Can intensive hormonal suppression before surgery prevent the recurrence of potentially aggressive prostate cancer?
My goal in writing about prostate cancer is to offer reassurance and hope, as well as a nudge or two when it’s time to take action. I’ve been very excited in previous posts to write about the wider cure window for oligometastases, getting cancer when it first escapes the prostate and is large enough to be seen on conventional imaging. Now, with PSMA-PET imaging, at the first sign of a rise in PSA after treatment, men can see where metastatic cancer may be hiding when it is too small to be detected by other imaging and seek further treatment earlier than ever. still hoping for a cure. But maybe we can be even more proactivelywhich brings us to the work of National Cancer Institute medical oncologist Fatima Karzai, MD. I interviewed her recently for the Prostate Cancer Foundation.
What does it take to ensure that identified high-risk prostate cancer never comes back? A new Phase II clinical trial aims to find out, and it’s notable in two ways: First, says Karzai, the study’s principal investigator, “We are aggressive.” And two, with the help of PSMA-PET imaging, researchers can observe the effects of anticancer drugs – three powerful forms of hormone therapy, in addition to surgery – on the cancer in real time.
Three steps beyond surgery: This is a no-holds-barred, all-out attack on localized prostate cancer that has the potential to be aggressive and recur after treatment.
Karzai and his colleagues take high-risk cancer – even though it is localized – very seriously, and rightly so: more than half of patients diagnosed with high-risk prostate cancer have a recurrence, sometimes years later, and more than 20 percent of men with high-risk prostate cancer die of their disease within 15 years. Note: these numbers do not yet cover the use of the PSMA-PET scan, which many doctors believe is a game changer.
What will a short course of triple hormone therapy do? Researchers hope that this systemic (body-wide) treatment before surgery will hit any stray cancer cells while they are most vulnerable and reduce the risk of full-blown metastases. A similar trial showed promising results after more than three years of follow-up.
The trial is still recruiting patients. So far, Karzai says, the average participant is in his mid-60s with a Gleason score of 8 or 9, but the trial is open to men of any age with high- or even average-risk prostate cancer that hasn’t spread in other parts of the body (up to stage N1 cancer) who are planning to be treated with a prostatectomy.
For six months before surgery, the men in the trial undergo “intense androgen deprivation therapy,” says Karzai, who serves as Clinical Chief and Director of Internal Medicine for the Cancer Research Center’s Genitourinary Malignancies Branch at the National Cancer Institute . This includes: Goserelin (Zoladex),which disrupts testosterone and two drugs that target the androgen receptor: abiraterone (given with prednisone) and enzalutamide. “We’re really reducing male hormones as low as we can.” The cancer is imaged with MRI and serial PSMA-PET scans—before treatment, two months after starting treatment, and again before surgery—and patients may be asked to have an additional prostate biopsy two months after the study .
Note: Testosterone loss is temporary! As patients recover from surgery, testosterone begins to return. “It takes six months to a year from the second shot (given in the middle of the study) and all patients will recover their testosterone. Their libido will be affected temporarily, but as they start to recover their testosterone, their libido will return.”
During the six months, “we see PSA levels become very low or undetectable,” says Karzai. She and her colleagues are also looking for corresponding changes in tissue (in biopsy samples and in prostate tissue itself after surgery), studying genetic mutations in cancer, and – for the first time – observing how the effects of intense hormone therapy play out in PSMA Imaging -PET. “We see some patients who are extremely sensitive to androgen deprivation and some who are not. the difference really has to do with the unique biology of their cancer.” In PSMA-PET, “usually what we see is that the area that lights up becomes less. In some patients with disease that’s quite aggressive, it won’t go away completely in six months,” but it’s decreasing. “We are not seeking to cure them completely with this treatment, but to take them to the operating room,” and lo to maximize their chances of recovery.
One goal of the study is to learn how to incorporate PSMA-PET scans into the treatment of men diagnosed with high-risk prostate cancer. “Right now, these men are not routinely getting PSMA-PET scans. We’re also trying to see, up front, if you’re doing more androgen suppression, what does that mean for the overall outcome?” Is it possible to hit aggressive cancer hard enough in the localized state that it won’t come back? “We will be following these patients for a long time.”
For more information about this study, please contact the study’s research nurse, Katherine O. Lee-Wisdom, RN at (240) 858-3525 or email: katherine.lee-wisdom@nih.gov.
Additionally with Book, I have written about this story and much more about prostate cancer on the Prostate Cancer Foundation website, pcf.org. The stories I have written are in the “Understanding Prostate Cancer” and “For Patients” categories. As Patrick Walsh and I have said for years in ours books, Knowledge is power: Saving your life can start with going to the doctor and knowing the right questions to ask. I hope all men put prostate cancer on their radar. Get a baseline PSA blood test in your early 40s and if you are of African descent or have a family history of cancer and/or prostate cancer, you should be screened regularly for the disease. Many doctors don’t do this, so it’s up to you to ask.
©Janet Farrar Worthington
