RT FOR RETROPERITONEAL SARCOMAS

A new study further supports the use of radiotherapy in the treatment of retroperitoneal sarcoma.

The finding comes from two large case-control analyses of 9068 patients with localized primary retroperitoneal sarcoma found in the US National Cancer Data Base.

Compared with surgery alone, survival improved significantly after both preoperative radiotherapy (hazard ratio [HR], 0.70; P.0001) and postoperative radiotherapy (HR, 0.78; P < .0001).

"This benefit was reported whether radiotherapy was delivered in the preoperative or postoperative period," Daniel P. Nussbaum, MD, from Duke University Medical Center in Durham, North Carolina, and colleagues write in a report published online in the July issue of The Lancet Oncology.

"Notably, the effect of both preoperative radiotherapy and postoperative radiotherapy on overall survival was maintained for patients treated at academic and high-volume institutions," the researchers write.

"Taken together, these data counter consensus guidelines, and suggest that most patients with resectable retroperitoneal sarcoma should be assessed within a multidisciplinary sarcoma team to consider radiotherapy," they add. To date, there are no randomized data available on the use of radiotherapy in retroperitoneal sarcoma, the researchers point out, and retrospective data have produced conflicting results.

Some studies suggest that radiotherapy does not improve local recurrence-free survival or overall survival; other studies suggest that local control is improved with radiotherapy but overall survival is not. There are also four small studies showing that perioperative radiotherapy is associated with both improved local recurrence-free survival and overall survival, Dr Nussbaum and colleagues note.

Waiting for Results From Randomized Trial 

The ongoing randomized European Organisation for Research and Treatment of Cancer (EORTC) trial (62092-22092; NCT01344018) may shed new light on a situation that has surgical and radiation oncology experts stymied. It is predicted that this international phase 3 randomized controlled trial comparing preoperative radiotherapy followed by en bloc resection to surgery alone will be completed in 2020. A total of 256 participants will be enrolled to detect a 20% improvement in 5-year abdominal recurrence-free survival.

The researchers warn, however, that the EORTC trial could be underpowered to identify a difference in overall survival.

"Thus, our results might provide additional evidence that radiotherapy is associated with improved overall survival," they suggest. "If the EORTC study shows an improvement in local recurrence-free survival with the use of preoperative radiotherapy, this would further support the increasing use of radiotherapy for patients with retroperitoneal sarcoma."

In an accompanying editorial, Elizabeth H. Baldini, MD, MPH, from the Department of Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts, suggests that until results from the EORTC trial become available, clinicians should "continue to study retroperitoneal sarcoma cases carefully

This includes stratifying treatment strategy by histologic subtype and collecting quality-of-life data, she adds.

"Given that retroperitoneal sarcoma is rare and, in fact, is a group of diseases with different biologies, best practice is to refer such patients to sarcoma centers for management," Dr Baldini told Medscape Medical News.

Retroperitoneal sarcoma should be diagnosed by core biopsy rather than marginal excision, she emphasized. "Unfortunately, many patients with retroperitoneal sarcoma undergo initial suboptimal excision, which can compromise subsequent treatment options."

In her editorial, Dr Baldini cites several other studies, including that by the Retroperitoneal Sarcoma Working Group, which examined outcomes stratified by histologic subtypes. It found that patients with well-differentiated liposarcoma had an excellent 8-year overall survival of more than 80%.

While evidence suggests that aggressive surgery and radiotherapy may be effective for well-differentiated liposarcoma, there are quality-of-life trade-offs, Dr Baldini says. More study is needed to determine which approach is better: more aggressive initial treatment or less aggressive upfront treatment with more frequent interventions for local recurrence.

"Probably, the optimum approach for well differentiated liposarcoma will be personalized and established in association with an individual's competing risks," Dr Baldini concludes.

Study Details

For the study, Dr Nussbaum and colleagues conducted two propensity-matched analyses. Using the nationwide clinical oncology database, they were able to focus exclusively on adult patients with localized, primary retroperitoneal sarcoma who were diagnosed from 2003 to 2011.

Patients were sorted into three groups: 563 who received preoperative radiotherapy, 2215 who were given postoperative radiotherapy, and 6290 who underwent surgery but not radiotherapy. Patients who received both preoperative and postoperative radiotherapy were excluded, as were those who received intraoperative radiotherapy.

Parallel propensity score-matched datasets were created for patients who received preoperative radiotherapy or postoperative radiotherapy versus those who received no radiotherapy.

Matching was done at a ratio of 1:2 for the preoperative radiotherapy dataset and 1:1 for the postoperative radiotherapy dataset and resulted in two comparison groups. There were negligible differences in all demographic, clinicopathologic, and treatment-level variables, the researchers said.

Median follow-up was 42 months for the preoperative radiotherapy group vs 43 months for the no radiotherapy group. Median overall survival was 110 months versus 66 months, respectively.

In the matched case-control analysis for postoperative radiotherapy, median follow-up time was 54 months for patients who received postoperative radiotherapy and 47 months for patients who had no radiotherapy. In these two groups, median overall survival was 89 months vs 64 months, respectively.

Although the authors acknowledge that their results are not definitive, the current study does many strengths, Dr. Baldini writes in her editorial. These include its large sample size, comprehensive analysis, and the fact that it was carried out at a time of important treatment advances.