A study published in the New England Journal of Medicine in January 2017 indicates that men whose prostates are removed to treat prostate cancer are likely to survive longer if they take drugs to block the male hormone testosterone in addition to undergoing radiation therapy.
About 200,000 men are diagnosed with prostate cancer in the U.S. every year. As many as 75,000 of them undergo prostatectomy – surgery to remove the prostate and the cancer within. But of these 75,000, as many as 30 percent experience increases in their prostate-specific antigen (PSA) levels after surgery. PSA is a protein produced by cells of the prostate, and increasing PSA levels after surgery indicate that the cancer has returned.
Usually these men have clues as to the higher risk of their cancer at surgery, such as higher Gleason grade, a score we use to rank the aggressiveness of a cancer, or cancer near the edge of the removed prostate gland or in the surrounding tissue. Radiation has long been used to eliminate such re-growing disease, and the reported study now shows that adding hormone therapy helps further.
Related reading: PSA tests: Can they save men from prostate cancer?
So, if testosterone-blocking drugs can help prevent cancer recurrence in this setting, why not give them to every man after prostate cancer surgery along with standard radiation? Unfortunately, it’s not that simple. As we’ve believed for years, and as the study proves, the benefits of hormone therapy can be enormous – but not all men will benefit from it, and blocking testosterone in a man’s body has its own set of side effects.
Significant results when using hormone therapy
Radiation therapy gives us a good chance to rid the body of any remaining cancer cells that may have lingered after the prostatectomy. But radiation treats only the cells in the pelvis, where the prostate was removed. Hormone therapy, on the other hand, can treat cancer cells anywhere in the body and helps radiation work better in more aggressive disease.
The researchers in the New England Journal of Medicine study found that pairing radiation therapy with anti-androgen therapy (one class of male hormone-blocking drugs) for 24 months resulted in significant decreases in death rates. After 12 years, fewer than 6 percent of participants who received hormone-blocking drugs had died from prostate cancer as compared to more than 13 percent of participants who did not receive hormone-blocking drugs. The group who received drugs also developed metastatic prostate cancer at a 9 percent lower rate than the non-drug group.
Put another way, one prostate-cancer-related death was prevented for every 13 patients treated, and one case of cancer spread or metastasis was prevented for every 11 patients treated – both laudable achievements.
But anti-androgen therapy is not without side effects. As we’ve mentioned, not all patients benefit from the therapy. We must continue to consider whether the risks (side effects) outweigh the benefits (reduction in cancer recurrence and extension of life) for our prostate cancer patients. Talk to your doctor to get a full understanding of the risks and benefits of anti-androgen therapy if it’s recommended for your condition.
The side effects of anti-androgen therapy
This study launched in the 1990s, and much has changed in how we administer hormone therapy over the years. Today’s drugs are easier to administer as a long-acting shot that decreases the male hormone testosterone, which drives prostate cancer.
Most men tolerate anti-androgen therapy well. Some of the more common side effects include:
- Decreased sex drive
- Erectile dysfunction
- Hot flashes
- Weight gain
Men who undergo long-term therapy or have difficulty tolerating the drug may experience more severe side effects, such as:
- Bone density loss
- Irritability or mood swings
- Enlargement of breasts (gynecomastia)
Rarely, men who have pre-existing, significant conditions such as heart problems or diabetes may experience more pronounced side effects or worsening of their pre-existing disease. There also have been conflicting studies noting possible depression and risk for worsening of cognitive function in patients at risk for these issues, including the elderly and those with prior depression.
We continue to work to alleviate and avoid these symptoms. At the start of hormone therapy, we work with our patients to make it as tolerable as we can, including:
- Starting patients on Vitamin D and calcium, providing consultation with our endocrinology team about preserving bone health, and getting baseline bone density scans when indicated
- Encouraging men to commit to active physical therapy and aerobic exercise to limit weight gain, preserve muscle composition, and even retain urinary function and control it better
- Recommending medications to help with hot flashes and mood changes that can arise during hormone therapy
Our team also works with volunteer participants in ongoing clinical trials to use shorter durations and other forms of hormone therapy.
Confirming what we’ve practiced for years
We treat hundreds of men with prostate cancer each year, and many benefit from anti-androgen therapy. When we have a patient with an elevated PSA level after prostatectomy, our urologists and radiation oncologists work together to find an effective treatment that will decrease the risk of his cancer returning.
We ask ourselves:
- What was the grade of the cancer?
- Was it at the edge (margin) of the removed prostate gland?
- Was it in the attached seminal vesicles or extending beyond the capsule?
- Was there cancer in any removed lymph nodes?
- What is the trend of serum PSA since surgery?
- How old is the patient, what are his other medical issues, and what are his goals?
Armed with that information, we decide together whether the patient needs further treatment, and if so, whether he should receive radiation only or radiation plus hormone therapy, and for how long.
We’ve been considering these factors for a number of years when making treatment recommendations with the goal of providing hormone treatment to those who will benefit and avoiding it in those who won’t. So how did we do in anticipating the results of the study and being early adopters of its lessons as our experience matured over the last two decades of this study? Three out of three looks good to us!
- We infrequently operate on men with a Gleason cancer aggressiveness score of 6 or lower given our robust surveillance program for such patients. Our focus has been on those with higher grade disease, where we have long added hormone therapy to radiation when disease recurs after surgery. The majority of patients on this study fit this profile, reassuring us we are concentrating on the right ‘biology’ of patient.
- When a man’s PSA level is low, less than 0.5, we are more confident that radiation alone will prevent recurrence. Using ‘early’ radiation and higher doses with modern techniques has improved outcomes, and thus the addition of hormones is more carefully measured in such patients. This study did not find survival benefit for patients with PSA levels of less than 0.7, supporting our emphasis on this strategy.
- The study also confirms another of our standard practices: If a man’s PSA is above 0.7, all patients do better with added hormone therapy.
In all, this study verifies that, even when faced with severe, unfortunate PSA elevation recurrence after surgery, we must continue to step back and consider all clinical information before recommending a treatment plan.
No doubt, additional ongoing, large-scale trials like this one allow us to further refine our treatment practices and come closer to our overarching goal of giving as much treatment as needed while protecting patients from the side effects of unnecessary treatments. This research provides hope into eradicating recurrent prostate cancer after prostatectomy in future patients.