Patients with newly diagnosed low-risk or intermediate-risk prostate cancer could safely be monitored for disease activity without early treatment being needed according to conclusions from the Prostate Testing for Cancer and Treatment (ProtecT) trial that tested 82,429 British men for PSA between 1999 and 2009, among whom 2,664 were diagnosed with prostate cancer, published in the New England Journal of Medicine (DOI: 10.1056/NEJMoa1606221).
“Men could take their time to make the decision and they could consider active monitoring if they want to avoid side effects,” said first author Jenny Donovan OBE, FMedSci, PhD, Professor of Social Medicine at the University of Bristol, U.K.
She told Oncology Times that in their 6-year follow-up analysis of patient-reported outcomes quality-of-life issues emerged as important factors to be balanced against the potential benefits of reducing disease spread by active treatment with surgery or radiotherapy.
ProtecT included patients with intermediate-risk prostate cancer, unlike most other studies looking at surveillance, Donovan said. “Other studies tend to select very low-risk men only for active surveillance. We included low-risk men and some intermediate-risk men and these results suggest that some of these men could also be actively monitored,” she said, although she acknowledged progression was missed in some patients.
Outcome findings for localized prostate cancer 10 years after diagnosis in a cohort of 1,643 men randomized to three treatment approaches—active monitoring, surgery, or radiotherapy—showed no differences in disease specific or overall mortality between the groups. Surgery and radiotherapy reduced the spread of early prostate cancer but any mortality benefit of this beyond 10 years remained hypothesis, explained Donovan's co-author, Freddie C. Hamdy, MBChB, MD, FRCS, Professor of Surgery and Urology at the University of Oxford, U.K.
Patients in the surveillance arm agreed to a clinical approach that included crossover to active treatment with radiotherapy or surgery if needed at any time—which is why this approach was called “active monitoring” rather than “watchful waiting,” Donovan explained. “Watchful waiting doesn't have a policy of curative intent,” she noted, which contrasted to the policy followed in ProtecT. With active monitoring the intention had been to help men avoid active treatment until it was needed. “But if their disease progressed—or showed signs of progression—we wanted to enable them to have the radical treatment,” she said.
Around half of all patients in the monitoring arm eventually received active treatment, but delay in starting gave them a period free from side-effects, which had no impact on their risk of dying out to 10 years after diagnosis.
The study was able to gather hard data on outcomes thanks to the “amazing” response from patients—around 85 percent of them completing long questionnaires about the effects treatments had on urinary, sexual, and bowel function, said Donovan.
The majority of patients treated with radiotherapy or surgery had sexual dysfunction. “This was a very strong effect. [Only] about 10 percent were able to have erections firm enough to have intercourse at 6 months,” Donovan said, adding there had been some recovery from surgery—“but not a huge amount.”
While the initial impact of radiotherapy on sexual function was similar to that of surgery, there also had been a loss of sexual potency in the active monitoring cohort, reflecting the natural decline in sexual function as men age.
“At 6 months in the surgery group, 50 percent of the men needed to wear pads for urinary incontinence whereas none of them did at the beginning of the study. And by 6 years, one in five still needed to wear pads,” Donovan explained.
Irrespective of treatment only one percent of men had died from their prostate cancer after 10 years and the overall mortality was also unexpectedly low—10 percent. Donovan said they were pleasantly surprised and that there were factors that may have contributed to the low mortality rates. “When we set up the study we anticipated that mortality from prostate cancer would be around 10 percent. It's much lower than that in part because treatments for later disease have improved. Also, these men were fit and healthy enough to have the radical treatment. And that's the first time fit healthy men have been compared for all these treatments.”
In addition, patients who had active treatment were also free of serious psychological problems. “While there was some anxiety around [the time of] biopsy, once they were in the trial there was no increase in anxiety or depression at any point during the studies,” she said.
When asked what impact the new data should have on practice, Donovan said patients needed to weigh the side effects from available therapies against the potential long-term benefit radical treatments may bring by preventing progressive and metastatic disease in some men.
“There's a balance between these two things, so our main message is that men need to take into account all of these findings. They need to take their time over a decision. They don't need to rush because the survival rate is so high and men and their clinicians need to consider all these different issues of sexual dysfunction, incontinence, and bowel problems [and] then make informed decision[s] about what treatment they want.”
She said management of prostate cancer needed to take account of the ProtecT findings. “Based on these data, we now need to revise our active monitoring strategies. There's been no consensus over those and we'll need to think carefully about what active monitoring should be like in the future.”
In the accompanying comment published in the New England Journal of Medicine (DOI: 10.1056/NEJMoa1606220), Anthony V. D'Amico, MD, PhD, Chief of Genitourinary Radiation Oncology at Brigham and Women's Hospital and the Dana-Farber Cancer Institute in Boston and Professor of Radiation Oncology, Harvard Medical School, wrote that a median follow-up of 10 years was too short to evaluate any ultimate survival benefit in such a cohort, the finding of greater disease spread among men assigned to active monitoring was significant, and the health-related quality of life data from ProtecT could be used to help men select treatment.
Peter M. Goodwin is a contributing writer.