The relationship between progression-free and post-progression survival in treating four types of metastatic cancer

CONTEXT: A number of authors have found that there exists a positive relationship between progression-free survival and overall survival in clinical trials of cancer treatments for particular types of metastatic cancer. However, such an outcome is consistent with an increase in progression-free survival generally leading to an increase, a decrease or no change in survival following disease progression (post-progression survival) and which of these theories is valid has yet to be thoroughly investigated. OBJECTIVE: To test theories of this nature in relation to the use of chemotherapy in treating four different types of metastatic cancer by performing a systematic search of published clinical trials. The four types of metastatic cancer are metastatic breast cancer, colorectal cancer, hormone-refractory prostate cancer and non-small-cell lung cancer. METHODS: The data sources were systematic reviews of randomized controlled trials (RCTs) published between January 1990 and June 2007 that appear in Medline or the Cochrane Database of Systematic Reviews and the abstracts of articles referenced in such reviews. For an RCT to be included in the study, chemotherapy had to be administered to both the treatment and control groups and the chemical composition of the chemotherapy had to be different between the two groups. The median time to disease progression and the median overall survival time had to be reported in the data sources. RESULTS: The trial data found through the systematic search shows much greater support for the theory that, for all four types of metastatic cancer being considered, changes in post-progression survival are uncorrelated with changes in time to disease progression than for the theory that gains in post-progression survival are proportional to gains in time to progression. CONCLUSION: The theories about the relationship between progression-free and post-progression survival in cancer treatment that have been examined in this study are worthy of further investigation.