Molecular risk adapted treatment modification in patients with metastatic hormone sensitive prostate cancer. (MAP-PROSTATE).

Prostate cancer is the second most common malignancy worldwide. In India, it accounts for 6.1% of all cancers diagnosed in men. The estimated incidence in 2020 was 41,532 new cases (per year), however, it is estimated to reach close to fifty-thousand new cases by 2025. At our institute we see approximately 300 to 400 new cases of metastatic hormone sensitive prostate cancer (mHSPC) per year, therefore, the burden of prostate cancer cases in India is high. Since the initial observation by Huggins and Hodges in 1941 that prostate cancer is androgen dependent and can be successfully treated with either surgical or medical castration, hormonal therapy has been the mainstay of treatment for men with newly diagnosed metastatic prostate cancer. Castration-resistant prostate cancer develops in the majority of men within 1–3 years, with the result that median survival among patients with metastatic prostate cancer is ~ 3–4 years. Efforts at improving overall survival in the metastatic setting have, until recently, been directed towards patients with metastatic castrate-resistant prostate cancer (mCRPC) with significant improvements seen during the past decade. This is evidenced by the ability of six agents to increase overall survival in mCRPC. This includes the androgen biosynthesis inhibitor abiraterone acetate, the androgen receptor inhibitor, enzalutamide, immunotherapy with sipulecel-T, cabazitaxel and docetaxel chemotherapy and the radioisotope radium-223. However, each agent increases overall survival by a few months at best and despite these advances, metastatic prostate cancer remains a lethal disease. 

In this study, we propose the utilization of baseline tumour NGS testing to identify patients with chemotherapy-sensitive, hormone-sensitive, or PARPi-sensitive disease, to enable effective modification/de-escalation of standard first-line triplet therapy without compromising survival outcomes. Treatment modification or de-escalation will safeguard potent second-line drugs for treatment of progressive disease.