Analyses of mortality after breast cancer radiotherapy using randomized clinical trial data versus observational data produced strikingly different results, according to researchers.
Analyses of randomized data indicated radiotherapy reduced mortality after breast-conserving surgery and mastectomy in node-positive disease; by contrast, SEER data analyses showed radiotherapy was associated with a significantly larger reduction in breast cancer mortality after breast-conserving surgery but higher mortality after mastectomy. Among patients with node-positive breast cancer who underwent mastectomy and axillary dissection, radiotherapy was associated with lower mortality by clinical trial data (rate ratio, 0.84; 95% CI, 0.76-0.94) but was associated with higher mortality by observational data (1.34; 1.31-1.37).
Furthermore, analyses of randomized trial data indicated increased mortality from heart disease (1.27; 1.12-1.44) and lung cancer (1.78; 1.30-2.46) following radiotherapy, but analyses of SEER data indicated reduced mortality from heart disease (0.56; 0.53-0.60) and lung cancer (0.86; 0.75-0.99) associated with radiotherapy.
“It is not plausible that these negative associations in the SEER data are causal and, clearly, they are strongly influenced by factors other than the effect or radiotherapy,” wrote Dr. Katherine Henson of the University of Oxford (England), and colleagues (J Clin Oncol. 2016 Jan 18. doi: 10.1200/JCO.2015.62.0294).
“Randomized trials are needed wherever possible to investigate the effect of treatment on mortality from the original cancer,” according to the investigators, and, “selection biases can be problematic even when analyzing treatment-related toxicities using observational data.”
Analyses of randomized data demonstrated reduced breast cancer mortality associated with radiotherapy after breast-conserving surgery (0.82; 95% CI, 0.75-0.90). Compared with randomized data, analyses of observational data showed a much greater reduction in mortality associated with radiotherapy after breast-conserving surgery (0.64; 95% CI, 0.62-0.66).
Randomized evidence came from the Early Breast Cancer Trialists’ Collaborative Group, meta analyses of 17 trials (n = 10,801) of radiotherapy after breast-conserving surgery, 14 trials (n = 3,131) of radiotherapy after mastectomy, and 78 trials (n = 42,080) of mortality from causes other than breast cancer. Observational evidence came from the SEER data base (n = 393,840).
The researchers offered plausible explanations for selection bias that may have resulted in the divergent results calculated using observational data. Because radiotherapy following mastectomy is indicated only in the presence of adverse disease characteristics, patients who did not receive radiotherapy may have survived longer because of especially favorable characteristics, despite of lack of radiotherapy.
“When evaluating rare late effects for which sufficient randomized evidence cannot reasonably be obtained, analyses of observational data comparing treated and untreated patients may often be the only source of information, but they must always be interpreted with considerable caution,” wrote the investigators.