Management of Advanced Prostate Cancer in the Precision Oncology Era

Abstract

Prostate cancer (PC) is the second leading cause of cancer death in men in the United States. While diversified and improved treatment options for aggressive PC have improved patient outcomes, metastatic castration-resistant prostate cancer (mCRPC) remains incurable and an area of investigative therapeutic interest. This review will cover the seminal clinical data supporting the indication of new precision oncology-based therapeutics and explore their limitations, present utility, and potential in the treatment of PC. Systemic therapies for high-risk and advanced PC have experienced significant development over the past ten years. Biomarker-driven therapies have brought the field closer to the goal of being able to implement precision oncology therapy for every patient. The tumor agnostic approval of pembrolizumab (a PD-1 inhibitor) marked an important advancement in this direction. There are also several PARP inhibitors indicated for patients with DNA damage repair deficiencies. Additionally, theranostic agents for both imaging and treatment have further revolutionized the treatment landscape for PC and represent another advancement in precision medicine. Radiolabeled prostate-specific membrane antigen (PSMA) PET/CT is rapidly becoming a standard of care for diagnosis, and PSMA-targeted radioligand therapies have gained recent FDA approval for metastatic prostate cancer. These advances in precision-based oncology are detailed in this review.

Keywords: PARP inhibitors; PSMA; advanced prostate cancer; biomarkers; chemotherapy; genomic selection; immunotherapy; metastatic prostate cancer; radioligand therapy; theranostics.

Figure 1

Treatment sequencing in recurrent/advanced prostate cancer. A core standard of care for metastatic disease is androgen deprivation therapy (ADT) in combination with at least one additional therapy. This review focuses on the therapeutic options upon disease progression following treatment. Abbreviations: biochemical recurrence, BCR; androgen deprivation therapy, ADT; androgen receptor-signaling inhibitor, ARSI; prostate-specific membrane antigen, PSMA; positron emission tomography/computational tomography, PET/CT; homologous recombination repair deficiency, HRRd; mismatch repair deficiency, MMRd; tumor mutational burden-high, TMB-H; microsatellite instability-high, MSI-H.