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The optimal strategy for treating newly diagnosed high-risk prostate cancer remains unclear. More specifically, do these patients benefit more from radical prostatectomy or a radiotherapy-based approach?

A recent analysis aimed to help clarify the uncertainty.

The study, which evaluated individual patient data from two large contemporary randomized controlled trials, appeared to favor a radiotherapy-based treatment strategy over a surgery-based approach in this patient population. Compared with radical prostatectomy followed by personalized postoperative therapy, radiotherapy plus androgen deprivation therapy (ADT) was associated with a 32% relative reduction in distant metastases at 8 years.

However, the risk for death after distant spread was similar between the two strategies.

Overall, “we think this study moves the needle but does not end the debate,” corresponding author Daniel E. Spratt, MD, Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Cleveland, told Medscape Medical News.

“While it’s not a head-to-head randomized trial between surgery and radiation plus ADT, it provides compelling comparative data suggesting that radiotherapy plus ADT may not just be equivalent — it might be better when it comes to controlling disease and reducing treatment escalation,” Spratt explained.

William K. Kelly, DO, however, had a different take.

“The question still has not been answered,” given that there was no difference in overall cancer-specific survival, said Kelly, chair of medical oncology, Thomas Jefferson University Hospital, Philadelphia, who wasn’t involved in the analysis.

Currently, guidelines support the use of either radiotherapy with long-term ADT or radical prostatectomy with lymphadenectomy alongside selective postoperative care as options for men whose prostate tumors carry aggressive features. However, evidence from previous population studies has not revealed a clear preferred strategy, and head-to-head randomized data are lacking.

In an attempt to tease out a distinction in rates of distant disease recurrence between radiotherapy vs surgery, Spratt and colleagues pooled individual patient data from two contemporary phase 3 randomized controlled trials of men with newly diagnosed high-risk prostate cancer.

In one trial (NRG/RTOG 0521), patients received a radiotherapy-based treatment strategy, and in the other (CALGB 90203), patients received a radical prostatectomy-based approach. 

Together, the trials enrolled 1290 men — 557 in the radiotherapy trial and 733 in the surgery trial — followed for a similar length of time (median, 6.4 years). Treatments in the radiotherapy trial included pelvic irradiation (72-75.6 Gy) plus 24 months of ADT, with or without adjuvant docetaxel. The prostatectomy trial included personalized postoperative therapy with or without docetaxel and ADT.

In general, patients who underwent radical prostatectomy had more favorable prognostic features and were younger relative to those who had radiotherapy.

The cumulative incidence of distant metastasis at 8 years was significantly higher after surgery-based treatment than after radiation-based treatment (22% vs 15%; adjusted subdistribution hazard ratio [sHR], 0.58; P = .004). This finding was consistent across multiple subgroups and sensitivity analyses, as well as when restricting the analysis to patients eligible for both trials.

Overall, biochemical recurrence rates were also significantly lower at 8 years in the radiotherapy group (32% vs 68%; adjusted sHR, 0.24), as was the cumulative incidence of progression (35% vs 74%; adjusted sHR, 0.24), though the authors noted that definitions of biochemical recurrence were different in the two settings.

However, the researchers found no significant between-group differences in the incidence of deaths after distant metastasis (adjusted sHR, 0.98) or the incidence of deaths after progression (adjusted sHR, 0.85; 95% CI, 0.54-1.32).

What to Take Away

Overall, Spratt concluded that “this study gives clinicians a solid footing to explain why a radiation-first strategy may offer advantages” for disease control in men with high-risk prostate cancer.

“This comprehensive strategy seems to translate into fewer recurrences, fewer metastases, and less salvage of local or systemic therapies,” Spratt said.

For head-to-head findings, Spratt is looking ahead to the Swedish SPCG-15, an ongoing randomized controlled trial of radiotherapy vs radical prostatectomy, to provide more data on the risks and benefits of each approach.

Until then, Spratt’s strategy with patients is “honesty and clarity” about the similar survival outcomes, and believes the “real difference is in the treatment experience,” which favors radiation and ADT.

Mani Menon, MD, who was not involved in the research, called the study observations “intriguing” but did not think the findings warranted a shift in practice.

Declaring radiation superior would be “jumping the gun,” said Menon, with the Center of Excellence for Prostate Cancer at The Tisch Cancer Institute, Mount Sinai Health System, New York City.

All three experts agreed about the need to individualize care.

“We should always individualize recommendations,” Spratt said, adding that “all patients should be seen by both a urologic oncologist and a radiation oncologist to discuss treatment options for these patients.”

Looking at a specific scenario, Menon explained that if he were treating a 75-year-old person with very aggressive prostate cancer, “I would rethink surgery.” However, “for a 65-year-old with a similar disease, I don’t see much reason to change the way I’ve been treating them, and that would be with surgery,” he noted.

Individualized care is key, Kelly noted, because “patients with high-risk prostate cancer still represent a heterogeneous group of patients, and further work needs to occur to determine optimal local and systemic therapy for an individual patient.”

“As we counsel patients, we need to consider both their short- and long-term goals of care, as well as tumor characteristics and other comorbidities that may complicate any outcomes,” he said.

The study was supported by the Prostate Cancer Foundation. Spratt, Kelly, and Menon had no relevant disclosures.