The Future of Metastatic Prostate Cancer ManagementJune 22, 2022
The management of advanced prostate cancer is rapidly evolving, and a few presentations at the recent American Urological Association (AUA) annual meeting addressed some of the exciting new developments that are on the horizon in the field.
In this exclusive MedPage Today video, Adam Kibel, MD, chief of urology at Brigham and Women’s Hospital and Dana-Farber/Brigham and Women’s Cancer Center in Boston, discusses some of the highlights of his presentation.
Following is a transcript of his remarks:
I gave two presentations. The second presentation was looking at both immunotherapy and the future in terms of our management of prostate cancer, in metastatic prostate cancer. It was a little bit of a grab bag of topics.
The immunotherapy one was very much focused on [sipuleucel-T (Provenge)], which is the only FDA approved immunotherapy for prostate cancer. Probably slightly underutilized in the United States. I spent a little time in the presentation talking about CAR T cells, which everybody is very excited about. But the take home message is that they’re not ready for prime time in prostate cancer yet. I just summed up about 5 minutes of a talk in one sentence.
They’re very exciting. My hope is that they will catch fire and they will dramatically change our management of cancer. They have the potential to essentially function as lifelong immunity against the cancer. It’s not really a vaccine. It’s manipulating your own immune system to recognize the cancer cell better, so the cancer cells are attacked.
I also spent some time talking about other forms of immunotherapy — specifically patients that have defects in mismatch repair enzymes can get [pembrolizumab (Keytruda)]. Pembro was FDA approved not for prostate cancer, but for tumors that have defects in mismatch repair.
And so particularly for the medical oncologist more than the urologists, I think it’s important to recognize that. Sequence the tumor, see if there are defects in mismatch repair, and if there are, or microsatellite instability, and if there are, they can get pembro.
I think we as urologists are often approached to be asked, does this make sense? So I think we need to be aware of it so that we can go ahead and counsel our patients correctly about whether it’s a good thing for them.
The two last parts of that grab bag topic, future directions, had to do with PARP inhibition. There’s a lot of interesting data now emerging about precision medicine in prostate cancer, and patients that have defects in DNA repair in general — specifically BRCA2 — appear to respond very well to PARP inhibition when they have metastatic disease.
And so again, at least in 2022, most urologists are referring to the medical oncologist, but I think an awareness that defects in DNA repair can allow our patients to get a very targeted therapy, which has clearly been shown to increase life expectancy and quality of life in men that have defects in these particular genes, is important for us to recognize.
And then the last thing that I covered in this potpourri was moving treatment earlier in the disease state. And I think that is very important for urologists to understand. For breast cancer, colon cancer, lung cancer, bladder cancer — pretty much any cancer you can think of — the paradigm is to treat patients systemically and to treat the local disease.
We all are aware of that in bladder cancer. You give MVAC chemotherapy or [gemcitabine/cisplatin] followed by a cystectomy. And maybe you might not decide to do it because of the potential toxicity, but we are all aware of the potential benefit there. Prostate cancer, we don’t have that.
The reason we don’t have that? No drugs worked until about 2004. Once we moved drugs from the very aggressive castrate-resistance state to the castrate-sensitive state, we saw an increase in life expectancy from 2-4 months to 12-24 months — and now 1-2 years. And the idea is that if we move that treatment even earlier, into the high-risk localized setting, we can improve cure rate. We can extend life by maybe one or two decades, which let’s face it, in a 78-year-old might be to the end of their life expectancy.
So the one, STAMPEDE, is recently a trial where they gave patients radiation therapy, abiraterone, and androgen-deprivation, compared to radiation therapy and androgen-deprivation alone, in patients that had very high-risk disease and found the patients that got the addition of the abiraterone lived longer.
Similar trials are being done for prostate cancer. Phase II data show that there is an excellent response and patients do appear to benefit. Randomized phase III trials are ongoing and are coming. There was one phase III randomized trial looking at docetaxel used with chemotherapy instead of hormone therapy. And it did not meet its primary endpoint. And there were a lot of side effects, so it hasn’t caught fire, but patients did appear to live longer that got the docetaxel. Maybe to the detriment of their quality of life.
I think most of us think that hormone therapy is gonna be a better way to go. But the bottom line is this is on the horizon. This is going to happen soon. And it needs to be part of our armamentarium of managing patients with high-risk localized prostate cancer.