Risk stratification criteria show good prognostic value in CRPC, but not enough to guide treatment

The risk stratification criteria used in the CHAARTED and LATITUDE trials can accurately assess prognosis in patients with castration-resistant prostate cancer (CRPC), but are insufficient to differentiate between the therapeutic outcomes of androgen receptor pathway inhibitors (ARPI) and docetaxel, a new study has found.

In CHAARTED, patients were classified as high-risk if they had visceral metastasis or four or more bone metastases beyond the spine and pelvis. Meanwhile, LATITUDE defined high-risk as having at least two of the following: Gleason score ≥8, bone metastases of three or more, or visceral metastasis.

The present study enrolled 215 CRPC patients, of whom 110 (51.2 percent) and 93 (43.3 percent) were deemed to be high-risk according to the CHAARTED and LATITUDE criteria, respectively. Treatment was conducted with either ARPIs (abiraterone plus prednisolone, or enzalutamide) or docetaxel.

Grouping patients according to the CHAARTED risk criteria found a substantial difference in progression-free survival (PFS) in favour of those deemed low-risk (10.3 vs 4.5 months). A similar pattern was reported for overall survival (OS; 44.8 vs 17.4 months). Stratifying according to LATITUDE definitions had the same effect for PFS (9.9 vs 4.8 months) and OS (37.4 vs 17.4 months).

Multivariate analysis confirmed that both the CHAARTED and LATITUDE risk definitions were significant prognostic predictors of PFS, while only the CHAARTED criteria predicted OS.

However, when evaluating the utility of the CHAARTED and LATITUDE definitions to differentiate clinical outcomes between ARPI and docetaxel, the researchers detected no significant effect, suggesting that both risk-stratification criteria were underpowered to assess the therapeutic effects of either agent.

“For the first time, this study indicated that risk stratification by the LATITUDE as well as CHAARTED criteria in CRPC is prognostic of disease progression and OS. However, those criteria were not useful in choosing treatment using ARPI or docetaxel,” the researchers said.