Deferred treatment, patient selection and the comparative benefits of surgical and medical options continue to present dilemmas in the everyday clinical decision-making of doctors, issues that were taken up in the second plenary session at EMUC17 which opened today in Barcelona.
The optimal primary treatment of prostate cancer (PCa) was up in the morning agenda with the ProtecT study results presented by Malcolm Mason (GB). Two other lectures in the same session by urologist Silvan Boxler (CH) and biostatistician Mahesh Parmar (GB) also examined the issues of carefully weighing which therapeutic options can deliver optimal care in primary, localised prostate cancer.
“What have we learned from ProtecT? And what was the situation before ProtecT?” asked Mason. Prior to the ProtecT study, Mason noted there were no reliable randomized clinical trials (RCTs) regarding comparison of surgery, radiotherapy or deferred treatments.
“We did have two RCTs comparing surgery with watchful waiting,” said Mason. “But then evidence is lacking and opinion abounds,” he said, whilst adding there was also bias that suggested surgery was better than radiotherapy.
He described the ProtecT trial (which PSA-tested around 82,429 men out of which 2,965 were found to have PCa) as the largest RCT to date that compared active monitoring, surgery and radiotherapy for PSA-detected localized prostate cancer.
In the ProtecT study, more than half had received treatment by 10 years, and approximately 80% of men on active monitoring had no sign of progression. Moreover, 44% of men on active monitoring avoided treatment.
According to Mason, the study showed that numbers needed to treat to prevent one man from developing metastases include 27 radical prostatectomies (RPs) and 33 radiation treatments. “To prevent one man from developing clinical progression, nine RPs or radiation have to be done,” he said. “These conclusions are based on 10-year data and we need to see what will happen at 15 and 20 years.”
Mason also said that in the context of localized disease in asymptomatic men detected by PSA, the following were observed:
- Very few men die of prostate cancer (1% at 10 years);
- Surgery and radiotherapy reduce risk of clinical disease production by half (preventing it in roughly 11% of men);
- The excess rate of metastases with active monitoring is very small (20 extra men out of 545, or 3.7%) so far;
- Surgery and radiotherapy are of equal efficacy, neither impacts (yet) on mortality; and
- Side effects from both surgery and radiotherapy have impact, though they are different in nature.
In his concluding remarks, Mason said it is not wrong to offer deferred treatment, but pointed out: “But it would be wrong to offer it without discussing the trade-off between avoiding treatment and a higher risk of disease progression. He said that in terms of efficacy, both surgery and radiotherapy can be offered to men with localized disease.
Meanwhile, Boxler said with modern staging and follow-up, patient selection remains crucial. “We can counsel our patients with more confidence. And we can make active monitoring/active surveillance an even safer option,” he said. “Treatment options are equal- but they might be even more equal in the future.”
Statistician Mahesh Parmar (GB) examined the ProtecT 10-year outcomes from a statistician’s perspective in combination with the PIVOT study, noting that conclusions from both studies showed there is no evidence that surgery or radiotherapy improve prostate-cancer specific survival in men whose disease is detected by a PSA test.
“Absolute risk of dying from prostate cancer is small, around 4% and the relative risk of dying from prostate cancer is small, 10 to 15% of all deaths are from prostate cancer,” Parmar said. Personally, he said he would not choose to get his PSA tested.
“I should not spend my time trying to show a new treatment improves long-term outcomes in M0 (non-metastatic) disease,” he said, a statement which triggered further comments and questions from the audience during the Q&A segment.