Efficacy of Combination Therapy With Radium-223 and Enzalutamide in Castration-resistant Prostate Cancer With Bone Metastases.

BACKGROUND/AIM: Radium-223 therapy has been reported to improve prognosis in patients with castration-resistant prostate cancer (CRPC) and bone metastases. Occasionally, radium-223 and androgen receptor signaling inhibitors (ARSIs) are used in combination for disease control, but the efficacy of this combination is unclear. This study assessed the efficacy of the addition of enzalutamide in patients treated with radium-223. PATIENTS AND METHODS: We included patients with CRPC and bone metastases who were treated with radium-223 at our institution. Patients were assigned to the enzalutamide combination group or non-combination group. We compared progression-free survival (PFS), overall survival (OS), and the completion rate of radium-223 between the two groups. RESULTS: In total, 39 patients with CRPC were included in this retrospective study. The median follow-up duration was 8.8 months. The enzalutamide combination and non-combination groups included 22 (56.4%) and 17 patients (43.6%), respectively. Median PFS was 11.3 months [95% confidence interval (CI)=3.9-19.9] in the combination group, versus 3.0 months (95%CI=1.9-5.5) in the non-combination group (p=0.004). Median OS did not significantly differ between the groups. The radium-223 completion rate was higher in the combination group than in the non-combination group (72.7% vs. 35.3%, p=0.026). CONCLUSION: The combined use of enzalutamide with radium-223 therapy improved PFS and treatment completion rates in patients with CRPC and bone metastases. This combination may be associated with a more favorable prognosis.

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.

Prognostic Value of Serum Soluble PD-L1 in Metastatic Renal Cell Carcinoma Patients Treated With Nivolumab.

BACKGROUND/AIM: Increasing availability of effective treatment options for metastatic renal cell carcinoma (mRCC) has highlighted the importance of identifying predictors of treatment response. Although PD-L1 expression in renal cancer has been reported as a predictor of treatment response and prognosis, its assessment by immunohistochemistry is invasive and difficult to perform repeatedly. Soluble PD-L1 (sPD-L1) has recently been proposed as a predictive biomarker for several tumour types. Therefore, we evaluated sPD-L1 levels in patients with mRCC treated with nivolumab and investigated its association with treatment response. PATIENTS AND METHODS: We performed a prospective single-arm study in patients with mRCC treated with nivolumab as second line or later therapy. We measured serum sPD-L1 before and during treatment, classified patients based on baseline values (sPDL1 ≥0.23 ng/ml vs. <0.23 ng/ml) and compared outcomes between the two groups. RESULTS: A total of 43 patients with mRCC were included in this study, with 17 (39.5%) classified as low sPD-L1 and 26 (60.5%) as high sPD-L1. The International Metastatic RCC Database Consortium risk score was significantly poorer in the high sPD-L1 group. The objective response rate was significantly higher (41.2% vs. 7.7%) and overall survival significantly longer (p=0.0323) in the low group compared to the high group. There were no significant differences in progression-free survival between the two groups. CONCLUSION: Our study findings indicate that sPD-L1 might be a predictor of treatment response to nivolumab in patients with mRCC.

Comparison of robot-assisted partial nephrectomy for complex (RENAL scores ≥10) and non-complex renal tumors: A single-center experience.

OBJECTIVES: To compare functional and surgical outcomes of robot-assisted partial nephrectomy for complex tumors with RENAL scores ≥10 and non-complex tumors at a single academic institution. METHODS: We retrospectively analyzed the data of all patients who underwent robot-assisted partial nephrectomy at Kobe University Hospital (Kobe, Hyogo, Japan) from 2011 to 2020. Functional and surgical outcomes for complex tumors (RENAL score ≥10) were compared with those of patients with non-complex tumors (RENAL <10). Outcomes analyzed included blood loss, warm ischemia time, console time, perioperative complications, and preoperative and postoperative renal function. RESULTS: A total of 348 patients were included in our present study, with a median follow-up time of 35.1 months. Of these, 299 patients (85.9%) had non-complex tumors and 49 patients (14.1%) had complex tumors. Warm ischemia time and console time were significantly longer in the complex tumors group. Major perioperative complications (Clavien-Dindo classification system ≥3) were significantly more frequent in the complex tumors group than the non-complex tumor group (16.3% vs 5.7%, P = 0.018). Postoperative preservation of estimated glomerular filtration rate and percentage of chronic kidney disease upstage by 1 year were significantly inferior in the complex tumors group. The positive surgical margin rate was 0% and 0.3% in the complex and non-complex tumor groups, respectively. There were no significant differences in recurrence-free survival between the two groups (P = 0.11). CONCLUSIONS: Robot-assisted partial nephrectomy for complex renal tumors is safe, with no difference in oncological outcomes, although more postoperative complications and decreased renal function can be observed than non-complex tumors.