Prostate cancer is the most common cancer in men throughout the United States. Most men do not realize they have cancer due to its slow growing nature and reduced symptoms. Increased risk factors associated with prostate cancer include individuals older than 65, African American, and a history of cancer. While early stage is easily treatable, it often goes unrecognized until the tumor has advanced and metastasized to the bone and other tissues. As the tumor progresses, symptoms such as frequent urination, blood in urine and semen, erectile dysfunction, and back pain indicate a possible cancer diagnosis. Prostate cancer commonly spreads to the lymph nodes, bone, lungs, and liver. Current treatment options surgery, radiation therapy, hormone therapy, and chemotherapy. Combination strategies are also being used to optimize tumor reduction. Unfortunately, once the tumor spreads, the survival rate significantly decreases. Prostate tumor cells can also overcome therapeutic approaches, particularly hormone therapy, which also limits therapeutic opportunity.
Clinicians have begun using immunotherapy to better target prostate cancer. Specifically, checkpoint inhibitors, which activate immune cells, and vaccines have all been implicated as treatment strategies in prostate cancer patients. A recent paper in Cell Reports Medicine, by Dr. Matthew Dallos and others, demonstrated that combination immunotherapy with standard hormone therapy administered prior to tumor resection overcomes early-stage prostate cancer. This discovery is necessary to improve treatment for prostate cancer and prevent further progression. This combination therapy was found to overcome suppressive mechanisms in the tumor microenvironment that help tumors evade immune detection. Dallos is a Genitourinary (GU) Medical Oncologist at Memorial Sloan Kettering Cancer Center. His research focuses on prostate cancer and how to optimize treatment in patients.
Standard hormone replacement therapy (HRT) for prostate cancer is referred to as androgen deprivation therapy (ADT). Initially, this therapy drives immune cell infiltration in the tumor, which elicits anti-tumor efficacy. However, this response is quickly suppressed by other cells that are generated in response to ADT. To overcome ADT-resistance, Dallos and his team ran the first clinical trial in which immunotherapy was added to the ADT treatment regimen before tumor resection. The team focused on patients that did not have metastatic disease in other sites of the body. Each patient had early-stage tumor progression and had the possibility of being cured.
The study enrolled 24 men with high-risk prostate cancer and treated them with ADT and a checkpoint inhibitor. While ADT starves cells of testosterone to sensitize solid tumors to immune cells, the checkpoint inhibitor activates endogenous immune cells around the tumor to boost anti-tumor immunity. Checkpoint inhibitor therapy also depleted pro-tumor immune cells that were found to promote tumor progression. Therapeutic treatment prior to surgery allowed surgeons to resect most or all of the tumor. The ability to resect more tumor also gave scientists the opportunity to analyze deep tumor tissue previously unexplored. This provides insight into the immune milieu throughout the tumor and how to better develop therapies in the future. Furthermore, scientists hope to gain new clues about tumor cells signature patterns after treatment and identify biomarkers for future therapeutic evaluation. Overall, this work will provide feasibility for a new combination therapy in patients with early-stage prostate cancer.
Paper, Cell Reports Medicine, Matthew Dallos, Memorial Sloan Kettering Cancer Center
