Gallbladder Cancer Outcomes May Improve With Radiation

August 08, 2013

By James E. Barone MD

NEW YORK (Reuters Health) Aug 08 - Compared with surgery alone for gallbladder cancer, surgery plus postoperative radiotherapy (RT) yields better short-term survival, says a team from Johns Hopkins.

Long-term survival wasn't improved, however, which ""intuitively may make sense as RT is a local therapy," lead author Dr. Timothy M. Pawlik told Reuters Health by email.

"Therefore," Dr. Pawlik added, "the administration of RT may consolidate local therapy following surgery and lead to better short term outcomes."

Ultimately, however, long-term survival is probably dictated by the overall biology of the disease and distant failure, which are less likely to be influenced by a local therapy such as RT, he noted.

As reported online July 22 in Surgery, his team used the Surveillance, Epidemiology, and End Results (SEER) database to study 5,011 patients treated from 1988 to 2009. The median age was 72. Almost 75% were women, and nearly 80% were white.

Two-thirds of the tumors (66.2%) were intermediate to poorly differentiated; 63.7% of patients were free of lymph node metastases on presentation.

The median survival was 17 months, with one- and five-year survival rates of 60% and 26.4%, respectively. Survival was significantly worse for men, older patients, and those with tumors of intermediate or poor histology, nodal metastases, or extension through the serosa.

Of the overall cohort, 899 (17.9%) received RT. Those who got radiation were significantly younger, more often had advanced tumors histologically, positive lymph nodes and extension of the tumor into adjacent organs.

Radiotherapy was linked with significantly better one-year survival (68.2% vs 58%), but at five years, only 20.2% of radiated patients were still alive, vs. 28% of those who had surgery only. This pattern persisted even after RT was analyzed as a time-varying covariate and other confounding variables were taken into account.

In a propensity-matched analysis of 1,788 patients, half of whom had surgery alone and half who had surgery plus radiation, the addition of radiation appeared to prolong survival to 18 months, from 11 months with surgery only (p<0.001).

After excluding those who died within 90 days of operation, patients who underwent radiation still had a short-term survival benefit, (HR 0.66; p<0.001).

But with or without the exclusion of those who died within 90 days, the five-year survival rate did not differ between the two propensity-matched groups.

Dr. Pawlik said, "Looking at our data and the collective data in the literature, patients with a positive surgical margin and those patients with lymph node metastasis should be strongly considered for RT as these patients are at the highest risk of both local and distant failure."

The shortcomings of the SEER database limit the impact of the study. Among the missing treatment details were the radiation fields and dosing, status of tumor margins, and types and doses of chemotherapy.

"At Johns Hopkins, we have already been generally offering patients with residual disease (i.e., positive surgical margins) and those patients with lymph node metastasis RT," said Dr. Pawlik.

He feels that general surgeons who see patients with gallbladder cancer should ensure that these patients are seen in a multi-disciplinary setting. Many patients will present with incidental disease discovered after a laparoscopic cholecystectomy. These patients should be referred for a more definitive oncological operation that includes a liver resection, lymphadenectomy, and possible resection of the common bile duct.

"Depending on the final pathology from this oncological operation, patients with microscopic or macroscopic disease at the surgical resection margin and those with lymph node metastasis should be referred for consideration of RT and chemotherapy," he said.

Data from the current study would suggest that RT provides patients with at least a short-term survival benefit, although the impact of RT on long-term survival does not seem to be as pronounced.


Surgery 2013.


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