Personalizing approaches to the management of metastatic hormone sensitive prostate cancer: role of advanced imaging, genetics and therapeutics

by Selleckchem | Jun 15 2023

Purpose: To summarize contemporary and emerging strategies for the diagnosis and management of metastatic hormone sensitive prostate cancer (mHSPC), focusing on diagnostic testing and therapeutics.

Methods: Literature review using PUBMED-Medline databases as well as clinicaltrials.gov to include reported or ongoing clinical trials on treatment for mHSPC. We prioritized the findings from phase III randomized clinical trials, systematic reviews, meta-analyses and clinical practice guidelines.

Results: There have been significant changes to the diagnosis and staging evaluation of mHSPC with the integration of increasingly accurate positron emission tomography (PET) imaging tracers that exceed the performance of conventional computerized tomography (CT) and bone scan. Germline multigene testing is recommended for the evaluation of patients newly diagnosed with mHSPC given the prevalence of actionable alterations that may create candidacy for specific therapies. Although androgen deprivation therapy (ADT) remains the backbone of treatment for mHSPC, approaches to first-line treatment include the integration of multiple agents including androgen receptor synthesis inhibitors (ARSI; abiraterone) Androgen Receptor antagonists (enzalutamide, darolutamide, apalautamide), and docetaxel chemotherapy. The combination of ADT, ARSI, and docetaxel chemotherapy has recently been evaluated in a randomized trial and was associated with significantly improved overall survival including in patients with a high burden of disease. The role of local treatment to the prostate with radiation has been evaluated in randomized trials with additional studies underway evaluating the role of cytoreductive radical prostatectomy.

Conclusion: The staging and initial management of patients with mHSPC has undergone significant advances in the last decade with advancements in the diagnosis, treatment and sequencing of therapies.

Comments:

Recent advancements in the diagnosis and management of metastatic hormone-sensitive prostate cancer (mHSPC) have led to significant improvements in patient care. The integration of more accurate positron emission tomography (PET) imaging tracers has enhanced the diagnosis and staging evaluation of mHSPC, surpassing the performance of conventional computerized tomography (CT) and bone scans.

Germline multigene testing is now recommended for newly diagnosed mHSPC patients due to the high prevalence of actionable alterations, which can guide specific therapeutic options. While androgen deprivation therapy (ADT) remains the standard treatment for mHSPC, first-line approaches now involve the integration of multiple agents.

These agents include androgen receptor synthesis inhibitors (ARSI) such as abiraterone, androgen receptor antagonists like enzalutamide, darolutamide, and apalutamide, as well as docetaxel chemotherapy. A recent randomized trial demonstrated that combining ADT, ARSI, and docetaxel chemotherapy significantly improved overall survival, even in patients with a high burden of disease.

The role of local treatment to the prostate with radiation has also been evaluated in randomized trials, and ongoing studies are assessing the potential benefits of cytoreductive radical prostatectomy in mHSPC.

In conclusion, significant advances have been made in the staging and initial management of patients with mHSPC in the last decade. These advancements have improved the diagnosis, treatment, and sequencing of therapies, leading to better outcomes for patients with mHSPC.