Radical Prostatectomy Shows Comparable Outcomes to Radiation+ADT in Node-Positive Prostate Cancer

For decades, urologists have debated whether cutting out the prostate makes sense when cancer has already spread to the lymph nodes. The conventional wisdom, enshrined in national treatment guidelines, says no—surgery is for early disease, radiation plus hormone therapy for advanced. But a team at Mayo Clinic decided to test that assumption against real-world data, and what they found complicates the old certainty.

Dr. Gillian Murray presented the results at the 2026 North Central Section of the American Urological Association meeting. Her team had reviewed 403 men with clinically node-positive prostate cancer treated between 2016 and 2022: 253 underwent radical prostatectomy, and 150 received radiation therapy combined with androgen deprivation therapy, or ADT. The median follow-up stretched to 30 months. The question was straightforward: which approach kept men alive longer, cancer-free longer, and free from the need for additional treatment?

At first glance, the numbers seemed to favor surgery. In the raw, unadjusted analysis, men who had their prostates removed showed better outcomes across multiple measures—lower rates of clinical progression, lower rates of biochemical recurrence, fewer metastases, and better overall survival. The difference was statistically significant. But then the researchers adjusted for the variables that actually matter: patient age, disease severity, risk factors, and the fact that the two groups were not comparable to begin with. When they did, the picture inverted. Radiation plus ADT now looked superior on several fronts, with hazard ratios suggesting substantially lower risk of biochemical recurrence and clinical progression.

This is where immortal time bias enters the story. Men who undergo surgery and then develop a rising PSA face a wait before salvage radiation can begin—months or years in which they appear, on paper, to be doing well simply because time has passed. To account for this distortion, the team performed a landmark analysis, freezing the clock at two years and comparing only the men who survived that long in both groups. The results shifted again. At two years and beyond, there were no statistically significant differences between prostatectomy and radiation-plus-ADT across the endpoints that matter most: metastasis-free survival, cancer-specific survival, and overall survival. The only meaningful difference that persisted was a higher rate of biochemical recurrence in the prostatectomy group—a finding that makes biological sense, since radiation therapy is more effective at sterilizing the prostate bed than surgery alone.

Murray's conclusions were measured. Radical prostatectomy for node-positive disease does not appear to compromise a man's chances of staying free from metastases or dying from cancer compared to radiation and hormones. But it does carry a higher risk of PSA recurrence and the need for salvage therapy down the road. Adding ADT to prostatectomy did not improve metastasis-free or cancer-specific survival in this cohort. The surgery may be worth considering for carefully selected patients—those who want to postpone hormone therapy, those bothered by local prostate symptoms, those willing to accept the likelihood of future radiation and ADT if their PSA rises. But it requires honest conversation. A man choosing prostatectomy for node-positive disease is not avoiding systemic therapy; he is likely deferring it, trading the certainty of immediate hormone treatment for the probability of radiation and hormones later.

The study does not settle the debate. It is a single institution's experience, and the men who chose surgery may have differed in unmeasured ways from those who chose radiation. But it does suggest that the NCCN's cautious stance—recommending prostatectomy only for select patients—may reflect genuine uncertainty rather than settled science. For some men with node-positive disease, surgery remains an option worth discussing, provided they understand what comes after.