In this multicenter study, 716 mCSPC patients were included, receiving either ADT alone, combined androgen blockade (CAB), or ARSI doublet therapy. The study categorized patients based on their metastatic sites, evaluating outcomes such as time to castration-resistant prostate cancer (CRPC) development, progression-free survival 2 (PFS2), cancer-specific survival (CSS), and overall survival (OS). Importantly, the analysis highlighted the unique behavior of lung metastasis in mCSPC.
Key findings revealed that patients with lung-only metastases had significantly better outcomes compared to those with other visceral metastases. Multivariate analysis demonstrated that while bone metastasis volume was a critical factor influencing CRPC-free survival, lung metastasis status had a lesser impact on survival outcomes, particularly in patients with bone metastases. These findings challenge traditional views, where any visceral metastasis typically denotes high-volume disease,4,5 suggesting that lung metastases might not always represent a high-volume risk factor. Moreover, patients with bone metastases, regardless of lung metastasis presence, exhibited similar prognoses, suggesting that treatments targeting low-volume bone disease may suffice, even with the presence of lung metastases. This nuanced understanding allows for more tailored treatment strategies in clinical practice, particularly in the context of ARSI doublet therapy.
While the study provides valuable insights, it also highlights several limitations, including the relatively short follow-up period and the lack of data on triplet therapy, which was recently approved.6,7 Further studies with longer follow-ups and more extensive cohorts are necessary to fully assess the long-term benefits of various treatments and refine risk stratification in mCSPC.
In conclusion, this study emphasizes the importance of considering metastatic site distribution when assessing prognosis and selecting treatment strategies for mCSPC. The findings suggest that lung metastases, especially when isolated, may not carry the same poor prognosis as other visceral metastases, offering hope for more personalized and effective management of mCSPC in the era of ARSI therapies.
Written by: Fumihiko Urabe, MD, PhD, Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
References:
- Westaby D, Fenor de La Maza MLD, Paschalis A, Jimenez-Vacas JM, Welti J, de Bono J, et al. A New Old Target: Androgen Receptor Signaling and Advanced Prostate Cancer. Annu Rev Pharmacol Toxicol. 2022;62:131-53.
- Obinata D, Yamada Y, Sumiyoshi T, Tanegashima T, Watanabe R, Kobayashi H, et al. Recent advances in basic research on prostate cancer: Where we are heading? Int J Urol. 2024.
- Urabe F, Tashiro K, Muramoto K, Yanagisawa T, Katsumi K, Takahashi H, et al. Locations of metastases in and oncological outcomes of patients with metastatic castration-sensitive prostate cancer: Real-world data from a multicenter study. Urol Oncol. 2025.
- Kyriakopoulos CE, Chen YH, Carducci MA, Liu G, Jarrard DF, Hahn NM, et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis of the Randomized Phase III E3805 CHAARTED Trial. J Clin Oncol. 2018;36(11):1080-7.
- Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. 2015;373(8):737-46.
- Smith MR, Hussain M, Saad F, Fizazi K, Sternberg CN, Crawford ED, et al. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N Engl J Med. 2022;386(12):1132-42.
- Urabe F, Imai Y, Goto Y, Tashiro K, Hashimoto M, Yoshihara K, et al. Real-world evidence of triplet therapy efficacy in patients with metastatic castration-sensitive prostate cancer: a Japanese multicenter study. Jpn J Clin Oncol. 2024;54(11):1208-13.