髙原 健

PURPOSE: The purpose of this study is to determine the utility of the CANLPH score as a predictive biomarker for patients with advanced and metastatic renal cell carcinoma (a/mRCC). By validating its prognostic value, this study aims to contribute to more personalized treatment strategies for a/mRCC. METHODS: In a multicenter retrospective study by the JK-FOOT consortium, we analyzed data from 309 a/mRCC patients undergoing ICI-based therapy. The CANLPH score-a composite marker of C-reactive protein to albumin ratio (CAR), neutrophil to lymphocyte ratio (NLR), and platelet to hemoglobin ratio (PHR)-for its prognostic accuracy in predicting cancer-specific survival (CSS). Advanced statistical methods, including receiver operating characteristic (ROC) curve analysis, Cox proportional-hazard regression, and Harrell's concordance index (C-index), were employed to assess its predictive capacity against established factors. RESULTS: The median follow-up period was 17 months, revealing two-year and five-year overall survival rates of 76.8% and 62.4%, respectively, with CSS rates at 78.3% and 66.2%. The CANLPH score well stratified survival outcomes of ICI-based treatment for RCC patients (HR 5.71; P < 0.0001). C-index analysis demonstrated that the CANLPH score had the highest predictive potency for CSS among models, including IMDC score. Multivariate analysis confirmed the CANLPH score (HR, 5.59; P = 0.0007) and Karnofsky performance status (HR, 2.59; P = 0.0032) as independent prognostic factors for CSS. CONCLUSIONS: The CANLPH score emerges as a critical tool in the a/mRCC therapeutic landscape, enabling precise prediction of patient outcomes with ICI-based therapies. Limitations include the retrospective design and the single national cohort. Prospective validation studies are warranted.

BACKGROUND: Metastatic nonclear cell renal cell carcinoma (nccRCC) is a heterogeneous disease with poor prognosis. The clinical characteristics and prognostic factors of immuno-oncology (IO) combination therapy for nccRCC are not well known. This study analyzed patients with metastatic nccRCC treated with IO combination therapy. METHODS: We retrospectively collected data from 447 patients with metastatic RCC treated with IO-based combination therapy as first-line treatment between September 2018 and July 2023 in a Japanese multicenter study. The primary endpoints were objective response rate, progression-free survival (PFS), and overall survival (OS), comparing groups treated with IO-IO and IO-tyrosine kinase inhibitor (TKI) therapies. RESULTS: Seventy-five patients with metastatic nccRCC were eligible for analysis: 39 were classified into the IO-IO group and 36 into the IO-TKI group. Median PFS was 5.4 months (95% CI: 1.6-9.1) for the IO-IO group and 5.6 (95% CI: 3.4-12.0) for the IO + TKI group. Median OS was 24.2 months (95% CI: 7.5-NA) for the IO-IO group and 23.4 (95% CI: 18.8-NA) for the IO + TKI group, with no significant difference. In univariate analysis, International Metastatic Renal Cell Carcinoma Database Consortium scores, Karnofsky performance status, neutrophil-to-lymphocyte ratio, and the presence of liver metastases were significantly associated with OS, whereas in multivariate analysis, only the presence of liver metastases was significantly associated with OS (P = .035). CONCLUSIONS: There was no significant difference in OS or PFS between IO-IO and IO-TKI combination therapy as first-line treatment for patients with nccRCC. Liver metastasis is a poor prognostic factor for such patients.

PURPOSE: Immune checkpoint inhibitor (ICI)-based combination therapy is a standard systemic treatment for metastatic renal cell carcinoma (mRCC). Although differential pharmacologic action between ICI+ICI and ICI+tyrosine kinase inhibitor (TKI) combinations may affect outcomes, comparative studies using real-world data are few. METHODS: We retrospectively analyzed the records of 447 mRCC patients treated with 1st-line ICI-based combinations at multiple institutions between January 2018 and August 2023, and selected 320 patients diagnosed with clear cell RCC (ccRCC) for further study. Cohorts were matched using one-to-one propensity scores based on IMDC risk classification. Overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), and treatment-related adverse events (TrAE) were compared. RESULTS: The matching process yielded 228 metastatic ccRCC patients treated with ICI+ICI (n = 114) or ICI+TKI (n = 114). Median OS was 53 months (95%CI: 33-NA) in patients treated with ICI+ICI and was not reached (95%CI: 43-NA) with ICI+TKI (P = 0.24). Median PFS was significantly shorter for ICI+ICI (13 months, 95%CI: 7-25) than for ICI+TKI (25 months, 95%CI: 13-NA) (P = 0.047). There were no differences in second-line PFS for sequential therapy after 1st-line combinations of ICI+ICI or ICI+TKI (6 vs. 8 months, P = 0.6). There were no differences in ORR between the 2 groups (ICI+ICI: 51% vs. ICI+TKI: 55%, P = 0.8); the progressive disease (PD) rate was significantly higher in patients treated with the ICI+ICI combination (24% vs. 11%, P = 0.029). The rate of any grade TrAE was significantly higher in patients treated with ICI+TKI (71% vs. 85%, P = 0.016), but we found no differences in severe TrAE between the 2 groups (39% vs. 36%, P = 0.8). CONCLUSIONS: In a matched cohort of real-world data, we confirmed comparable OS benefits between ICI+ICI and ICI+TKI combinations. However, differential clinical behaviors in terms of PFS, PD rates, and TrAE between ICI-based combinations may enrich clinical decision-making.

OBJECTIVE: The aim of this study was to compare prognostic outcomes of administering first- or second-generation androgen receptor signaling inhibitors in non-metastatic castration-resistant prostate cancer and to find prognostic indicators. METHODS: This retrospective study included 198 patients with non-metastatic castration-resistant prostate cancer from 14 institutions associated with Tokai Urologic Oncology Research Seminar. Forty-two patients were treated with combined androgen blockade using first-generation inhibitors (bicalutamide or flutamide), and 156 were treated with second-generation inhibitors (abiraterone/enzalutamide or apalutamide/darolutamide) after primary androgen deprivation therapy failure. We compared survival outcomes of combined androgen blockade using first-generation inhibitors and second-generation inhibitor treatments, and analyzed clinicopathological or serum parameters and survival outcome. RESULTS: Combined androgen blockade and second-generation androgen receptor signaling inhibitor groups demonstrated median progression-free survival of 10.2 (95% confidence interval: 5.5-12.3) and 26.0 (95% confidence interval: 21.9-38.4; P < 0.001) months, respectively. Cut-off levels for clinical biomarkers were targeted to <0.2 ng/ml prostate-specific antigen levels 3 months after treatment initiation for non-metastatic castration-resistant prostate cancer; the patient group that achieved this showed better progression-free survival (median 14.7 months, 95% confidence interval: 10.3-23.9 not achieved, median not applicable, 95% confidence interval: 24.6-not applicable achieved; P < 0.00001). Multivariate analysis revealed significant prognostic factors: second-generation androgen receptor signaling inhibitor as first-line treatment (odds ratio: 5.05, 95% confidence interval: 1.54-16.6) and a high hemoglobin level (odds ratio: 2.92, 95% confidence interval: 1.26-6.76). CONCLUSIONS: Our findings suggested prostate-specific antigen < 0.2 ng/ml after 3 months may be a practical prognostic indicator of survival outcomes in non-metastatic castration-resistant prostate cancer. Patients showing a high hemoglobin level should be intensively treated with second-generation androgen receptor signaling inhibitors rather than combined androgen blockade using first-generation inhibitors.