For men with a localized recurrence following prostate cancer radiotherapy, salvage treatment with either focal therapy or surgery may offer comparable long-term cancer control, but focal therapy comes with far fewer complications, an international cohort study shows.

Researchers found that 10-year cancer-specific survival was similarly high regardless of which salvage therapy approach patients received — at 92% with focal therapy (high-intensity focused ultrasound or cryotherapy) and 99% with radical prostatectomy.

The groups did diverge, however, when it came to treatment complications. Men who underwent surgery had a ninefold higher risk for major perioperative complications than those who received ablative therapies.

The study, published in JAMA Oncology, is the first to report survival data beyond 5 years with salvage focal therapy for radiorecurrent prostate cancer, according to lead author Alexander Light, MBBS, of Imperial College London in London, England.

Salvage radical prostatectomy is effective, he said, but also “very morbid.”

“We show that salvage focal therapy is a newer alternative that is less morbid [and] potentially just as effective for treating these recurrences,” Light said.

Amar U. Kishan, MD, chief of the genitourinary oncology service at the University of California, Los Angeles, agreed.

He noted that there is a long-standing concern about the morbidity of salvage prostatectomy, leading to an “oversimplified” belief that patients cannot have surgery after radiotherapy.

This study shows that’s not true, Kishan said. However, he added, it also suggests that “surgery may not be necessary, as other effective and well-tolerated options exist.”

Currently, most men with radiorecurrent prostate cancer receive androgen-deprivation therapy, but the treatment has bothersome side effects and is not curative. Studies suggest that salvage radical prostatectomy can offer durable cancer control, but substantial side effects are common — including erectile dysfunction in up to 85% of patients and urinary incontinence requiring daily pad use in roughly 60%.

Salvage focal therapy has emerged as an alternative, but studies comparing it to prostatectomy have been lacking.

To investigate, Light’s team analyzed data from various centers in the UK and other countries, spanning the years 2000 to 2024. They included 923 patients with biopsy-confirmed, localized recurrent prostate cancer following radiotherapy with either external beam radiotherapy, brachytherapy, or both.

Of the 419 patients undergoing salvage focal therapy, 78% received high-intensity focused ultrasound, and the rest got cryotherapy. Among 504 surgery patients, three quarters underwent open surgery, while the remainder had robot-assisted surgery.

The researchers created a matched cohort using variables such as tumor stage, grade group, prostate volume, and number of years between primary and salvage treatments. After matching, there were 277 patients in each treatment group.

In terms of survival outcomes, 5-year cancer-specific survival was 99% in both groups, while 10-year cancer-specific survival was 92% (95% CI, 86%-98%) for patients receiving focal therapy and 99% (95% CI, 97%-100%) for those undergoing radical prostatectomy. The restricted mean time lost was -0.09 years (95% CI, -0.22 to 0.03; P = 0.15).

In the unmatched cohort, 69 patients died following focal therapy and 67 died following surgery. Ten-year overall survival was 57% (95% CI, 44%-70%) in the focal therapy group and 72% (95% CI, 61%-83%) in the surgery group, with no significant difference in restricted mean survival time (-0.13 years; 95% CI, -0.86 to 0.60; P = 0.72). 

In the matched cohort, the Kaplan-Meier curves for overall survival crossed at around 7 years after salvage treatment, with surgery associated with significantly worse survival up to 5 years but significantly better survival beyond 5 years.

As for perioperative complications, 24 patients (5.7%) experienced complications with focal therapy in the unmatched cohort, compared with 302 (59.9%) undergoing surgery. For major complications, the percentages were 1.4% for focal therapy and 12.5% for surgery.

In the matched cohort, patients who underwent salvage prostatectomy had greater odds of experiencing any complication (odds ratio [OR], 24.20; P < 0.001) or major complications (OR, 9.31; P < 0.001). The most common complications included vesicourethral anastomotic leak or stricture, rectal injury or fistula, hemorrhage, and urinary infection.

According to Light, the durable effectiveness and relatively low morbidity with focal therapies may allow more men to be deemed eligible for salvage treatment.

However, an accompanying editorial noted that the study had many limitations, including unmeasured residual confounders that may have affected patients’ outcomes, such as baseline urinary, bowel, or sexual function, performance status, and radiation dose from the initial radiotherapy.

The findings also raise important questions, wrote John Nikitas, MD, and Neha Vapiwala, MD, both from the University of Pennsylvania in Philadelphia. For one, it’s unclear how another salvage therapy option — reirradiation — could fit in, and future analyses that include that approach will be “invaluable,” they said.

Another open question is how pathologic findings from biopsy specimens at the time of recurrence should guide treatment. It remains to be seen, for example, whether higher-risk patients have better disease control with whole-gland therapies than with focal therapies, the editorialists pointed out.

Finally, they wrote, the extent to which perioperative complications from salvage prostatectomy translated into long-term problems with urinary and sexual function is unknown.

Data on patient-reported quality of life outcomes would be informative, they noted.

Light reported receiving research funding from the UK National Institute for Health and Care Research Doctoral Fellowship and The Urology Foundation. Kishan reported having been a consultant to Lantheus and Novartis and owning stock options in MiraDx and Alethian AI.