Treatment and Management of Patients With Prostate Cancer
The following is a lightly edited manuscript of a teleconference discussion on treating patients with localized prostate cancer in the VHA.
So, we are biopsying patients’ tumors, looking at the mutations in their germline DNA, and matching patients to treatments and vice versa. The DNA repair defects is the one that’s probably under most active evaluation right now. Another example of a biomarker is the AR-V7, which is a mutation in the androgen receptor that renders the cancer resistant to enzalutamide and abiraterone.
Also, I have a study of pembrolizumab which is a PD-1 inhibitor, and I’ve seen some very good responses to that therapy. And we’re not yet sure how to identify prospectively those patients who are likely to respond.
Use of Imaging
Dr. Nickols. The sensitivity of technetium-99m bone scans and CT (computed tomography) scans is not good enough. Many patients that we classify as M0, but with clear evidence of disease with a rising PSA, will be more accurately classified as M1 when the imaging allows this to be the case.
I think prostate-specific membrane antigen positron emission tomography (PET), which is not approved at this time, is going to be of value. A lot of data are coming out of Europe and in the recurrence setting show that PET imaging can detect metastatic sites at PSA values as low as 0.2 with the per lesion sensitivity around 80% and a specificity upward of 97%. This is clearly far and away much better than anything we have now.
There’s going to be a whole cohort of patients that we literally can’t see now, patients with essentially minimally metastatic disease, and they will be revealed when the imaging gets there. And the question is what to do for these patients. Treating patients with a heavy metastatic disease burden is much different from treating patients who may have just one or a few areas of disease outside of their prostate. And we need new strategies for these patients. We are now looking at new treatment regimens for patients with limited metastatic disease burden. I think this is going to be important going forward.
It’s also worth asking: What is the role of local therapy in patients with advanced prostate cancer, patients with metastatic disease? If you look at the patients who were in a lot of the old trials, for example, the NCIC trial, that was adding radiation to hormone therapy for high-risk patients, about 25% of patients in that trial had a PSA > 50. That’s a lot. Many of those patients probably had occult metastases. And there are trials now looking at the role of local therapy in metastatic patients.
Another area of interest is precision oncology, which Dr. Graff touched on, is starting to play a big role in the metastatic setting, but what about the local setting? There are now genomic classifiers available to help with risk assessments, but we don’t yet have much in the way of predictive tools that help guide specific therapies in the localized setting. We know that patients, for example, who have germline BRCA1 or 2 mutations have a worse outcome, period, after local therapy; and right now it may play some into treatment decisions, but we don’t have tailored therapy yet in the localized setting at the molecular level. And I think this is something that we need to start looking at.
Dr. Aronson. The VA is a very rich environment for performing clinical research as well as translational research (bench to bedside). And for example, at the West Los Angeles VAMC, I think one of the key steps that we have taken, moving forward is now our urology, radiation oncology, and hematology-oncology research groups have now merged together. This allows us to not only combine our administrative resources but to really improve the ability for us to perform highquality research in our veterans. And so that’s a model which I think other VAs might consider pursuing, depending upon their circumstances.
Author Disclosures
Dr. Graff has received research support from Sanofi, Astellas, Merck, Janssen, and Bristol Myers Squibb; an honorarium from Astellas; travel support from Clovis and Sanofi; and has consulted for Bayer and Dendreon. No other authors report actual or potential conflicts of interest with regard to this article.
Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
