Background: Classification systems may be useful to direct more aggressive treatment to cancer patients with a relatively poor prognosis. The definition of 'poor prognosis' often lacks a formal basis. We propose a decision analytic approach to weigh benefits and harms explicitly to define the treatment threshold for more aggressive treatment. This approach is illustrated by a case study in advanced testicular cancer, where patients with a high risk of mortality under standard treatment may be eligible for high-dose chemotherapy with stem cell support, which is currently defined by the IGCC classification.
Methods: We used published literature to estimate the benefit and harm of high-dose chemotherapy (HD-CT) versus standard-dose chemotherapy (SD-CT) for patients with advanced non-seminomatous germ cell cancer. Benefit and harm were defined as the reduction and increase in absolute risk of mortality due to HD-CT respectively. Harm included early and late treatment related death, and treatment related morbidity (weighted by 'utility').
Results: We considered a conservative and an optimistic benefit of 30 and 40% risk reduction respectively. We estimated the excess treatment related mortality at 2%. When treatment related morbidity was taken into account, the harm of HD-CT increased to 5%. With a relative benefit of 30% and harm of 2 or 5%, HD-CT might be beneficial for patients with over 7 or 17% risk of cancer specific mortality with SD chemotherapy, while with a relative benefit of 40% HD-CT was beneficial over 5 and 12.5% risk respectively. Compared to the IGCC classification 14% of the patients would receive more aggressive treatment, and 2% less intensive treatment.
Conclusion: Benefit and harm can be used to define 'poor prognosis' explicitly for non-seminomatous germ cell cancer patients who are considered for high-dose chemotherapy. This approach can readily be adapted to new results and extended to other cancers to define candidates for more aggressive treatments.