Immunotherapy in Prostate Cancer: Successes, Failures, and Hopes for the Future

Prostate cancer is a serious health problem affecting millions of men worldwide. In 2020, an estimated 1.41 million new cases and 375 thousand prostate cancer-related deaths occurred globally. It is the second most common cancer in men after lung cancer, accounting for 14.1% of newly diagnosed male cancers worldwide. It is the most frequently diagnosed cancer in men in 112 countries.

Prostate cancer can be cured when detected early, and even advanced disease can respond well to treatment, with many options available. Tumor growth may range from very slow to moderate, and some patients survive for a long time even after metastasis. For example, among men diagnosed with local or regional prostate cancer in the United States during 2013-2019, 5-year survival exceeded 99%, compared with 34% in those with distant metastases. Across all stages, survival was 97%. Treatment may vary according to age and other existing health problems.

Options include surgery, radiotherapy, nonsurgical minimally invasive procedures, male hormone suppression, chemotherapy, and molecular treatments. However, as in many other cancers, immunotherapy has not yet become a standard prostate cancer treatment. Approved options remain limited, particularly in advanced disease, increasing the need for more effective, innovative approaches.

Immunotherapy in Prostate Cancer

Obtaining greater benefits from immunotherapy in prostate cancer may depend on identifying the patients most likely to benefit .

Immunotherapy has transformed treatment for some cancers but has generally not achieved the same success in prostate cancer. Although sipuleucel-T and pembrolizumab have shown some activity, immunotherapies overall have not delivered meaningful clinical benefits in this patient group.

One reason is that the prostate cancer microenvironment is considered an “immune desert.” Natural activation of the immune system is very limited in prostate cancer. T cells are generally absent from tumor tissue. There are many reasons, but one of the most important is the presence of immunosuppressive components within the tumor, such as tumor-associated macrophages and suppressor cells.

Another challenge is identifying the patients most likely to respond. In other cancers, histology and molecular biomarkers guide treatment selection, whereas prostate cancer immunotherapy studies have generally included an unselected group of patients with metastatic castration-resistant prostate cancer (mCRPC). Identifying which subgroups truly benefit, however, could allow greater gains from immunotherapy.

Despite these challenges, I believe innovations in immunotherapy will produce effective results in the future. Promising approaches include cellular treatments such as CAR T-cell therapy , BiTEs (bispecific T-cell engagers), and combinations of immunotherapies with chemotherapy, hormone therapy, or other treatments.

Current Treatment Options

The United States Food and Drug Administration (FDA) approved the first prostate cancer immunotherapy in 2010. Sipuleucel-T, an autologous dendritic cell vaccine , is approved for patients with metastatic castration-resistant prostate cancer (mCRPC) who are asymptomatic or minimally symptomatic.

In one study, this vaccine extended median overall survival by 4.1 months but had no significant effect on PSA levels or time to progression. Adverse effects are mild, treatment is completed in only one month, and it does not exclude patients from other clinical trials.

The FDA has also approved pembrolizumab for some patients with prostate cancer and high tumor mutational burden (TMB-H) . However, only 3% to 5% of patients with mCRPC meet these criteria, and only some respond favorably to pembrolizumab.

Immune Checkpoint Inhibitors

In addition to pembrolizumab, other drugs such as nivolumab, ipilimumab, atezolizumab, durvalumab, and avelumab from the class of immune checkpoint inhibitors are being investigated in prostate cancer. Studies have examined their effectiveness alone or in combination with other treatments. In most cases, however, the expected benefits have not materialized.

Treatment Outcomes

Responses to immunotherapy vary between individuals. Some patients respond favorably, while others experience more pronounced adverse effects. Identifying the patients most likely to benefit is important for achieving future success with immunotherapy.

BiTEs, Cellular Therapies, and Vaccines

BiTE (Bispecific T-cell Engager) therapies are a new generation of cancer immunotherapies. They contain bispecific antibodies recognizing two different targets: a particular antigen on cancer cells, such as PSMA, and a receptor on immune cells, such as CD3. BiTE molecules thus connect T cells to cancer cells, activating the immune system and targeting the cancer.

FDA-Approved BiTE Therapies: The best-known FDA-approved BiTE therapy currently is blinatumomab. Blinatumomab is used to treat acute lymphoblastic leukemia (ALL) and aims to destroy cancer cells by directing T cells toward them.

Alongside immune checkpoint inhibitors, BiTEs, CAR T-cell therapies, and dendritic cell vaccines are being investigated in prostate cancer. Although BiTEs do not completely remove immunosuppressive components, they may partially activate the immune response. However, these treatments can cause serious adverse effects.

Like BiTEs, dendritic cell vaccines have not provided consistent benefits in prostate cancer. However, newer approaches such as SYNC-T have shown promising results in small studies.

CAR T-cell therapies have shown low response rates in patients with prostate cancer. Studies targeting cell-surface antigens such as PSMA are ongoing, however, and promising results are anticipated.

In conclusion, I believe immunotherapy research in prostate cancer will progress. New-generation genetic analyses may help identify the patient groups most likely to respond, while combinations of immunotherapies and other treatments may accelerate advances. I am particularly hopeful about cellular therapies; with the right targets and engineering techniques, I believe we will develop treatments that can produce lasting remission.