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2025 National Institutes of Health – PCF Young Investigator Award

177Lu-PSMA-617 in PSMA PET(+) Biochemically Recurrent Prostate Cancer

Melissa Abel, MD      
National Institutes of Health   

Mentors: Ravi Madan, Peter Choyke

Description:

  • Nearly 30,000-50,000 men who are diagnosed each year with prostate cancer will ultimately develop biochemically recurrent prostate cancer (BCR; an early recurrent disease state in which PSA levels are rising but tumors cannot yet be detected on conventional CT or bone scans).  These patients commonly undergo observation or receive androgen receptor targeted therapies, but many ultimately progress to develop metastatic castration resistant prostate cancer (mCRPC), the lethal state of this disease. Effective new treatment strategies are needed, to avoid or delay the onset of mCRPC.
  • 177Lu-PSMA-617 (Pluvicto®) has demonstrated the ability to improve survival in men with prostate specific membrane antigen (PSMA) PET+ mCRPC. Whether this treatment can have a greater effect when administered earlier in the disease process, such as in patients with BCR, is unclear. 
  • Dr. Melissa Abel and colleagues are conducting a clinical trial to determine the benefits of 177Lu-PSMA-617 therapy in patients with micro-metastatic disease which can only be seen by PSMA PET imaging (but not on conventional scans). This trial is testing intermittent dosing of short-course 177Lu-PSMA-617 therapy, to determine optimal treatment dosing strategies to maximize benefits and minimize toxicities in patients with BCR.
  • Dr. Abel hypothesizes that patients with BCR may derive clinical benefit from intermittent dosing of 177Lu-PSMA-617, given the relatively low burden of disease at this stage, and that this approach could improve treatment tolerability while achieving disease control. 
  • This project will investigate the efficacy of intermittent doses of 177Lu-PSMA-617 for the treatment of PSMA+ BCR prostate cancer, and the dosimetry of 177Lu-PSMA-617 at different dose levels in tumor and salivary glands in relationship to treatment dose levels. In addition, Dr. Abel will analyze immune responses in blood at baseline and after 177Lu-PSMA-617 to identify immune changes and determine optimal immune combinations beyond immune checkpoint inhibitors for future investigations.
  • The results of this study may identify 177Lu-PSMA-617 as a possible alternative to anti-androgen therapy in BCR and improve cancer control at an earlier stage of disease, leading to a new treatment option for these patients.

What this means to patients: Patients with prostate cancer who develop biochemical recurrence (BCR) after primary tumor treatment commonly go on to develop lethal metastatic disease despite treatment with androgen receptor targeted therapies. Dr. Abel and colleagues are conducting a clinical trial that will determine the efficacy of 177Lu-PSMA-617 in patients with BCR, and are testing alternative dosing strategies with the goal to minimize toxicity. This may lead to a new and more effective treatment to prevent or delay progression to lethal, metastatic prostate cancer.