Evolving Metastatic PC Care: Integrating New Therapies, PSA Management, and Molecular Analysis

A roundtable discussion, moderated by Jigarkumar Parikh, MD, MBBS, highlighted the evolving landscape of prostate cancer treatment through the integration of multi-specialty collaboration, the introduction of new therapies and their challenges, and the crucial role of molecular and genetic testing in personalizing patient care and improving long-term outcomes. Dr. Parikh was joined by Joshua Perkel, MD; Rajesh Laungani, MD; Joseph Bear, MD; and Marc Greenstein, DO.

In the final segment of the roundtable series, the panel concludes with thoughts on the evolving landscape of prostate cancer treatment, focusing on the integration of new therapies, the importance of multidisciplinary collaboration, and the value of molecular analysis for personalized patient care.

View the previous segment of the roundtable series: Navigating mHSPC: Diagnostic and Imaging Strategies in Modern Practice.

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Dr. Parikh: Returning to our initial discussion about the integration of this drug and multi-specialty collaboration, I believe this approach will become increasingly prevalent as nuclear medicine and nuclear physicists become involved, especially with the use of lutetium. This trend will likely continue, necessitating the involvement of various specialties in patient care. Do you have any additional thoughts on how new drugs will be sequenced?

Dr. Bear: Returning to PSMA and scenarios where patients fail triple-line therapy, options like Pluvicto offer a sense of hope with new technology. There will be cost considerations and insurance coverage issues, but advancements in prostate cancer research with new lines of therapy, including potential monotherapy, provide optimism. Even if patients fail other lines of therapy, having positive PSMA PET results could lead to the use of radio-therapeutic treatments as the next step. I currently have two or three patients involved in these trials, though I am unsure if they are receiving the actual treatment or a placebo. This represents an exciting development for the community.

Dr. Laungani: An important point is understanding the significance of PSA levels. Patients often become fixated on this number, eagerly awaiting updates every three to six months. With many treatments, the PSA levels may fluctuate, and it can be challenging to explain that these changes do not always reflect the effectiveness of the treatment. We use various endpoints, including bone scans and PSMA, but the challenge remains in communicating to patients that a slightly higher PSA does not necessarily indicate worse outcomes.

Dr. Perkel: I use the concept of PSA doubling time to help patients understand their situation. It usually takes three or four visits to illustrate that a PSA increase from 3 to 3.5 over two years is not concerning. It is only when the PSA reaches 6 that there is a more significant issue. Explaining this helps patients focus less on minor fluctuations and more on overall trends. This is particularly challenging for patients who have had prostatectomy or radiation and are accustomed to very low PSA levels.

I also want to highlight the role of molecular analysis in oncology practices. Targeted therapies are increasingly used across various cancers, including prostate cancer. Performing molecular analysis on metastatic patients is now standard practice. Ideally, this is done on a biopsy sample, but if a patient had a prostatectomy years ago and lacks a new sample, we can use blood samples for genetic testing. Circulating tumor DNA can help identify mutations in tumor cells, potentially offering new treatment options.

Dr. Laungani: Even with BRCA1.

Dr. Parikh: Yes, BRCA1 and BRCA2, as well as HRD, which are relevant for PARP inhibitors. Immunotherapy remains an option, though it has been less effective in prostate cancer compared to other cancers. However, some patients with MSI-high tumors may still benefit from immunotherapy. Therefore, molecular analysis is crucial for identifying appropriate treatments.

Dr. Greenstein: This relates to Dr. Perkel’s point about patients focusing on numbers. Providing more data, such as PSA levels, germline tests, somatic tests, and PSMA results, helps patients understand their condition. I now conduct germline testing earlier to show patients, for example, that they are not BRCA positive, which is a positive indicator. Offering comprehensive data helps patients and their families understand the long-term outlook, potentially covering the next 5, 10, or even 15 years.

Dr. Bear: This approach is also valuable for understanding family history. For example, if a male patient’s father and grandfather had prostate cancer and he has sons aged 45 and 50, early testing can help identify risks. Detecting prostate cancer earlier in the next generation can be beneficial if there is a positive family history.