Jacob Berchuck, MD, Genitourinary Medical Oncologist, Dana-Farber Cancer Institute, Instructor in Medicine, Harvard Medical School, discusses a recent study, Clinical considerations for the management of androgen indifferent prostate cancer. This is the conclusion of a two-part interview.

GU Oncology Now: Please discuss the significance of the recent FDA news granting a breakthrough therapy designation to LuPSMA for the treatment of patients with MCRPC.

Dr. Berchuck: Prostate specific membrane antigen, or PSMA, is a transmembrane protein that’s highly expressed in metastatic castration resistant prostate cancer. And Lutetium PSMA is a radioligand that delivers a beta radiation particle to PSMA expressing prostate cancer cells and the surrounding tumor microenvironment. The VISION trial was a recent Phase III randomized study that was presented earlier this month at ASCO, and published in the New England Journal of Medicine, of men who had received at least one prior antigen receptor signaling inhibitor, and one or two Taxane chemotherapies, who were randomized to standard of care treatment, or the addition of Lutetium PSMA.

One important point is that men eligible for the study had to have a Gallium PSMA PET scan with a positive PSMA, a positive lesion on PSMA PET, and no negative lesions on PSMA PET. And this accounted for about 86% of the men who underwent a Gallium PSMA PET scan in this study.

Excitingly, the study met the co-primary end points of prolonging the median radiographic progression-free survival by a little over five months, and prolonging the overall survival by four months. This is huge for our patients with advanced prostate cancer. These are men who are refractory to chemotherapy, refractory to hormone therapy, and really don’t have many great standard of care options left. So this is a huge unmet clinical need. And now that we have Lutetium PSMA as an additional life-prolonging therapy for these men is huge.

And finally, I just want to mention, there are several ongoing clinical trials looking at Lutetium PSMA and other disease settings in oligometastatic prostate cancer, metastatic hormone sensitive prostate cancer, and in combination with chemotherapy or immunotherapy. And so I think it’s going to be really interesting to see down the road, how we ended up using Lutetium PSMA to derive the most benefit for men with prostate cancer.

Can you discuss the molecular imaging tools that are promising for detecting prostate cancer in clinical practice?

This is a really exciting area. I think molecular imaging tools have the potential to transform how we diagnose and treat men with prostate cancer. And generally speaking, there are two types of molecular imaging, there is metabolic agents and receptor targeting agents. The most commonly used metabolic agents in prostate cancer are Fluciclovine PET and Choline PET.

The new kid on the block is Gallium PSMA PET. This recently received FDA approval in December, 2020, and targets the transmembrane PSMA protein, which is highly expressed in prostate cancer cells.

These molecular imaging tools have several potential uses across the prostate cancer disease spectrum. In men with localized, or clinically localized, prostate cancer, based on conventional imaging, you could imagine using these molecular imaging tools for section of a cold metastatic disease. Likewise for early detection of metastatic disease in men with biochemical recurrence, following definitive local therapy.

These molecular imaging studies clearly demonstrate a greater ability than conventional CT or bone scan for detecting a metastatic disease and men with prostate cancer. But I would caution that, we don’t have long-term data yet to guide how we should change management, based on findings on these molecular imaging studies. This is going to be a huge area of interest for the field over the coming years, and I think will ultimately transform how we treat men with certain stages of prostate cancer.

In the metastatic setting, as I mentioned, we now know that men with Gallium PSMA, PET positive disease, that the addition of Lutetium PSMA prolonged survival. But beyond that, I think in the metastatic setting, I think these molecular imaging studies could really help us develop a more nuanced understanding of advanced prostate cancer subtypes and guide precision medicine.

We now know from the VISION trial that 14% of men with advanced prostate cancer have PSMA PET negative disease. And there’s data that tumors that have low or absent expression of PSMA, or have greater expression of genes associated with a neuroendocrine prostate cancer. So I think, these observations raised some really interesting questions, specifically for the PSMA PET negative cohort of advanced prostate cancer. I imagine over the coming years, we’re going to have integrated analyses of molecular imaging with tumor molecular profiling, that will be really informative and hopefully advance precision medicine, and improve how we care for men with advanced prostate cancer.