Influence of metastatic sites and burden on oncological outcomes in patients progressing to metastatic castration resistant prostate cancer.

Purpose: Metastatic castration-resistant prostate cancer (mCRPC) patients harbor reduced life expectancy after first-line treatment progression. Currently, no information is available regarding the influence of metastatic sites and osseous burden on progression-free (PFS) and overall survival (OS) of mCRPC patients.

Methods: We relied on the Frankfurt Metastatic Cancer Database of the Prostate (FRAMCAP) database to select patients progressing to mCRPC and stratified them according to lymph node vs. osseous vs. visceral metastatic sites. Moreover, we stratified osseous mCRPC patients regarding the number of metastatic lesions. Endpoints were PFS and OS in uni- and multivariable Cox regression models.

Results: Of 363 patients, 9.4% harbored M1a vs. 78% M1b vs. 12% M1c mCRPC with significantly higher PSA in M1b (9 vs. 22 vs. 8ng/ml). Rates of DeNovo (15% vs. 60% vs. 56%) were significantly lower in the M1a mCRPC group, compared to M1b and M1c (p < 0.001). In PFS analyses, a median of 12.7 vs. 10.1 vs. 15.9 months for M1a vs. M1b vs. M1c mCRPC was observed (p > 0.05). In multivariable Cox regression models, M1c mCRPC was independently at higher risk for progression (hazard ratio [HR]: 5.93, p = 0.048), relative to M1a. Regarding OS, significant differences were observed (p = 0.002), with median OS of 58 vs. 42 vs. 25 months for M1a vs. M1b vs. M1c mCRPC and corresponding HRs of 1.54 (p = 0.11) and 2.76 (p < 0.01). In multivariable models M1c mCRPC was associated with higher risk of death (HR: 3.56, p = 0.049), relative to M1a. No differences were observed after stratification according to number of bone lesions (all p ≥ 0.05).

Conclusion: M1c mCRPC patients are independently at higher risk for progression and death, while M1a patients harbor best cancer-control outcomes.