Confirming a Role for Adjuvant XRT in the Management of Pancreatic Cancer

Abstract & Commentary

By William B. Ershler, MD, Editor

Synopsis: Two recent reports examining NCI-SEER registry data demonstrate improved overall survival when external beam radiation therapy is applied in an adjuvant setting for those with pancreatic cancer.

Sources: Hazard L, et al. Radiation therapy is associated with improved survival in patients with pancreatic adenocarcinoma: results of a study from the Surveillance, Epidemiology, and End Results (SEER) registry data. Cancer. 2007;110:2191-2201.

Artinyan A, et al. Improved survival with adjuvant external beam radiation therapy in lymph node-negative pancreatic cancer. A United States Population-based assessment. Cancer. 2008;112:34-42.

The adjuvant use of external beam radiation for patients with pancreatic cancer has been controversial.1 However, two recent reports, both of which capitalized on the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results (SEER) registry have demonstrated added benefit in selected clinical settings. Hazard and colleagues from the University of Utah performed a retrospective analysis on 3008 patients reported to the registry from 1988 to 2002 who had adenocarcinoma of the pancreas and who underwent cancer-directed surgery. Overall and cancer-specific survival for these patients was performed using the Kaplan-Meier method. Comparative risks of mortality were evaluated by using multivariate adjusted Cox regression models.

Of 3008 patients, 1267 (42%) received radiation therapy. Overall survival improved significantly in patients who received radiation therapy, with a median survival of 17 months and a 5-year overall survival rate of 13% in patients who received radiation compared with 12 months and 9.7%, respectively, for patients who did not receive radiation therapy (P <.0001 on multivariate analysis radiation therapy was associated with improvement in overall survival patients who had direct extension beyond the pancreas and regional lymph node involvement>P < .01) but not in patients with T1-T2N0M0 disease (P > .05). Radiation therapy was associated with improvement in cause-specific survival in patients who had regional lymph node involvement (P <.02 but not in patients who had t1-2n0m0 disease or direct extension beyond the pancreas without lymph node involvement>P > .05). Differences in overall and cause-specific survival among patients who received preoperative vs postoperative radiation therapy did not reach statistical significance.

In a report published in the same journal just a few months later, Artinyan and co-workers from the City of Hope National Medical Center in Duarte, California (and also analyzing SEER registry data), undertook a more focused look at the success of adjuvant radiation therapy for patients over the same time period (1988-2003). Their focus was on localized, node negative pancreatic cancer and not on those with more advanced disease. Once again, Kaplan-Meier survival curves were constructed to compare overall survival between patients who did and did not receive adjuvant radiation therapy (RT). Multivariate Cox regression analysis was also used to determine the prognostic value of RT when additional clinicopathologic factors were assessed. In this analysis, particular attention was paid to the potential treatment selection bias of patients who had survival 3 months or less.

The analysis included data from 1930 surgical patients with N0 disease. For the overall group, the median survival was 17 months. Irradiated patients had significantly better survival compared with non-irradiated patients (20 months vs 15 months, respectively; P < .001). On multivariate analysis, having received adjuvant RT, age, grade, tumor classification, and tumor location remained independent predictors of survival. However, when patients with survival < 3 months were excluded from the analysis, the observed benefit of RT (in univariate comparison) was no longer apparent. However, on multivariate analysis, having received RT remained an independent predictor of improved overall survival (HR, 0.87; 95% CI, 0.75-1.00; P=5.044).

Commentary

These two reports, capitalizing on the rich SEER data base, support a role for adjuvant external beam radiation therapy in conjunction with surgery for patients with pancreatic cancer. Long-term survival remains poor, but median survival appears to be enhanced by 4 to 5 months in treated patients. Of course, retrospective analyses such as these run the risk of treatment bias, but both research teams controlled as best possible by rigorous multivariate analysis.

What seems somewhat surprising is that analysis of basically the same dataset led to two different conclusions regarding treatment of node negative, locally confined disease. The Utah report (Hazard, et al) was not able to demonstrate RT-enhanced survival for those with T1-T2N0M0 in contrast to the significant RT survival enhancement for those with locally more advanced disease and/or lymph node involvement. The City of Hope analysis (Artinyan et al), was confined to that group which had shown no RT benefit in the Utah study, ie, locally confined, node negative. In their analysis, however, there was a larger cohort (1930 subjects compared with approximately 400 with that stage in the Utah report). The larger sample size may alone explain the different finding, although perhaps it also relates to the elimination of early death bias in the City of Hope report, an approach not taken by the Utah group.

Despite the minor discrepancy, the data are for the most part consistent and demonstrate a modest improvement in survival in those who had received adjuvant RT in conjunction with surgery. Whether such will become the standard approach will depend on local patterns of care and the experience of radiation oncologists applying external beam therapy under oftentimes difficult circumstances. Furthermore, the survival advantage needs to be presented in the context of added morbidity, an aspect not thoroughly evaluated in these reports. It is clear that adjuvant RT is warranted under certain circumstances, and these circumstances include patient directives as well as the availability of talented radiation oncologists.

Reference

1. Bergenfeldt M, Albertsson M. Current state of adjuvant therapy in resected pancreatic adenocarcinoma. Acta Oncol. 2006;45(2):124-135.