Abstract
In the last decade, immunotherapy has revolutionized the treatment landscape of several hematological and solid malignancies, reporting unprecedented response rates. Unfortunately, this is not the case for metastatic castration-resistant prostate cancer (mCRPC), as several phase I and II trials assessing programmed death receptor 1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitors have shown limited benefits. Moreover, despite sipuleucel-T representing the only cancer vaccine approved by the Food and Drug Administration (FDA) for mCRPC following the results of the IMPACT trial, the use of this agent is relatively limited in everyday clinical practice. The identification of specific histological and molecular biomarkers that could predict response to immunotherapy represents one of the current challenges, with an aim to detect subgroups of mCRPC patients who may benefit from immune checkpoint monoclonal antibodies as monotherapy or in combination with other anticancer agents. Several unanswered questions remain, including the following: is there—or will there ever be—a role for immunotherapy in prostate cancer? In this review, we aim at underlining the failures and promises of immunotherapy in prostate cancer, summarizing the current state of art regarding cancer vaccines and immune checkpoint monoclonal antibodies, and discussing future research directions in this immunologically “cold” malignancy.
Highlights
Prostate cancer (PC) is the most commonly diagnosed cancer in men, representing one of the leading causes of cancer-related death worldwide [1]
We summarize the current state of art regarding immunotherapy in PC, including biomarkers of response, cancer vaccines, chief trials on immune checkpoint monoclonal antibodies and novel immune-based combinations in this immunologically “cold” malignancy with many unanswered questions
Rather than a single biomarker, an approach based on the integration of different biomarkers could most likely help in improving the understanding of the role of immune checkpoint monoclonal antibodies in malignancies where immunotherapy has reported low overall response rate (ORR), such as metastatic castration-resistant prostate cancer (mCRPC)
Summary
Prostate cancer (PC) is the most commonly diagnosed cancer in men, representing one of the leading causes of cancer-related death worldwide [1]. Many patients affected by metastatic disease will develop metastatic castration resistant PC (mCRPC) [3]. Immune checkpoint monoclonal antibodies are not included among these drugs. Modern immunotherapy has revolutionized the management of a number of malignancies, immune checkpoint monoclonal antibodies are still looking for their niche in several tumors where these agents do not seem to provide ideal results in unselected patients—such as mCRPC [9]. We summarize the current state of art regarding immunotherapy in PC, including biomarkers of response, cancer vaccines, chief trials on immune checkpoint monoclonal antibodies and novel immune-based combinations in this immunologically “cold” malignancy with many unanswered questions. We performed a research on the clinicaltrials.gov database for recruiting and active, not recruiting, trials
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