Written by: Beth Dougherty
Medically Reviewed By: Atish Choudhury, MD, PhD, Toni Choueiri, MD, and Mark Pomerantz, MD

Dana-Farber’s genitourinary cancer team is devoted to research that will advance patient care and improve patient’s lives. Recently, that research — all of it years in the making — has paid off with major achievements. 

This includes: 

• Advances in clinical practice for patients with kidney cancer and prostate cancer. 
• Advances in precision diagnostics using liquid biopsies for prostate cancer. 
• Promising early results for innovative therapies such as personal cancer vaccines for kidney cancer and targeted medicines for metastatic bladder cancer. 
• Progress toward the discovery of targeted therapeutics for a rare form of kidney cancer. 

“We are constantly striving to improve the treatment and diagnosis of genitourinary cancers,” says Toni Choueiri, MD, director of the Lank Center for Genitourinary Oncology. “Our focused efforts are yielding results that are helping patients today and guiding our research towards more advances in the future.” 

Practice-changing results in kidney cancer and prostate cancer 

Dana-Farber research into the treatment of clear cell renal cell carcinoma, the most common type of kidney cancer, have led to practice-changing findings.

For the first time in fifty years, results from a phase 3 randomized, placebo-controlled trial have shown an overall survival benefit from a medicine provided after surgery to remove the cancer. Treatment with pembrolizumab, an immunotherapy drug, after surgery significantly prolonged overall survival in patients with clear cell renal cell carcinoma (ccRCC) at high risk for recurrence, according to an analysis of results from the KEYNOTE-564 study, led by Choueiri. 

We can now tell our patients that pembrolizumab after surgery not only delays recurrences but also helps them live longer,” says Choueiri. 

For patients with advanced clear cell renal cell carcinoma, a new medicine called belzutifan is available to reduce the risk of progression after surgery. In a phase 3 clinical trial led by Choueiri, belzutifan reduced the risk of progression 25% compared to everolimus in patients previously treated with immune checkpoint inhibitors and anti-angiogenic therapies. Based on this data, the drug was approved by the U.S. Food and Drug Administration in 2024.  

Belzutifan is a HIF-2 alpha inhibitor. When overabundant in cells, HIF-2 alpha is associated with increased cancer-driving activity, such as cell proliferation, immune evasion, low oxygen levels, and blood vessel formation. Dana-Farber’s William G. Kaelin, Jr., MD, was awarded a Nobel Prize in Physiology or Medicine in 2019 for the discovery of the role HIF-2 alpha in cancer and other diseases. 

Innovative therapies such as radioligand therapies are also being considered as standard treatment options for a wider group of patients with metastatic castration-resistant prostate cancer. 

In 2024, results of an additional analysis of data from a clinical trial called PSMAfore, led by Xiao X. Wei, MD, supported considering a radioligand therapy called ¹⁷⁷Lu-PSMA-617 as a standard treatment approach for patients with metastatic castration-resistant prostate cancer who have progressed on an androgen inhibitor but have not received taxane chemotherapy. The results consistently favored ¹⁷⁷Lu-PSMA-617 over a change to a different androgen receptor pathway inhibitor. 

In 2022, the FDA approved the radioligand therapy, a medicine that delivers tiny radioactive particles directly into the cancer, for patients with metastatic castration-resistant prostate cancer who had progressed after androgen receptor pathway inhibition and chemotherapy based on the PSMAfore trial results. This follow on analysis suggests the medicine could be used prior to chemotherapy and in lieu of a different androgen receptor pathway inhibitor. 

Intensified therapies could benefit patients with metastatic hormone-sensitive prostate cancer at the time of diagnosis and provide long-term remissions. 

Praful Ravi, MB, BChir, MRCP, and Atish Choudhury, MD, PhD, led an investigation of an approach called “total therapy,” which includes a combination of androgen deprivation therapy with or without an androgen receptor pathway inhibitor plus radiation to all sites of the disease. The idea was to determine if this intensified therapy could help patients who have been diagnosed with hormone sensitive prostate cancer that has spread only to a limited number of sites in the body, a disease state called oligometastatic hormone-sensitive prostate cancer. They found that 45% of patients who received total therapy remained progression free for three years after completing the therapy. 

