Treatment outcome after sequential chemotherapy with cisplatin-etoposide, amrubicin and nogitecan in patients with treatment-related pure small-cell neuroendocrine prostate cancer.

OBJECTIVE: This study retrospectively reviewed the clinical characteristics and treatment outcomes of patients with histologically diagnosed treatment-related pure small-cell neuroendocrine prostate cancer. METHODS: We retrospectively evaluated data for 13 patients with treatment-related neuroendocrine prostate cancer who were diagnosed between May 2015 and February 2022. Standardized systemic therapies of etoposide plus cisplatin (or carboplatin), amrubicin and nogitecan were selected as sequential treatments. Cancer-specific survival and progression-free survival were evaluated as the primary endpoint. The Cox proportional hazards model was used to evaluate the relationships between treatment regimens, clinical variables, cancer-specific survival and progression-free survival. RESULTS: The median cancer-specific survival after diagnosis for all patients was 22.4 months (range 1.3-33.4 months). The median progression-free survival was 9.3 months after first-line etoposide plus cisplatin (or carboplatin) treatment (n = 13); 4.2 months after second-line amrubicin treatment (n = 4); and >15 months after third-line nogitecan treatment (n = 2). The median progression-free survival after first-line chemotherapy of the liver metastasis (-) group was 10.2 months, and that of the (+) group was 5.3 months (P = 0.015, hazard ratio = 11.6, 95% confidence interval = 1.01 - 133.7). No clinicopathological parameters were identified as significant independent predictors of cancer-specific survival in univariate analysis. CONCLUSION: Sequential chemotherapy with etoposide plus cisplatin (or carboplatin), amrubicin and nogitecan may be helpful for patients with treatment-related pure small-cell neuroendocrine prostate cancer. Early biopsy of metastases and initiation of effective therapy is essential for patients with progressive castration-resistant prostate cancer and low prostate-specific antigen.

Impact of adjuvant chemotherapy for patients with locally advanced upper tract urothelial carcinoma in real-world clinical practice.

INTRODUCTION: The impact of adjuvant chemotherapy (ACT) using regimens including gemcitabine and platinum on the improvement of the prognosis of patients with locally advanced upper tract urothelial carcinoma (UTUC) has been recently demonstrated. This study aimed to determine the utility of ACT for patients with locally advanced UTUC in real-world clinical practice and the differences in efficacy among regimens. METHODS: Of 206 UTUC patients who underwent radical nephroureterectomy, 78 were pathologically diagnosed as T3 or higher and/or had pathologically identified lymph node metastasis; 36 in the ACT group and 42 in the non-ACT group were evaluated for patient background, recurrence, and prognosis. In the ACT group, either cisplatin (GC group, 12 cases) or carboplatin (GCa group, 24 cases) was administered as the platinum agent to be combined with gemcitabine. RESULT: The median patient age in the ACT group and that in the non-ACT group was 71 and 79 years, respectively (p<0.0001). There was no significant difference between these two groups in terms of other patient parameters. The two- and five-year cancer-specific survival (CSS ) and the two- and five-year disease-free survival (DFS) for the ACT group were 81.7%, 66.0%, 60.6%, and 56.6%, respectively, and for the non-ACT group were 68.4%, 40.5%, 42.8%, and 29.3%, respectively (p=0.0399 for CSS and p=0.0814 for DFS). There was no significant difference in CSS and DFS between the GC group and GCa group (p=0.9846 and p=0.9389, respectively). CONCLUSIONS: In real-world clinical practice in Japan, UTUC patients who receive ACT after radical nephroureterectomy may be expected to have better cancer control than those who do not receive ACT.

Prognostic model using postoperative normalization of C-reactive protein levels in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy.

