Perspectives on Metastatic and Castration-Resistant Prostate Cancer: A Discussion with Ulka Vaishampayan, MD

Ulka Vaishampayan, MD.

Selma Khenissi, MPS: Hello, welcome to Oncology Data Advisor. I’m Selma Khenissi from i3 Health. In honor of prostate cancer awareness month, we are here today with Dr. Ulka Vaishampayan, who will be discussing issues surrounding prostate cancer. Welcome.

Ulka Vaishampayan, MD: Thank you for having me on this interview. I would like to bring our problems surrounding prostate cancer to the forefront today. Especially with this being Prostate Cancer Awareness Month, we should be thinking about the problem that faces us today. Men are still dying of advanced prostate cancer. This is a very common disease. One in four men, if they do screening, will be diagnosed with prostate cancer. We need to focus on the lethal types of prostate cancer and be able to differentiate which ones need active treatment, and if we can, expand and develop more and more new treatments that will help improve the quality of life and survivorship of these patients, as well as extend their life expectancy.

Selma Khenissi: In cases of prostate cancer, how common is castration-resistant prostate cancer?

Dr. Vaishampayan: Castration-resistant prostate cancer is one of the stages in the natural history of the disease. Upfront at diagnosis, the majority of the patients are diagnosed with localized disease. About 10% to 15% of the patients will be diagnosed with advanced or metastatic disease. After they are treated with androgen deprivation therapy or testosterone suppression therapy, if they start developing progression, then that is considered castrate-resistant prostate cancer. Almost everybody with metastatic disease, given enough time, on an average of about two years or so, will progress to develop castrate-resistant prostate cancer. Now, within the localized disease group, about a third of the patients will end up showing a relapse in their lifetime. Initially, again, the treatment is either local therapies or androgen deprivation therapy. Again, testosterone suppression treatment is one of the backbones of treatment for prostate cancer. After that, if the prostate-specific antigen (PSA) is continuing to rise, that part is considered non-metastatic castrate-resistant prostate cancer.

Within castration-resistant prostate cancer, there is a non-metastatic stage where you don’t have any obvious signs of spread of the cancer on the imaging that you use. Then there is metastatic castrate-resistant prostate cancer, which is where you’re already seeing signs of spread on imaging. Now, each of those states are sort of merging into each other because we are gradually getting better and better with our novel imaging techniques. For instance, prostate-specific membrane antigen-positron emission tomography (PSMA-PET) scans are increasing our sensitivity of detecting metastases earlier, even at lower levels of PSA. Early detection of metastases is happening more and more as we use some of these novel imaging techniques.

Selma Khenissi: Very comprehensive answer. Thank you so much, Dr. Vaishampayan. Why is it particularly challenging to treat metastatic castration-resistant prostate cancer?

Dr. Vaishampayan: The challenge with metastatic castrate-resistant prostate cancer is that it ends up being a heterogeneous disease. It’s also frequently a very symptomatic disease. Patients are not feeling good because of the cancer. The heterogeneity is because it’s no longer hormone-driven; or part of it may still be hormone-driven, but there are also androgen-resistant clones, which are now becoming more and more predominant. There may be a neuroendocrine component within the tumor. Unfortunately, as of now, we don’t have a good way to detect which kind of cancer it is, to be able to direct the treatment accordingly. There are definitely a number of techniques, both tissue-based DNA and RNA sequencing, that are available to look deeper into which target is really driving the disease at that point, and then to match the treatment exactly to that target. That is sort of the cutting-edge research being looked at in metastatic castrate-resistant prostate cancer. But as of now, it remains an incurable, almost terminal malignancy in the majority of patients.

Selma Khenissi: I see. So what treatments are on the horizon for metastatic castration-resistant prostate cancer?

Dr. Vaishampayan: The one closest to the horizon is a PSMA-based treatment. It’s a PSMA-based radiation, a small molecule that then attaches and releases radiation right at the cancer cell level. PSMA Lutetium 177 is that type of treatment. It’s a completely different mechanism of action than what we’ve had all this time. So far in prostate cancer, the approved metastatic castration-resistant prostate cancer treatments include hormonal therapy, immunotherapy, and chemotherapy. Now, we have this radiation-based treatment with PSMA targeting, which allows us to differentially treat the cancer and potentially not have as many side effects on normal tissue. This agent has already shown improvement in both progression-free survival and overall survival in a randomized trial that was reported and published in The New England Journal of Medicine this year. This agent is right now under consideration by the FDA for approval.

Selma Khenissi: That sounds promising. How are the new imaging methods incorporated into the management of metastatic prostate cancer?

Dr. Vaishampayan: Clearly, if you have a PSMA-targeted therapy, you would need to determine whether the tumor is expressing PSMA. The PSMA-PET scan does allow you to check for that. In the VISION trial, about 13% to 15% of the patients were not eligible because they did not express enough PSMA on their tumors. Based on that, I think that would be the first immediate use. Besides that, a lot of the novel imaging techniques, such as the fluorodeoxyglucose (F-18) PET scan, are very sensitive for bone metastases. That is something to consider.

Other imaging techniques, such as the the fluciclovine PET scan, are currently approved for PSA-relapsed prostate cancer. That is where you are looking into early detection of metastases. That way, if you find the diagnosis of an oligometastatic state, which is three or less sites of metastases, you could potentially do a focused radiation called stereotactic radiation therapy to those locations and continue without monitoring the patient with or without systemic therapy. That kind of strategy is currently being explored, and clinical trials are following up with these patients after oligometastatic disease to see if that is a strategy that improves lifespan and clearly delays a lot of the systemic therapy side effects.

Selma Khenissi: Awesome. So what is your advice to community oncologists treating patients with metastatic castration-resistant prostate cancer?

Dr. Vaishampayan: Evaluate the patient closely. This is not a disease where you can get measurable metastases. When bone is involved, it’s very hard to measure the tumors. You’re not going to get a measurement that will tell you clearly whether a patient is progressing. The art of medicine does become critical for metastatic prostate cancer, because you have to evaluate the patient for their symptoms. Think about neuroendocrine prostate cancer presentation, where the PSA may be undetectable or very low, but the patient overall is clinically not doing well or has visceral metastases. Also think of genomic sequencing early on for this patient population, because within either germline mutations or somatic mutations, if they have DNA repair mutations, you could potentially use poly adenosine diphosphate-ribose polymerase (PARP) inhibitors. This gives you an added therapeutic option for these patients. I would say, think about genomic sequencing, think about the heterogeneity of the cancer, and carefully sequence the different therapies that we have available.

Selma Khenissi: Thank you so much, Dr. Vaishampayan, for taking the time to speak with us today.

About Dr. Vaishampayan

Ulka Vaishampayan, MD, is a Professor of Internal Medicine and the Director of the Phase 1 Program at the University of Michigan Rogel Cancer Center. She is also the Chair of the SWOG Advanced Renal Committee, a member of the National Cancer Institute (NCI) Renal Task Force, and a board member of the Michigan Society of Hematology/Oncology. Dr. Vaishampayan specializes in the treatment of genitourinary malignancies, including prostate cancer, bladder cancer, and renal cell carcinoma, and her research focuses on translational drug development. She has authored or coauthored numerous publications in peer-reviewed journals.

For More Information

Sartor O, de Bono J, Chi KN, et al (2021). Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med, 385(12):1091-1103. DOI:10.1056/NEJMoa2107322

This transcript has been edited for clarity. Any views expressed above are the speaker’s own and do not necessarily reflect those of Oncology Data Advisor. 

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