Survival in Stage IV Gastric Cancer Better With Surgery and Radiation

February 08, 2013

By James E. Barone MD

NEW YORK (Reuters Health) Feb 08 - Patients who present with metastatic gastric cancer survive longer if they receive surgery, radiation or both, according to a review of the Surveillance, Epidemiology, and End Results (SEER) database.

Researchers at the Moffitt Cancer center in Tampa found that both median survival in months and two-year survival rates were significantly improved.

Asked about the impact of these findings on patient care, Iead author Dr. Ravi Shridhar told Reuters Health via email, "Every patient is going to have to be evaluated individually. Results from SEER should never be used to formalize treatment recommendations."

Dr. Shridhar, a radiation oncologist, added that SEER data are hypothesis generating and can serve to justify clinical trials to address the role of locoregional therapy in metastatic gastric cancer.

Few papers have addressed the role of surgery and radiation for stage IV gastric cancer, and the impact of radiation on survival in these patients has not been previously reported.

For the new analysis, the authors studied data from 2004 to 2008 on 5,072 patients. The cohort did not include anyone who lived less than three months after diagnosis of stage IV gastric cancer, since surgery or radiation would likely not have affected their outcomes.

Median survival and two-year overall survival were seven months and 8.2% in the 3,069 patients who received neither radiation nor surgery, vs eight months and 8.9% in the 806 patients treated only with radiation; 10 months and 18.2% in the 957 patients treated with surgery only; and 16 months and 31.7% in the 240 patients who received both surgery and radiation. The difference was highly significant (p<0.00001).

On multivariate analysis, surgery alone and radiation with surgery were associated with better survival but radiation alone was not.

On the other hand, increased age, the presence of T4 tumors or N3 nodes, signet ring histology and peritoneal metastases were associated with higher mortality rates.

In the surgery patients, resection of fewer than 15 lymph nodes was associated with increased mortality. Other factors, including tumor and nodal stage, tumor location and histologic grade and sex did not significantly predict survival.

The authors acknowledged several important limitations of their work, which are common to all studies based on SEER data. Whether patients received chemotherapy and which regimens were given are not included. The margin status of surgical resection and extent of lymph node removal were unknown. Details of radiation techniques, fields and doses were lacking. The basis for the clinical decisions about whether to use surgery or radiation was also unknown.

Dr. Masahide Ikeguchi, a surgical oncologist at Tottori University in Yonago, Japan was not an author of the study. In an email to Reuters Health, he noted that the paper is well documented. But, he too noted some ambiguities, such as the lack of information on chemotherapy and the extent of the gastric surgery.

The problem, he said, is that "the prognosis of patients who underwent R0 or R1 gastrectomy should be better than that of patients who underwent R2 operation, meaning they had residual tumor."

There are two prospective trials of palliative surgery and chemotherapy ongoing in Japan and Korea.

But because of large geographic variability in treatment and survival in gastric cancer, Asian data usually can't be reproduced in the West. "The Asians and Europeans for the most part don't radiate gastric cancer either in the preoperative setting or the postoperative setting," Dr. Shridhar said, not because of poor trial design, but rather because of "significant pharmacogenomic differences between Asian and Western populations." He believes a similar trial should be initiated in the U.S.

"Many Japanese doctors believe that the radiosensitivity of gastric cancer cells is not high, so radiotherapy is not suitable for gastric cancer," Dr. Ikeguchi said. "But a U.S. randomized controlled trial showed that postoperative chemoradiation improves the probability of survival."

Dr. Ikeguchi noted that a few hospitals in Japan have recently used chemoradiation to control local progression in patients with unresectable gastric cancer. He expects clinical trials of chemoradiation for gastric cancer will be done in Japan.

Dr. Shridhar says that from a palliative standpoint, radiation is justified for pain, bleeding, or obstruction. "If a metastatic patient were to undergo surgery with negative lymph nodes and negative margins, I would not recommend radiation," he added. If there were positive nodes or positive margins, he would offer radiation, as long as other metastatic disease sites are not rapidly progressing.

For each patient, Dr. Shridhar says, the extent of metastatic disease, response to chemotherapy, and performance status will impact the decision to use locoregional therapy, "after a thorough discussion in a multidisciplinary clinic and tumor board."


Cancer 2013.