Patients and clinicians choosing among active surveillance, radical prostatectomy, and radiation therapy for low- to favorable intermediate-risk localized prostate cancer no longer need to worry that a treatment delay will lead to death. At the 38th Annual Congress of the European Association of Urology (EAU23) in Milan, Italy, investigators presented findings from the ProtecT trial demonstrating an approximately 97% prostate cancer-specific survival rate and a 78% overall survival rate at 15 years regardless of management choice.

“This is very good news,” according to lead investigator Freddie C. Hamdy, MBChB, FRCS, of the University of Oxford in England. “Most men with localised prostate cancer are likely to live for a long time, whether or not they receive invasive treatment and whether or not their disease has spread, so a quick decision for treatment is not necessary and could cause harm,” he stated in a news release from the University of Bristol.

The latest ProtecT findings were concurrently published in the New England Journal of Medicine (NEJM). In the original trial, investigators randomly assigned 1643 men (aged 50-69 years) diagnosed with localized prostate cancer from 1999 to 2009 to receive active monitoring, radical prostatectomy, or radiation therapy with neoadjuvant androgen deprivation therapy (ADT). Approximately 77.2% of the men had low-risk Gleason grade group 1 disease. At a median 15 years of follow-up, 45 men (2.7%) died from prostate cancer, including 17 (3.1%) in the active monitoring group, 12 (2.2%) in the prostatectomy group, and 16 (2.9%) in the radiation therapy group – differences that were not significant. A total of 356 men (21.7%) died from any cause at a comparable rate across groups.

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Rates of metastasis, local progression, and long-term ADT use were higher in the active monitoring than treatment groups, the investigators reported. Metastases developed in 9.4% of the active monitoring group, compared with 4.7% and 5.0% of the prostatectomy and radiation therapy groups. Clinical progression occurred in 25.9% vs 10.5% and 11.0%, respectively. Long-term ADT was received by 12.7% vs 7.2% and 7.7%, respectively. A quarter of the active monitoring group (24.4%) remained free of radical treatment and ADT at 15 years, the investigators reported. Dr Hamdy noted that active surveillance protocols have changed markedly since the start of the ProtecT trial and may change further. Panelists at the EAU session discussed whether MRI is enough for active surveillance for Grade Group 2 cancers or whether prostate biopsy is still needed. They also discussed the suitability of PSMA-PET in local evaluation of the prostate.

“Our findings provide evidence that greater awareness of the limitations of current risk-stratification methods and treatment recommendations in guidelines is needed,” Dr Hamdy’s team wrote in their paper. “Men with newly diagnosed, localized prostate cancer and their clinicians can take the time to carefully consider the trade-offs between harms and benefits of treatments when making management decisions.”

Some men with localized prostate cancer still die, the investigators highlighted. Contemporary risk stratification showed that up to 34% of the ProtecT cohort actually had intermediate- or high-risk prostate cancer at diagnosis. The trial was underpowered to discuss outcomes in these subgroups. According to the investigators, risk stratification needs to improve even further with better alignment of the tumor phenotype with its genotype.

“It’s also now clear that a small group of men with aggressive disease are unable to benefit from any of the current treatments, however early these are given,” Dr Hamdy stated in the news release. “We need to both improve our ability to identify these cases and our ability to treat them.”

“Taken together, the management of localized prostate cancer has undergone a wholesale change since 1999 when the ProtecT trial was started,” Oliver Sartor, MD, of Tulane School of Medicine in New Orleans, Louisiana, wrote in an NEJM editorial accompanying the article by Dr Hamdy and colleagues. “Even so, the results of this trial provide valuable data to inform decision making in the large group of men with low- or intermediate-risk prostate cancer.”

Also at EAU23, co-investigator Jenny L. Donovan, PhD, of the University of Bristol in the UK, revealed patient-reported outcomes from the ProtecT trial at 7-12 years. Urinary leakage requiring pads occurred in 18% to 24% of the prostatectomy group, compared with 9% to 11% of the active monitoring group and 3% to 8% of the radiation therapy group. Nocturia (voiding at least twice per night) occurred in 34% of the prostatectomy group, compared with 48% of the radiation therapy group and 47% of the active monitoring group at 12 years. Fecal leakage affected 12% of the radiation therapy group, compared with 6% of the other groups by year 12.

Erections sufficient for intercourse at 7 years were reported by 18% of the prostatectomy group, compared with 30% of the active monitoring and 27% of the radiation therapy groups. All men experienced low potency by year 12.

These findings were published concurrently in NEJM Evidence.


Plenary on prostate cancer: Screening and stratification. Presented at: EAU23 Congress, Milan, Italy, March 10-13.

Hamdy FC, Donovan JL, Lane JA, et al. Fifteen-year outcomes after monitoring, surgery, or radiotherapy for prostate cancer. New Eng J Med. Published online March 11, 2023. doi:10.1056/NEJMoa2214122

Sartor O. Localized prostate cancer — then and now. New Eng J Med. Published online March 11, 2023. doi:10.1056/NEJMe2300807

Donovan JL, Hamdy FC, Lane JA, et al. Patient-reported outcomes 12 years after localized prostate cancer treatment. NEJM Evidence. Published online March 11, 2023. doi:10.1056/EVIDoa2300018

Delaying treatment for localised prostate cancer does not increase mortality risk, trial shows. News release. University of Bristol; March 12, 2023.