Men with localized prostate cancer who were randomized to delay treatment while receiving regular monitoring had the same high survival rate as those who had prompt surgery or radiation therapy, according to study results published in The New England Journal of Medicine and presented at the European Association of Urology conference in Milan.
About 97% of the men in this long-running study survived 15 years after their prostate cancer diagnosis regardless of which treatment they received. But delaying treatment—or skipping it entirely if the cancer does not progress—can enable patients to avoid side effects such as urinary incontinence and sexual problems.
“It’s clear that, unlike many other cancers, a diagnosis of prostate cancer should not be a cause for panic or rushed decision making,” Freddie Hamdy, MD, of University of Oxford, said in a press release. “Patients and clinicians can and should take their time to weigh up the benefits and possible harms of different treatments in the knowledge that this will not adversely affect their survival.” However, he cautioned, men with high-risk cancer should still be treated promptly.
Prostate cancer is the most common cancer (after noninvasive skin cancer) and the second-leading cause of cancer death among men in the United States. This type of cancer typically grows slowly, and only a small proportion of men who develop the malignancy will die from it. Treatment may include surgery to remove the prostate gland (prostatectomy), radiation to shrink tumors and androgen-deprivation therapy (medications to block hormones that spur prostate cancer growth). But active surveillance, meaning delayed treatment while undergoing regular testing for cancer progression, is an increasingly popular option.
Prostate cancer can be detected by a blood test that measures prostate-specific antigen (PSA), a protein produced by the prostate gland. But this test does not show how advanced the cancer is or how fast it will progress. Routine PSA screening is controversial. An elevated PSA level could lead to unnecessary invasive testing and treatment for many men whose cancer will never progress. On the other hand, some studies have found that lower screening rates are linked to more advanced diagnoses and higher mortality. According to the U.S. Preventive Services Task Force, screening should be an individual decision based on risk factors and personal preference.
Hamdy and colleagues with the ProtecT Study Group analyzed data from 82,429 men ages 50 to 69 years in the United Kingdom who received a PSA test between 1999 and 2009. Of these, 2,664 were diagnosed with localized prostate cancer. More than one third were deemed to have an intermediate or high risk of progression using modern methods.
A total of 1,643 participants enrolled in a trial to evaluate the effectiveness of different treatment approaches. About one third were randomly assigned to undergo surgery, a third had radiation plus hormone therapy and a third received active monitoring. After a median 15 years of follow-up, the researchers compared how many in each group died from prostate cancer, died from any cause, experienced disease progression or cancer metastasis or started long-term androgen-deprivation therapy. This is the first study to fully evaluate long-term outcomes of the three major approaches.
Almost all participants (1,610 men) completed follow-up. Overall, 45 men (2.7%) died from prostate cancer. Mortality rates were low and statistically similar across the three groups: 3.1% in the active-monitoring group, 2.9% in the radiation group and 2.2% in the surgery group. The likelihood of death from any cause was also similar in all three groups.
Clinical disease progression occurred in 25.9% of the men in the active monitoring group, 11.0% in the radiation group and 10.5% in the surgery group. Metastasis rates were 9.4%, 5.0% and 4.7%, respectively. Finally, 12.7%, 7.7% and 7.2% started long-term androgen-deprivation therapy. In the active-monitoring group, 133 men (24.4%) were still alive without receiving any prostate cancer treatment at the end of follow-up.
“After 15 years of follow-up, prostate cancer-specific mortality was low regardless of the treatment assigned,” the study authors concluded. “Thus, the choice of therapy involves weighing trade-offs between benefits and harms associated with treatments for localized prostate cancer.”
While fewer men who underwent surgery or radiation experienced disease progression, there were also drawbacks. A related analysis, published in NEJM Evidence, looked at patient reported outcomes in the same trial, focusing on functional and quality-of-life impacts of the different treatment approaches.
Over seven to 12 years of follow-up, overall quality-of-life scores were similar in the three groups. But there were differences in specific side effects.
Up to 11% in the active monitoring group and up to 8% in the radiation group experienced enough urinary leakage to require pads, but this reached 24% in the surgery group. Nearly half of the men in the monitoring and radiation groups (47% and 48%, respectively) but 34% in the surgery group had to get up at least twice in the night to urinate (which can be a consequence of prostate enlargement). Twice as many men in the radiation group (12%) experienced fecal leakage compared with the monitoring and surgery groups (6% each). At seven years, 30% of men in the active monitoring group, 27% in the radiation group and 18% in the surgery group reported having erections adequate for sexual intercourse, but rates were similar by 12 years.
“The active monitoring group experienced gradual age-related declines in sexual and urinary function, avoiding radical treatment effects unless they changed management,” the researchers concluded.
“Patients and doctors now have the necessary information on the long-lasting side effects of treatments to better understand the trade-offs between their benefits and harms,” said lead study author Jenny Donovan, PhD, from the University of Bristol. “Survival no longer needs to be considered when deciding on treatment—as that’s the same for all three options. Now men diagnosed with localized prostate cancer can use their own values and priorities when making the difficult decisions about which treatment to choose.”
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