Metastatic renal cell carcinoma: Synchronous vs. metachronous metastatic disease and its impact on cancer control in the IO-combination era-Real world experiences from a multi-institutional cohort.

Purpose: The association of metastatic timing (synchronous vs. metachronous) in metastatic renal cell carcinoma (mRCC) with survival outcomes in the immunooncology (IO) combination therapy era is not well understood to date. To assess progression-free survival (PFS) and overall survival (OS) based on the time to metastasis in mRCC patients treated with IO therapy combination therapies.

Material and methods: Data from a multi-center retrospective German patient cohort was used to compare synchronous metastasis (occurring within 3 months of the initial cancer diagnosis) with metachronous metastasis (4-24 months vs. ≥25 months). PFS and OS were analyzed using Kaplan-Meier curves. Cox multivariable regression analyses were adjusted for baseline characteristics.

Results: The cohort comprised 381 mRCC patients treated with 1st-line IO-combination therapies, categorized by time of metastatic onset: 167 (44%) in 0-3 months, 94 (25%) in 4 to 24 months, and 120 (31%) in ≥25 months. Differences in initial diagnosis age, ECOG performance status, local kidney treatment, and systemic treatment type were noted (all P < 0.05). Median PFS was 10.6 months for 0 to 3 months, 13.8 months for 4 to 24 months, and 16.8 months for ≥25 months (log-rank test: P = 0.028). Here, ≥25 months group showed significantly prolonged PFS in univariable (HR: 0.63; 95% CI:0.45-0.83) and multivariable Cox regression (HR: 0.64; 95% CI:0.41-0.99). Median OS was 28.0 months for 0 to 3 months, 39.7 months for 4 to 24 months, and 49.3 months for ≥25 months (P < 0.001). Multivariable Cox regression showed prolonged OS for both 4 to 24 months (HR: 0.45; 95% CI:0.26-0.76) and ≥25 months (HR: 0.56; 95% CI:0.33-0.95).

Conclusions: Within this contemporary cohort of mRCC patients treated with IO-combination therapy, timing of metastatic disease and initiation of systemic treatment was associated with OS.

Patient summary: This study examined the impact of when metastases occur on survival outcomes in kidney cancer patients treated with first-line immune-combination therapies. The findings show that a longer interval before the development of metastases is associated with better outcomes.