Are men picking their best prostate options?

Clinical outcomes for low-risk disease are the same for surgical, radiation and surveillance options, but very different for quality of life.

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Active surveillance is the best option for many men with low-risk prostate cancer, according to a long-running UK study.

The findings support the approach given to around 80% of Australian men who fall into this category, said Professor Jeff Dunn AO, from the Prostate Cancer Foundation of Australia.  

“This trend largely reflects recent advances in diagnostic approaches which have strengthened our ability to determine the aggression of different prostate cancers and weigh this against the likelihood they will cause harm in the short and long term,” said the Foundation’s chief of mission and head of research. 

The study of 80,000 middle-aged UK men who took a PSA test found that those undergoing active surveillance had the same rates of death from prostate cancer as those who underwent prostatectomy or radiology treatment.

Around 3% of the study participants were diagnosed with localised prostate cancer with a life expectancy of at least 10 years, with a median PSA level of 4.6ng per millilitre (range, 3.0 to 18.9).

The men deemed to be at low-risk were randomly assigned to receive either active monitoring, prostatectomy or radiotherapy, in addition to three to six months of androgen-deprivation therapy. Researchers found that the incidence of death was low over the 15-year follow up, at 3.1% in the active monitoring group, 2.2% in the prostatectomy group and 2.9% in the radiotherapy group.

One surprising finding was that while 9.4% of the active monitoring group eventually metastasised, which was almost double the other groups, this had little effect on mortality.

“The higher incidence of metastatic disease in the active-monitoring group at 10 years was anticipated to have an effect on prostate cancer-specific mortality at 15 years, but this was not the case,” the authors said.

“Among the 40 men in whom metastatic disease had been diagnosed at 10 years, the risk of death from prostate cancer was lower among those in the active monitoring group (3 of 22 [13.6%]) than in either the prostatectomy group (2 of 8 [25.0%]) or the radiotherapy group (7 of 10 [70.0%]).”

“Our findings indicate that depending on the extent of side effects associated with early radical treatments, more aggressive therapy can result in more harm than good. Clinicians may avoid overtreatment by ensuring that men with newly diagnosed, localized prostate cancer consider critical trade-offs between short-term and long-term effects of treatments on urinary, bowel, and sexual function, as well as the risks of progression,” the authors wrote.

Men may not realise they have choices

Associate Professor Weranja Ranasinghe, spokesperson for the Urological Society of Australia and New Zealand, said that doctors were now better able to identify the patient’s risk profile accurately, thanks to both technology such as MRI and PSMA scans, as well as many risk stratification tools that take into account factors like age, family history, biopsy results, digital rectal examination and PSA density.

“The key message now is to identify prostate cancer early in order to utilise these new tools and help patients make the right decisions about whether to undergo active surveillance or pursue active treatment,” said Professor Ranasinghe.

It also helped to remind patients that active surveillance was not a hands-off approach. “The fact that you’re regularly monitoring them with PSA tests, clinical examinations, MRI, and plus or minus biopsies is quite reassuring to a lot of patients,” he said.

Some patients who needed treatment were very focussed on the surgical option, and could be resistant to considering other options, Professor Ranasinghe said. Urologists discuss all options with their patients and most of them would be offered a radiation oncology appointment, he said, though some refused.

“Surgery and radiation have similar cancer outcomes, so treatment depends on what’s important to the patient. The side effect profile of the treatment plays a huge role in determining which treatment you choose, and in appropriate patients, surveillance offers a great option to reduce or avoid the side effects associated with treatment,” said Professor Ranasinghe.

Radiation oncologist Professor Jeremy Millar, clinical lead at the Prostate Cancer Outcomes Registry Australia and New Zealand, said that evidence on side-effects and outcomes, and patient anxiety weren’t the only things driving patient choices. 

“Even important high-quality long-term work like this does not change practice quickly – patterns of practice have a momentum of their own, determined by fashion, tradition, surgical or radiation dogma and conservatism, training and availability, public perceptions and marketing, policy and financial frameworks, constraints and incentives, and availability of treatments and expertise,” he told The Medical Republic.

“In practically any dimension of adverse outcome in which there is a discernible gap between RT [radiotherapy] and RP [radical prostatectomy], RP is worse at practically every time point than radiation,” said Professor Millar.

“This is particularly true in the dimensions where there are larger problems (GU and sexual) and [side effects] men really care about: sexual function and incontinence.

“If you have your prostate removed then this does marginally improve the amount of nocturia and the frequency compared with no treatment or RT. In bowel function, the scores are reasonably good for all treatments (including observation) apart from an increasing bowel leakage. Here, about 12% reported once or more a week, compared with 6% with RP.”

Research published last year from the same trial suggested seed brachytherapy has a more favourable side-effect profile than radiation therapy – fewer sexual side-effects, less faecal incontinence, fewer loose stools and fewer bloody stools. But its use had declined by about two-thirds in the last decade, despite increasing prostate cancer cases, “almost entirely for the other factors I mentioned above”, Professor Millar said.

“This sort of work might be a stimulus to turn this around, but the decline has a momentum that won’t change too quickly.”

According to the PCFA, newly diagnosed Australian men don’t tend to be aware of their treatment options. The organisation provides specialised support through Prostate Cancer Specialist nurses.

“[Their role] is to help raise understanding and inform treatment decisions, minimising all risks of harm and ensuring that the man’s clinical and psychological needs are immediately addressed and supported over the long-term,” Professor Dunn said.

“Health professionals and researchers who have questions about the treatment of prostate cancer are welcome to contact PCFA via 1800 22 00 99 or email Telenurse@pcfa.org.au.”

NEJM 2023, online 11 March