PD-1/PD-L1 for prostate cancer: from clinical trials to practice

Area of Science:

• Oncology
• Immunotherapy
• Genitourinary Cancers

Background:

• Immune checkpoint inhibitors (ICIs), particularly anti-PD-(L)1 antibodies, have transformed cancer treatment.
• Prostate cancer (PC) has historically demonstrated limited efficacy with ICI therapy.
• Understanding predictive biomarkers is crucial for optimizing ICI treatment in PC.

Purpose of the Study:

• To review clinical trials of PD-(L)1 inhibitors in prostate cancer.
• To identify patient subsets who may benefit from ICI therapy.
• To discuss the role of molecular profiling in guiding treatment decisions.

Main Methods:

• Comprehensive literature review of clinical trials involving PD-(L)1 inhibitors in prostate cancer.
• Analysis of treatment outcomes based on patient selection and tumor characteristics.
• Evaluation of the impact of specific genetic mutations on ICI response.

Main Results:

• PD-(L)1 inhibitors, alone or in combination, show limited benefit in unselected prostate cancer patients.
• A subset of patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) tumors may respond to PD-(L)1 inhibitors.
• High tumor mutational burden (TMB-H) is also associated with potential benefit, albeit to a lesser extent.

Conclusions:

• Current PD-(L)1 inhibitor strategies offer minimal benefit for the general prostate cancer population.
• Genomic testing to identify MSI-H/dMMR or TMB-H mutations is essential for patient selection.
• Targeted application of PD-(L)1 inhibitors in molecularly selected PC patients may improve outcomes.