95% CI: 1.13-4.54). Castration status (mHSPC vs. mCRPC) was not associated with the risks of severe neutropenia and FN. CONCLUSIONS: Castration status did not affect the risk of severe neutropenia or FN in mPCa patients treated with docetaxel regardless of the disease state. Failure to provide primary prophylaxis and advanced patient age are independent risk factors of severe neutropenia; while patients with poor PS are more likely to develop FN. These findings may help guide the clinical decision-making for proper candidate selection of docetaxel treatment.