INTRODUCTION: To improve the prediction of outcomes in patients who will undergo radical nephroureterectomy (RN U) for upper tract urothelial carcinoma (UTUC), we investigated the preoperative prognostic factors and developed a risk classification model. METHODS: A total of 144 patients who underwent RNU with history of neither neoadjuvant nor adjuvant chemotherapy between 2008 and 2022 were retrospectively reviewed. Associations between perioperative/clinicopathologic factors and outcomes, including cancer-specific survival (CSS), were assessed. We specifically focused on preoperative serum C-reactive protein (CRP) and its postoperative normalization. RESULTS: Non-normalization of postoperative serum CRP level and pathologic T3 stage were identified as independent predictive factors of shorter CSS in univariate and multivariate analysis (p=0.0150 and 0.0037, hazard ratio: 3.628 and 4.470, respectively). We classified the patients into three groups using these factors and found that five-year CSS was 88%, 42.5%, and 0% in the low-risk group (zero factors), intermediate-risk group (one factor), and high-risk group (two factors), respectively (p<0.0001). CONCLUSIONS: Non-normalization of postoperative serum CRP level and pathologic T stage were identified as independent postoperative prognostic factors in patients with UTUC who underwent RNU. These factors can stratify three prognostic groups and may help urologists in clinical decision-making for adjuvant therapy.

Therapeutic outcome of combination therapy using immune-checkpoint inhibitors and tyrosine kinase inhibitors for metastatic non-clear-cell renal cell carcinoma.

INTRODUCTION: We aimed to clarify the therapeutic outcome of combination therapy using immune-checkpoint inhibitors (ICIs) and/or tyrosine kinase inhibitors (TKIs) for meta-static non-clear-cell renal cell carcinoma (nccRCC). METHODS: We have been retrospectively investigating the therapeutic efficacy and prognosis in 36 patients with metastatic nccRCC undergoing combination therapy using two ICIs, ipilimumab plus nivolumab (ICI-ICI), and ICI plus TKI (ICI-TKI), at Kobe University and affiliated institutions since 2018. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and adverse event (AE) were compared. RESULTS: The first-line regimen was ICI-ICI in 26 cases and ICI-TKI in 10 cases. The ORRs in the ICI-ICI and ICI-TKI groups were 34.6 and 30.0%, respectively (p=0.9433). The 50% PFS for the ICI-TKI group was 9.7 months, significantly longer than that for the ICI-ICI group (4.6 months, p=0.0499), and there was no significant difference in OS between groups (p=0.3984). There was no significant difference in the occurrence rate of AE for below grade 2 (p=0.8535), nor above grade 3 (p=0.3786) between the ICI-ICI and ICI-TKI groups. CONCLUSIONS: From our analysis of real-world data, a better outcome of PFS was expected in the ICI-TKI group compared with that in the ICI-ICI group, while there was no significant difference in OS or ORR.

The impact of primary region resection on the therapeutic outcome of combination regimens for metastatic renal cell carcinoma.

The present study aimed to clarify the relationship between the therapeutic outcome of combination regimens, including immune checkpoint inhibitors (ICIs) and/or tyrosine kinase inhibitors (TKIs), and cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC). The present study retrospectively assessed the association between treatment efficacy and prognosis with or without CN, and the timing of CN in 151 patients treated with combination regimens for mRCC who were categorized as intermediate/poor risk. The first-line regimens included the ICI-ICI and ICI-TKI regimens in 98 and 53 cases, respectively. In patients with recurrence after radical surgery (n=66), the 50% PFS times of the ICI-ICI and the ICI-TKI groups were 33.6 months and not reached (NR) (P=0.4032), respectively, and the 50% OS times were 53.7 months and NR (P=0.6886), respectively. Among the 38 patients with metastasis from the initial diagnosis who underwent upfront CN, the 50% PFS times of the ICI-ICI and the ICI-TKI groups were 10.5 and 8.2 months (P=0.5806), respectively, and the 50% OS times were NR and 15.8 months (P=0.0587), respectively. Among the 51 patients who did not receive upfront CN, the 50% PFS time of the ICI-TKI group was significantly higher than that in the ICI-ICI group (4.1 months and NR, respectively; P=0.0210), and the 50% OS times were 29.8 months and NR (P=0.7343), respectively. In conclusion, according to the analysis of real-world data, good therapeutic efficacy can be achieved with any regimen in patients with recurrence after radical surgery. In addition, improved results could be achieved through treatment with ICI-TKI in patients without upfront CN.