Abstract
Recently, checkpoint inhibitors have been investigated in metastatic prostate cancer, however their overall effect is unclear and needs to be further investigated. Objectives: The aim of this systematic review is to investigate the oncological response of metastatic castration-resistant prostate cancer patients to immune checkpoint inhibitors. Methods: Based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement, a systematic review of the literature was conducted through online electronic databases and the American Society of Clinical Oncology (ASCO) Meeting Library. Eligible publications were selected after a staged screening and selection process. RevMan 5.4 software was employed to run the quantitative analysis and forest plots. Risk of bias assessment was conducted using the Cochrane tool and Newcastle–Ottawa Scale for the randomized and non-randomized trials, respectively. Results: From the 831 results retrieved, 8 studies including 2768 patients were included. There was no significant effect on overall survival (OS) (overall response (OR) = 0.98; Z = 0.42; p = 0.67). Meanwhile, progression-free survival (PFS) was significantly better with immune checkpoint inhibitors administration (OR = 0.85; Z = 3.9; p < 0.0001). The subgroup analysis for oncological outcomes based on programmed death ligand 1 (PD-L1) positivity status displayed no significant effect, except on prostate-specific antigen response rate (PSA RR) (OR = 3.25; Z = 2.29; p = 0.02). Based on DNA damage repair (DDR), positive patients had a significantly better PFS and a trend towards better OS and overall response rate (ORR); the ORR was 40% in positive patients compared to 20% in the negative patients (OR = 2.46; Z = 1.3; p = 0.19), while PSA RR was 23.5% compared to 14.3% (OR = 1.88; Z = 0.88; p = 0.38). Better PFS was clearly associated with DDR positivity (OR = 0.70; Z = 2.48; p = 0.01) with a trend towards better OS in DDR positive patients (OR = 0.71; Z = 1.38; p = 0.17). Based on tumor mutation burden (TMB), ORR was 46.7% with high TMB versus 8.8% in patients with low TMB (OR = 11.88; Z = 3.0; p = 0.003). Conclusions: Checkpoint inhibitors provide modest oncological advantages in metastatic castration-resistant prostate cancer. There are currently no good predictive indicators that indicate a greater response in some patients.
Highlights
Prostate cancer was the second most frequent cancer and the fifth largest cause of cancer-related deaths among males globally in 2020 [1]
Aside from androgen deprivation therapy (ADT), which is the cornerstone of metastatic prostate cancer care, therapeutic options mostly consist of either innovative hormonal therapies or taxane-based chemotherapy [5,6]
Castrate-resistant prostate cancer (CRPC) develops when tumors cease responding to androgen deprivation
Summary
Prostate cancer was the second most frequent cancer and the fifth largest cause of cancer-related deaths among males globally in 2020 [1]. Therapeutic options for advanced prostate cancer have expanded in the last few years as a result of a better knowledge of the molecular processes that underpin metastatic spread, the crucial involvement of the tumor microenvironment [2]. The long-standing standard of therapy for metastatic prostate cancer is androgen deprivation [4]. Aside from androgen deprivation therapy (ADT), which is the cornerstone of metastatic prostate cancer care, therapeutic options mostly consist of either innovative hormonal therapies (abiraterone, enzalutamide, and apalutamide) or taxane-based chemotherapy (docetaxel and cabazitaxel) [5,6]. Cabazitaxel, abiraterone, enzalutamide, sipuleucel-T, and the bone-specific radionuclide radium-223 represent all therapy possibilities for individuals with metastatic CRPC (mCRPC). These treatments are not curative and may have a low tolerability [7]
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