Thousands of clinicians and researchers gathered in February for the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU). Held in San Francisco and online, the conference featured hundreds of studies of prostate cancer treatment, diagnosis, prevention, and survivorship—many led by researchers funded by PCF. For individuals with prostate cancer and their caregivers, here are five key takeaways from ASCO GU 2025.
Talazoparib May Benefit More Patients with mCRPC
Combining treatments may boost therapeutic response and help patients with cancer stay in remission longer. Clinical trials are done to check if new treatment combinations work and are tolerable.
The phase 3 TALAPRO-2 trial looked at the combination of talazoparib plus enzalutamide for the first-line treatment of metastatic castration-resistant prostate cancer (mCRPC), or cancer that has spread outside the prostate gland despite hormone therapy. Talazoparib is a type of medicine called a PARP inhibitor, while enzalutamide is an androgen receptor pathway inhibitor.
At ASCO GU, researchers from TALAPRO-2 reported that adding talazoparib to enzalutamide improved overall survival in patients with mCRPC, even if they did not have HRR gene alterations, which are known to predict a better response to PARP inhibitors.
In this study, combined treatment with talazoparib and enzalutamide increased overall survival by nearly 9 months compared with enzalutamide alone. Survival was best in study participants who had HRR alterations, but many who did not have these gene changes still benefitted from talazoparib. Although talazoparib caused more side effects, it helped patients go longer before their quality of life worsened. About one in five patients stopped taking talazoparib due to side effects.
PCF played a key role in developing PARP inhibitors such as talazoparib. A PCF-funded team showed that PARP proteins contribute to prostate cancer and that blocking them can help stop it from getting worse. The PCF-funded International Prostate Cancer Dream Team discovered that patients with advanced prostate cancer often have HRR gene alterations and led the first clinical trials of PARP inhibitors in prostate cancer.
Darolutamide Helps Patients with High-Volume and Low-Volume mHSPC
Metastatic hormone-sensitive prostate cancer (mHSPC) is prostate cancer that has spread outside the prostate but can be controlled with hormone therapy. Treatment options include either ADT plus an androgen receptor pathway inhibitor (ARPI), or “triple combinations” of ADT, docetaxel, and an ARPI like darolutamide.
The phase 3 ARANOTE trial looked at a chemotherapy-free regimen of ADT plus darolutamide for treating men with mHSPC. Researchers found that this combination reduced the risk of death or disease progression compared with ADT alone. Darolutamide also was linked to less fatigue and a lower risk of stopping treatment due to side effects.
At ASCO GU, ARANOTE researchers discussed darolutamide’s effectiveness depending on how much cancer patients had in their bodies. Adding darolutamide to ADT reduced the risk of death or disease progression by about 70% in patients with less cancer in their bodies (low-volume mHSPC) and by about 40% in patients with more cancer in their bodies (high-volume mHSPC).
Based on these findings, a chemotherapy-free combination of darolutamide and ADT may improve survival and quality of life in patients with either high or low-volume mHSPC, as compared with ADT alone. However, adding a third treatment may also make sense for some individuals with high-volume mHSPC, especially if prostate cancer has spread to their organs or if they have other risk factors for aggressive disease. Future research will shed more light on this approach.
PORTOS Score Helps Predict Who Needs Higher Doses of Radiation
Radiation can effectively treat prostate cancer, but it has side effects. For this reason, it’s important not to use a higher dose than needed.
The PORTOS score was designed to predict which patients with prostate cancer should receive stronger radiation and which will do just as well with a lower dose. PORTOS stands for Post-Operative Radiation Therapy Outcomes Score, and it looks at 24 genes in prostate cancer cells. It’s based on the Decipher test.
At ASCO GU, researchers reported that patients with prostate cancer who had higher PORTOS scores did better with stronger radiation therapy, while those with lower PORTOS scores did just as well with a lower dose of radiation. This was the case when radiation was the primary treatment and when it came after surgery (so-called “salvage” treatment).
Based on these studies, calculating the PORTOS score may help clinicians decide which individuals with prostate cancer should receive stronger radiation and which would do just as well with a lower dose, potentially avoiding unnecessary side effects.
PCF has provided critical funding for researchers who helped develop the PORTOS score. These include Dr. Shuang (George) Zhao of the University of Wisconsin-Madison, the late Dr. Felix Feng of the University of California, San Francisco, and Dr. Phuoc Tran of the University of Maryland, Baltimore.
PSMA PET Imaging Helps Patients in the Real World
PSMA PET is a special type of scan that may do a better job of finding prostate cancer than standard imaging tests. It was FDA-approved in 2020 and is being used more and more in the United States and elsewhere. At ASCO GU, several studies showed how PSMA PET can help patients in the real world (outside of clinical trials).
In one study, PSMA PET showed where prostate cancer was in the body in more than 70% of patients with biochemically recurrent prostate cancer (meaning their PSA went back up after prostate cancer treatment). Importantly, PSMA PET often was positive even when standard imaging tests were negative, and patients lived longer when clinicians changed treatment based on PSMA PET results. These findings suggest that earlier, customized treatment guided by PSMA PET imaging may improve survival. Ongoing clinical trials will help more clearly answer this question.
Another study looked at using PSMA PET imaging to help predict how long someone with prostate cancer will live. Researchers developed tools (called nomograms) that use PSMA PET results to predict survival. Across all stages of prostate cancer, the nomograms performed better than current methods. In the future, these tools may be useful for treatment planning.
PCF has funded over 90 studies of PSMA and PSMA PET imaging, including the first clinical trial in this setting. Studies funded by PCF were critical to the FDA approval of the first PSMA PET agents used for imaging in both newly diagnosed and recurrent prostate cancer.
Advances in Radioligand Therapy
Radioligand therapy uses radioactive drugs to precisely target prostate cancer cells. It has shown good results in patients whose prostate cancer has spread and is no longer responding to other treatments.
177Lu-PSMA-617 is a newer radioligand therapy approved for patients with mCRPC who have a positive PSMA PET scan and have already received an androgen receptor pathway inhibitor and taxane chemotherapy. At ASCO GU, researchers reported on a clinical trial of 177Lu-PSMA-617 plus enzalutamide in patients with high-risk mCRPC that had progressed on other treatments.
In the study, the combination improved overall survival by about 8 months compared with enzalutamide alone. Adding 177Lu-PSMA-617 to enzalutamide also was linked to better quality of life, better physical functioning, and less pain and fatigue.
Several other studies are examining treatment combinations with 177Lu-PSMA-617. This is a promising area where we can expect to see more results soon.
Researchers also are studying the use of radioligand therapies in community practice (outside the setting of clinical trials). In one small study of 177Lu-PSMA-617, treatment response was unrelated to location of cancer in the body except when patients had liver metastases.
In another small study, 88% of White patients and 81% of Black patients survived at least 12 months after 177Lu-PSMA-617 therapy. This study is important because race and ethnicity sometimes affect how people with cancer respond to treatment, but most participants in prostate cancer clinical trials—including trials of 177Lu-PSMA-617—have been White.
Studies like these will help clinicians understand which patients are most likely to benefit from 177Lu-PSMA-617, and how to improve the chances of a good treatment response for all patients.
Dozens more prostate cancer studies were reported at ASCO GU. Their diversity and quality highlights remarkable ongoing progress in the field. This momentum will continue with the support of visionary researchers, funders and patient advocates, including the entire PCF community.