Personalizing prostate cancer treatment 

Novel precision diagnostics could guide clinical decisions.

Himisha Beltran, MD, developed a blood test called NEMO that can reliably detect the emergence of neuroendocrine prostate cancer (NEPC), a form of prostate cancer that resists treatment with androgen therapy. The blood test can differentiate NEPC from castration-resistant prostate cancer adenocarcinoma (CRPC-adeno). Differentiating NEPC from CRPC-adeno using a blood test gives physicians a non-invasive and reliable way to assess disease burden and monitor patients for resistance to therapy. 

The blood test uses fragments of DNA in the blood stream, called cell-free DNA, to detect specific epigenetic changes, in the form of DNA methylation markers that switch genes on and off, to distinguish CRPC-adeno from NEPC.

“Now that we have robustly shown the accuracy of this panel test, we’re excited to apply it to clinical questions,” says Beltran. “We’d like to determine if this test can help us predict which patients respond to certain prostate cancer treatments, including precise treatments that target neuroendocrine prostate cancer.”

Understanding inherited risk of prostate cancer helps guide treatment and screening.

It is known that certain BRCA2 mutations can increase the risk of developing aggressive prostate cancer. In new research, Mark Pomerantz, MD, has found that prostate cancer patients with a BRCA2 mutation may not face a substantially worse prognosis compared to those who do not have a BRCA2 mutation. The study also suggests that information about inherited risk genes can help guide treatment. Patients with BRCA2 mutations respond favorably to platinum chemotherapy and drugs called PARP inhibitors. The study raises the possibility that BRCA2 carriers may have a better prognosis than other high-risk patients if they receive one of these medicines upfront. This hypothesis is now being tested in a prospective clinical trial. Further, it is helpful for people with a family history of cancer to determine if they carry an inherited genetic risk for cancer and would benefit from prostate cancer screening to help identify the cancer early when it is easier to treat.  

Leading edge research in kidney cancer and bladder cancer 

A collaborative team of Dana-Farber investigators has reported positive results of an early phase clinical trial of a NeoVax personalized cancer vaccine for kidney cancer after surgery to remove the cancer.

In a phase 1 clinical trial led by Choueiri and cancer vaccine experts Catherine Wu, MD, and Patrick Ott, MD, PhD, the investigators reported that nine of the nine patients in the trial, all with stage III or IV clear cell renal cell carcinoma, generated a successful anti-cancer immune response after initiation of vaccination with the NeoVax personalized cancer vaccine. The vaccines were administered after surgery to remove the tumor and are designed to train the body’s immune system to recognize and eliminate any remaining tumor cells. At the time of data cut-off (median of 34.7 months), all patients remained cancer-free. 

“We’re very excited about these results,” says Choueiri.

Patients with a form of metastatic bladder cancer called metastatic urothelial carcinoma have few options, but Dana-Farber research suggests an innovative treatment approach is worthy of further investigation. 

Joaquim Bellmunt, MD, PhD, investigated a targeted medicine called sapanisertib in a phase II study in patients with metastatic urothelial carcinoma. Sapanisertib is a dual-acting inhibitor of the mTOR pathway, a well-known pathway and target of many cancers.

The study was interrupted by the COVID-19 pandemic, but Bellmunt and colleagues observed that sapanisertib in combination with paclitaxel chemotherapy showed clinical activity in patients who had previously received many different treatments. These results suggest that more clinical research is warranted. 

Dana-Farber experts are making progress toward finding new therapies for a rare form of kidney cancer: 

Chromophobe (Ch) renal cell carcinoma is a rare form of kidney cancer accounting for roughly 5% of renal cell carcinoma (RCC) cases. Advances in treatment have been significant for clear cell RCC, but not for chromophobe RCC, which is treated with surgery and has no approved targeted therapies. But at Dana-Farber, Elizabeth Henske, MD, has uncovered vulnerabilities in chromophobe RCC that could lead to the discovery of new therapies for the disease. She received the Kidney Cancer Research Alliance (KCCure) award in 2023 and 2024 supporting her research.