Real-World Outcomes and Molecular Profiling for Patients with Metastatic Castration-resistant Prostate Cancer with Lung Metastases: A Long-term Multicenter Experience.

Background and objective: The prognostic impact of lung metastases (LuMs) in metastatic castration-resistant prostate cancer (mCRPC) remains poorly defined. Our aim was to evaluate the clinical and molecular characteristics of patients with mCRPC with LuMs and their outcomes.

Methods: This retrospective multicenter study included 930 patients with mCRPC across 13 centers in Italy. The primary endpoint was the impact of LuMs on overall survival (OS), progression-free survival (PFS), and prostate-specific antigen (PSA) response. As a secondary endpoint, next-generation sequencing for a subgroup with LuMs was used to identify molecular characteristics that might be useful in guiding personalized therapy.

Key findings and limitations: Among mCRPC patients treated with an androgen receptor signaling inhibitor, we observed no significant differences in median OS or PFS and PSA response between the LuMs group and the group with bone ± lymph node metastases. Multivariable analyses revealed that only Eastern Cooperative Oncology Group performance status, PSA level, prior docetaxel treatment, and number of metastatic lesions were significant independent factors for both OS and PFS. Comparison of the groups with LuMs only versus liver metastases revealed a significant association between LuMs and a longer OS (15 vs 10 mo; p = 0.002) and PFS (9 vs 5 mo; p = 0.002). The proportion of patients with a ≥50% PSA decline was higher in the LuMs group (odds ratio 3.57, 95% confidence interval 1.37-9.45; p = 0.004). Molecular profile results showed that TP53 mutations accounted for a lower proportion of the pathogenic variants in LuMs than in liver metastases (15% vs 89%). Limitations include the retrospective design and clinical heterogeneity of the population, in addition to unavailability of metastatic biopsies for more in-depth analyses.

Conclusions and clinical implications: Our findings suggest that patients with LuMs in mCRPC exhibit clinical and molecular features more similar to those with bone ± lymph nodal metastases than to patients with liver metastases. Further prospective studies are warranted.