Accuracy of the online prognostication tools PREDICT and Adjuvant! for early-stage breast cancer patients younger than 50 years
Engelhardt, Ellen G.; van den Broek, Alexandra J.; Linn, Sabine C.; Wishart, Gordon C.; Rutgers, Emiel J. Th.; van de Velde, Anthonie O.; Smit, Vincent T.H.B.M.; Voogd, Adri C.; Siesling, Sabine; Brinkhuis, Mariël; Seynaeve, Caroline; Westenend, Pieter J.; Stiggelbout, Anne M; Tollenaar, Rob A E M; van Leeuwen, Flora E.; van 't Veer, Laura J; Ravdin, Peter M.; Pharaoh, Paul D.P.; Schmidt, Marjanka K.
(2017) European Journal of Cancer, volume 78, pp. 37 - 44
(Article)
Abstract
Importance Online prognostication tools such as PREDICT and Adjuvant! are increasingly used in clinical practice by oncologists to inform patients and guide treatment decisions about adjuvant systemic therapy. However, their validity for young breast cancer patients is debated. Objective To assess first, the prognostic accuracy of PREDICT's and Adjuvant! 10-year
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all-cause mortality, and second, its breast cancer–specific mortality estimates, in a large cohort of breast cancer patients diagnosed <50 years. Design Hospital-based cohort. Setting General and cancer hospitals. Participants A consecutive series of 2710 patients without a prior history of cancer, diagnosed between 1990 and 2000 with unilateral stage I–III breast cancer aged <50 years. Main outcome measures Calibration and discriminatory accuracy, measured with C-statistics, of estimated 10-year all-cause and breast cancer–specific mortality. Results Overall, PREDICT's calibration for all-cause mortality was good (predicted versus observed) meandifference: −1.1% (95%CI: −3.2%–0.9%; P = 0.28). PREDICT tended to underestimate all-cause mortality in good prognosis subgroups (range meandifference: −2.9% to −4.8%), overestimated all-cause mortality in poor prognosis subgroups (range meandifference: 2.6%–9.4%) and underestimated survival in patients < 35 by −6.6%. Overall, PREDICT overestimated breast cancer–specific mortality by 3.2% (95%CI: 0.8%–5.6%; P = 0.007); and also overestimated it seemingly indiscriminately in numerous subgroups (range meandifference: 3.2%–14.1%). Calibration was poor in the cohort of patients with the lowest and those with the highest mortality probabilities. Discriminatory accuracy was moderate-to-good for all-cause mortality in PREDICT (0.71 [95%CI: 0.68 to 0.73]), and the results were similar for breast cancer–specific mortality. Adjuvant!'s calibration and discriminatory accuracy for both all-cause and breast cancer–specific mortality were in line with PREDICT's findings. Conclusions Although imprecise at the extremes, PREDICT's estimates of 10-year all-cause mortality seem reasonably sound for breast cancer patients <50 years; Adjuvant! findings were similar. Prognostication tools should be used with caution due to the intrinsic variability of their estimates, and because the threshold to discuss adjuvant systemic treatment is low. Thus, seemingly insignificant mortality overestimations or underestimations of a few percentages can significantly impact treatment decision-making.
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Keywords: Adjuvant!, Breast cancer, PREDICT, Prognostic accuracy, Prognostication tool, Young patients, Oncology, Cancer Research, Journal Article, Evaluation Studies, Multicenter Study
ISSN: 0959-8049
Publisher: Elsevier Limited
Note: Funding Information: The study was funded by the Dutch Cancer Society (DCS) grant numbers DCS-NKI 2001-2423 and DCS-NKI 2007-3839; and by notary office Spier & Hazenberg for the coding procedure. M.K. Schmidt was funded by cancer research award DCS-NKI 2009-4363. E.G. Engelhardt was funded by DCS-UL2010-4805. The funding organisations had no influence on the design and conduct of the study; collection, management, analysis?and interpretation of the data; preparation, review?or approval of the manuscript; and decision to submit the manuscript for publication. Publisher Copyright: © 2017 Elsevier Ltd
(Peer reviewed)