Positive surgical margins do not independently predict prostate cancer mortality

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Inclusion of postoperative radiotherapy adds to previous studies

The "important and new aspect of this study," said Dr. Markus Graefen and Dr. Hartwig Huland, is that it accounted for postoperative radiotherapy. Previous studies modeled only fixed pathologic variables.

The data show that a positive surgical margin "is the product of a large cancer with a bad prognosis rather than an independent risk factor" for cancer-specific mortality, they said.

However, the study could not address whether or not to withhold early radiotherapy and wait for a PSA relapse to deliver early salvage radiotherapy. That answer requires results from the RADICALS (Radiotherapy and Androgen Deprivation in Combination after Local Surgery) study, which randomized patients to adjuvant radiotherapy or early salvage radiotherapy with and without additional hormonal therapy.

In the meantime, clinicians can help ease patients’ fears by explaining that positive surgical margins indicate the need for further treatment, but do not independently increase their risk of dying from prostate cancer.

Dr. Markus Graefen and Dr. Hartwig Huland are with the Martini-Klinik Prostate Cancer Center, University-Hospital Hamburg-Eppendorf, Germany. These remarks were taken from their editorial accompanying Dr. Stephenson’s report (Eur. Urol. 2014;65:681-2).



Positive surgical margins alone do not predict death from prostate cancer in men who undergo radical prostatectomy, investigators reported in the April issue of European Urology.

Positive surgical margins (PSMs) were not significantly associated with prostate cancer–specific mortality after adjustment for fixed covariates and postoperative radiotherapy, reported Dr. Andrew J. Stephenson, of the Cleveland Clinic’s Glickman Urological & Kidney Institute, and his associates.

Investigators analyzed data from 11,521 men with localized prostate cancer. Patients had undergone radical prostatectomy at four universities and cancer centers between 1987 and 2005.

At 15 years of follow-up, the prostate cancer–specific mortality for men with negative surgical margins was 6%, compared with 10% for men with PSMs (P less than .001).

But PSMs did not independently predict prostate cancer–specific mortality in regression models, the investigators reported (Eur. Urol. 2004;65:675-80).

That finding was true when researchers modeled only fixed covariates, such as age, Gleason score, seminal vesicle invasion, lymph node involvement, prostate-specific antigen (PSA), and extraprostatic extension (hazard ratio, 1.04; 95% confidence interval, 0.7-1.5), and also when they adjusted for postoperative radiotherapy, either as a single parameter (HR, 0.96; 95% CI, 0.7-1.4) or as early versus late treatment (HR, 1.01; 95% CI, 0.7-1.4).

The lack of an association called into question "the rationale for postoperative radiotherapy for PSMs in the absence of other adverse features," as well as "the relevance of PSM rates as a measure of surgical proficiency," the investigators said.

Even expert pathologists may not agree on PSMs and whether PSMs could be artifacts from surgery or pathologic processing, they noted. In addition, residual cancer from PSMs could lack biological characteristics needed for progression.

However, PSMs "should be avoided" because they worry patients and significantly increase the risks of biochemical recurrence and need for secondary treatment, Dr. Stephenson and associates said.

All patients in the study were treated at high-volume hospitals, and PSMs at low-volume hospitals could have a different prognosis. The study also lacked data on length and number of PSMs, the investigators noted.

Dr. Stephenson was partially supported by the Robert Wood Johnson Foundation Physician Faculty Scholars Program and the Astellas/American Urological Association Rising Stars in Urology Program. He reported no relevant financial conflicts of interest.

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