‘More rigorous’ discussion needed about potential complications after prostate cancer therapy
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Key takeaways:
- Prostatectomy and radiotherapy significantly elevated risk for urinary incontinence, sexual dysfunction and bladder cancer.
- The effect of these complications can last more than a decade after treatment.
Men treated with radiotherapy and prostatectomy for prostate cancer exhibit significantly higher risk for numerous urinary and sexual complications compared with the general population, according to results of a cohort study.
Urinary incontinence, sexual dysfunction and secondary malignancies are among the known adverse events that can occur after prostate cancer treatment.
However, the magnitude of risk for these complications must be quantified for patients so they can make more informed decisions, according to Joseph M. Unger, PhD, MS, associate professor at Fred Hutch Cancer Center.
“It’s really important for men not just to understand how commonly these complications can occur, but how far out in time they are still meaningful,” Unger told Healio. “It’s not just the acute complications in the first 2 years, although that is important. These treatments have durable implications out to 12 years.”
Background
More than 50% of men aged at least 80 years have developed prostate cancer, and 12.5% of all men are diagnosed with it during their lifetime, according to study background.
However, only 2.5% of men diagnosed with the disease will die of it.
A previous U.S. trial showed PSA testing did not reduce risk for prostate cancer mortality; however, a trial conducted in Europe showed a 21% reduction after 11 years.
Active surveillance has become a “preferred choice” for many men diagnosed with prostate cancer — particularly those with early-stage disease, Unger said. However, at least 50% of patients eventually receive treatment.
“Major guidelines for early prostate cancer detection do not include any quantitative assessment of what the risks for complications are over the short or long term,” Unger said. “They’re predicated on the idea that getting treated for your prostate cancer is necessarily a good idea without any drawbacks. But not a lot of men die of prostate cancer, and many more men die with prostate cancer as opposed to of it. The benefit of treatment for early prostate cancer may be fairly limited, even as the complications of prostate cancer treatment are very common.”
A ‘real control population’
Several studies have evaluated adverse events from prostate cancer treatments. However, many of those investigations have had shortcomings, Unger said.
They often focused on either urinary or sexual function, frequently used retrospective data, compared treatment modalities against one another, or evaluated adverse events over a short follow-up period.
“Depending on the way the studies were designed, it can often be the case that the risks for complications are underestimated,” he said. “For instance, if you’re comparing complications between prostatectomy and radiation therapy for a given outcome and your comparison is the other modality, that difference — as a statistic — has very limited meaning. You’re just comparing to the other modality. Both modalities are going to cause that complication. The real control population should be a control group of healthy men.”
Unger and colleagues used data from the Prostate Cancer Prevention Trial and the Selenium and Vitamin E Cancer Prevention Trial to investigate 10 treatment-related complications.
The complications included urethral stricture, placement of artificial urinary sphincter, placement of penile prosthesis, urinary incontinence, erectile dysfunction, radiation cystitis, radiation proctitis, bladder cancer, bladder cancer followed by cystectomy, and rectal cancer.
All participants had normal PSA scores and no diagnosis of prostate cancer when they entered those trials.
Researchers linked data from both studies with Medicare records and identified patients who had prostate cancer who received either prostatectomy or radiotherapy.
Investigators compared complications among trial participants and members of a control group, which included men without prostate cancer, as well as men who had developed prostate cancer but had not yet been treated.
The total cohort included 29,196 men (median age, 65.8 years; range, 65.4-70.9; 8.4% Black).
“What’s fundamentally different between our study and every other study is that we were able to compare complication rates between treated and untreated men, where the untreated men reflected the population of healthy men,” Unger said. “These men will also accrue complications. Older men have erectile dysfunction. They have urinary issues. It’s necessary to compare what happens after a prostate cancer treatment to men who have not been treated in a normal population, because that’s the only way to get a reliable estimate of the additional impact a prostate cancer treatment has on these sequelae.”
Findings
Researchers determined 3,946 men had been diagnosed with prostate cancer — the majority having early-stage disease. Of those, 655 underwent prostatectomy and 1,056 underwent radiotherapy.
After median follow-up of 10.2 years, men who underwent prostatectomy had a significantly higher 12-year risk for any complication than healthy men (HR = 6.57; 95% CI, 5.39-8.01). Men who received radiotherapy also exhibited higher risk for any complication (HR = 3.04; 95% CI, 2.51-3.67).
Prostatectomy increased 12-year risk for several complications, including any urinary or sexual complication (HR = 7.23; 95% CI, 5.96-8.78), urethral stricture (HR = 5.59; 95% CI, 3.39-7.55), erectile dysfunction (HR = 6.38; 95% CI, 5.18-7.85) and urinary incontinence (HR = 7.99; 95% CI, 6.64-9.61).
Radiotherapy significantly increased 12-year risk for any urinary or sexual complication (HR = 2.76; 95% CI, 2.26-3.37), urethral stricture (HR = 6.49; 95% CI, 4.71-8.94), erectile dysfunction (HR = 2.58; 95% CI, 2.03-3.29) and bladder cancer (HR = 2.78; 95% CI, 1.92-4.02).
Researchers acknowledged study limitations, including possible misclassification of claims data and a study population enrolled in a randomized cancer prevention trial, which could limit generalizability of the findings.
Unger and colleagues are investigating the impact of androgen deprivation therapy, with the goal of sharing data in the next year.
‘Rebalance’ treatment
Unger emphasized these data should not be used to make the case that men with prostate cancer should not get treated.
“The decision about treatment is a very a personal and complicated one, and men should be fully informed of what the risks and potential benefits are,” he said. “Our aim is to inform that discussion in a much more rigorous way. Rather than have the discussion amount to, ‘You have prostate cancer and here are the treatments,’ it should be, ‘You have prostate cancer. Here are the treatments, but there are also these risks for sequelae and complications. Here are the numbers. Here’s the magnitude of these risks over time compared with what is the possibility that this treatment could save your life.’”
Despite the increasing uptake of active surveillance, overtreatment in prostate cancer continues and must be reduced, Unger said.
“We're trying to rebalance the amount of treatment that is done for early prostate cancer by putting into the conversation between a man and his physician what the risks and benefits are,” he added. “We’re not saying you shouldn't be treated. We're saying you should be fully informed when you make that decision about whether to be treated, and too often that's not the case.”
For more information:
Joseph M. Unger, PhD, MS, can be reached at junger@fredhutch.org.
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