Conducted on more than 2,100 patients in 18 countries, this phase 3 study shows that adding apalutamide to hormonal therapy around prostatectomy significantly reduces the risk of metastases or death. An advance that could reshape the management of high-risk localized prostate cancer.
When surgery is no longer enough: the challenge of high-risk prostate cancer
Every year, thousands of men are diagnosed with localized prostate cancer. When the disease is detected before the appearance of metastases, surgery or radiotherapy often offers encouraging prospects. But not all localized cancers are the same.
In patients classified as “high risk”, the threat remains significant despite treatment considered curative. Current data shows that between 40 and 50% of them will experience a relapse in the years following radical prostatectomy or radiotherapy combined with hormonal therapy.
This reality has serious consequences. Once the disease becomes metastatic, treatment options become more complex and life expectancy decreases considerably. Oncologists have therefore been seeking for several decades to identify strategies capable of hitting harder from the early stages.
This is precisely the ambition of the PROTEUS trial, the results of which were presented at the ASCO 2026 international cancer congress, then published in the New England Journal of Medicine.
Hitting the tumor before and after the operation: results that challenge
The study included 2,109 men with high-risk localized prostate cancer from 18 countries. All participants received androgen deprivation therapy (ADT), designed to deprive cancer cells of the hormonal stimulation they need to grow. But half of the patients also received apalutamide, an androgen receptor inhibitor already used in certain advanced forms of the disease.
The treatment was administered for six months before surgery and then for six months after radical prostatectomy.
The results observed at the time of surgery surprised the researchers. In patients treated with the apalutamide-ADT combination, 8.9% had a major pathological response — that is, complete or near complete disappearance of detectable tumor — compared to only 1% in the group receiving ADT alone.
But it is especially in the long term that the benefits appear remarkable.
After a median follow-up of 61.7 months, the therapeutic combination reduced the risk of developing metastases or death by 20%. Five-year metastasis-free survival was 78.2%, compared to 73.5% with standard treatment.
Another particularly telling indicator for patients: the time elapsed before a new treatment is necessary. This increased from 41.5 months to 74.2 months thanks to the addition of apalutamide, or almost three additional years without recourse to a new major therapeutic line.
For Dr. Mary-Ellen Taplin, of the Dana-Farber Cancer Institute and principal investigator of the study, these results open a new therapeutic perspective.
“The PROTEUS trial demonstrates that adding preoperative apalutamide to hormone therapy and surgery reduces the risk of metastases or death by 20%. This result is particularly important because it could reduce the need for subsequent treatments and their side effects, while increasing the chances of recovery. This approach, which combines systemic treatment with surgery, is already common practice in other aggressive cancers and has now demonstrated its effectiveness in patients with this disease.“.
Beyond the figures, the issue is profoundly human: to postpone the moment when the disease resumes its progression, to extend the years lived without metastases and to preserve an acceptable quality of life for longer.
A promising step forward, but still questions to be resolved
The enthusiasm generated by PROTEUS is nevertheless accompanied by several points of vigilance.
Therapeutic intensification has a cost in terms of adverse effects. Serious grade 3 or 4 events affected 39.6% of patients receiving the apalutamide-ADT combination, compared to 31% in the control group.
The researchers notably observed more skin rashes, but also hot flashes, urinary problems and erectile difficulties, effects already known from this type of hormonal treatments.
The trial also led investigators to strengthen preoperative cardiovascular assessment after several deaths occurred around the surgical period at the start of the study.
Despite these reservations, specialists believe that the results obtained could lastingly change practices.
“The results of this trial have the potential to reshape the standard of care for our high-risk prostate cancer patients.”said Professor Adam Kibel, urological surgeon at Mass General Brigham.
Apalutamide, marketed under the name ERLEADA by Johnson & Johnson, is already authorized in certain metastatic or castration-resistant forms. On the other hand, its use around surgery in high-risk localized cancers is not yet approved.
The PROTEUS data will now be examined by health authorities and learned societies. Their decision could determine whether this strategy becomes, tomorrow, a new therapeutic standard.
For the patients concerned, the hope is not that of a miracle treatment. It is perhaps even more valuable: to gain time on the disease, to delay its return and to extend years of life without metastases. In high-risk prostate cancer, this perspective already represents considerable progress.