Volume of Systemic Cancer Therapy Delivery and Outcomes of Patients with Solid Tumors: A Systematic Review and Methodologic Evaluation of the Literature

Abstract Background Patients undergoing complex cancer surgery have better outcomes when care is provided by high-volume surgeons and hospitals. It is not known whether this volume-outcome relationship extends to the systemic treatment of solid tumors. Methods MEDLINE, EMBASE, Cochrane Databases, Google Scholar and the online proceedings of ASCO and ESMO were searched up to October 2018. Elements of the scoring system proposed by Institute of Medicine to evaluate volume-outcome studies were used to evaluate the methodologic rigor of the literature. Results Sixteen studies involving 441,890 patients were included. Cancer sites evaluated were testicular (N = 7), lung (N = 2), melanoma (N = 2), renal cell (N = 2), pancreas (n = 1), esophagogastric (N = 1), and cholangiocarcinoma (N = 1). Most studies adjusted for age and stage of disease (N = 14), but few did so for patient comorbidities (N = 7) or performance status (N = 1). Most studies evaluated volume as a categorical variable (N = 13) and used single-level regression (N = 11). No study provided an estimate of the relative contribution of volume to the variance in survival observed. Fourteen of 16 studies concluded that increasing volume was associated with better survival. The unadjusted, absolute improvement comparing the lowest to highest volume categories ranged from 1% to 24%. Conclusion The available evidence suggests that volume of systemic therapy provision for solid tumors may be associated with improved survival. However, each study identified in this review contains such considerable methodologic shortcomings and/or unresolved confounding that estimation of an unbiased treatment effect is not possible. High quality research is needed prior to implementation of volume-based regionalization policies for systemic therapy.