Metastasis-free survival as a predictor of overall survival in non-metastatic castration-resistant prostate cancer.

Abstract

201 Background: Recent trials have shown that apalutamide and enzalutamide can improve metastasis free survival (MFS) in advanced non-metastatic (M0) castrate-resistant prostate cancer (CRPC). MFS is a novel clinical endpoint, demonstrated to be a strong predictor of overall survival (OS) for localized prostate cancer, yet it is unknown if this is also true for M0 CRPC. Our aim was to determine how strongly MFS in M0 CRPC correlates with OS in a real world population. Secondary analyses evaluated whether a rapid PSA-doubling time (PSADT), of ≤10 months, impacts outcomes. Methods: We performed an analysis of patients diagnosed with advanced prostate cancer, followed at the Tom Baker Cancer Centre, in Calgary, Alberta from 2001-2017. Patients were excluded if they did not develop M0 CRPC. MFS and OS were measured using the Kaplan-Meier method and the log-rank test was used to compare outcomes based on PSADT. Correlation between OS and MFS was determined using Pearson Correlation and Kendall’s Tau-B. Results: A total of 1310 patients were identified with advanced prostate cancer, of which 87 developed M0 CRPC. The median age of diagnosis of M0 CRPC was 72 years, with a median Gleason score of 7.0, initial PSA of 10.4, and PSADT of 5.1 months. Only 6 patients were treated with second-generation anti-androgens or chemotherapy. Median MFS and OS after M0 CRPC diagnosis were 44.1 and 83.7 months, respectively. Pearson Correlation between MFS and OS was strong with a coefficient of 0.850 (p < 0.001); with non-parametric Kendall’s Tau, correlation was also strong with a coefficient of 0.632 (p < 0.001). PSADT ≤10 months was identified in 70 patients, and associated with a significantly shorter MFS, compared to a PSADT > 10 months (40.2 vs. 90.4 months; p = 0.001), as well as shorter OS (76.2 vs. 104.3 months; p = 0.008). Conclusions: MFS for M0 CRPC is strongly correlated with OS in a real world population. PSADT of ≤10 months seems to be a useful prognostic tool in estimating MFS and OS in patients with M0 CRPC. MFS was better than expected even in patients with a PSADT of ≤10 months, which may due to our adherence to the biochemical definition of castration-resistant disease, as well as lack of standard imaging intervals in the real world.

Patient and caregiver benefit‐risk preferences for nonmetastatic castration‐resistant prostate cancer treatment

“…33 OS was ultimately selected because it was more clinically meaningful for patients who had difficulties drawing inference that MFS was a strong surrogate or predictor of OS as demonstrated in several analyses. 34,35 Furthermore, although MFS was used as an endpoint in trials, the definition varied. We also observed in our qualitative interviews that patients, caregivers, and physicians, all viewed OS as the most important efficacy attribute.…”

The correlation between metastasis-free survival and overall survival in non-metastatic castration resistant prostate cancer patients from the Medical Data Vision claims database in Japan

“…Although the results of this analysis demonstrate a correlation between MFS and OS that is moderate to strong, accumulation of additional data can further strengthen these findings. This is demonstrated in the research conducted in Canada that reports strong correlation between MFS and OS with longer follow-up of the patients 24 . When MFS and OS events have further accumulated, the results from subgroup analysis as by PSADT at the index date may provide stronger insights.…”

Are We Ready for Migrastatics?

“…Recent publications further support the redirection of the research and development focus on MFS as an accurate evaluative measure for cancer therapies. Of significance is the correlation of MFS with the overall survival (OS) of patients with nmCRPC [7]. It has recently been shown that metastasis development is associated with a significantly greater risk of death in men with high-risk nmCRPC; hence, MFS is predictive of OS [7].…”

“…Of significance is the correlation of MFS with the overall survival (OS) of patients with nmCRPC [7]. It has recently been shown that metastasis development is associated with a significantly greater risk of death in men with high-risk nmCRPC; hence, MFS is predictive of OS [7]. When using MFS instead of OS as a clinical trial endpoint, investigators and clinicians will be able to observe the prognostic criteria earlier, allowing a more rapid evaluation of new anti-metastasis therapies.…”