Ravi Madan, MD, on PSMA-PET in Recurrent Prostate Cancer – Medpage Today

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Prostate-specific membrane antigen positron emission tomography (PSMA-PET) promises to improve treatment of patients with recurrent prostate cancer. For now, however, this new technology, like prostate-specific (PSA) before it, could lead to substantial overtreatment of patients with recurrent disease. That is the warning from the authors of a “Comments and Controversies” article in the Journal of Clinical Oncology.
PSMA-PET imaging is superior to its predecessors, but the ability to detect smaller amounts of disease is not necessarily a game changer for recurrent cancer, noted Ravi Madan, MD, of the National Cancer Institute, and colleagues. “This imaging strategy is indeed revolutionary and will change how we see prostate cancer. The question is, should it change how we treat recurrent prostate cancer? … Now that PSMA-based imaging technology will unveil metastatic disease earlier, what will it reveal about our capability to be judicious in how we treat recurrent prostate cancer?”
In the following interview, Madan, a senior clinician in the NCI’s Genitourinary Malignancies Branch, Center for Cancer Research, and program director of the Physician-Scientist Early Investigator Program, discussed these issues in more depth.
You said that PSA is both a blessing and a curse for prostate cancer. Why is that?
Madan: PSA is a blessing in that it can be used to successfully screen patients for prostate cancer and also be used to detect recurrent disease. While this is beneficial for many patients, it can also lead to overtreatment in many other patients. In this way it is potentially similar to how PSMA imaging could be used in recurrent prostate cancer.
Although clinical trial data are lacking, there have been prospective studies evaluating PSMA-PET directed therapy. What have these studies told us?
Madan: One key finding in the PSMA-directed therapy studies of recurrent prostate cancer with the longest follow-up is that such approaches are likely not curative. This is likely because PSMA imaging does not detect all the recurrent disease in most patients. That said, there is data suggesting that patients with minimal disease — perhaps three lesions or less — may benefit from PSMA-directed therapy in terms of extending progression-free survival.
Data on the natural history of PSMA-PET positive disease is lacking. There is, however, natural history data on biochemically recurrent disease from Johns Hopkins. What does this data demonstrate, and how can it help fill the gap?
Madan: This data is invaluable in evaluating patients with recurrent prostate cancer. This data indicates that PSA doubling time may be an important way to risk-stratify patients who likely would have findings on PSMA imaging, but negative CT and Tc99 scans. Patients with PSA doubling times beyond 6 months may have a median metastatic progression-free survival (on CT or Tc99 bone scan) of 5 years or more.
For patients with longer/more favorable doubling times, metastasis may not develop for nearly a decade. Metastasis on CT and Tc99 are key indicators, because that is when ADT [androgen-deprivation therapy]-based treatment has been shown to improve survival, whereas no such data exists with PSMA imaging in recurrent disease.
What are one or two of the key outstanding questions that need to be answered to define the role of PSMA imaging in recurrent prostate cancer?
Madan: There are many important questions, some of which we hope to answer with a natural history study expected to open at the National Cancer Institute in the coming months. Among these questions are what is the natural history of disease progression on PSMA imaging and how does that relate to development of metastatic disease as defined in the conventional sense on CT and Tc99 bone scan? In addition, how do these changes relate to PSA changes and PSA doubling time?
But perhaps the key overarching question is, what is the best way to risk-stratify recurrent prostate cancer patients with findings on PSMA imaging in terms of therapeutic intervention and quality of life.
Read the article here.
Madan reported relationships with Pfizer, Boehringer Ingelheim, Janssen, and Bayer.
Primary Source
Journal of Clinical Oncology
Source Reference: Madan RA, et al “With new technology comes great responsibility: Prostate-specific membrane antigen imaging in recurrent prostate cancer” J Clin Oncol 2022; 40: 3015-3019.
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