How do we estimate survival? External validation of a tool for survival estimation in patients with metastatic bone disease—decision analysis and comparison of three international patient populations

Andrea Piccioli, M. Silvia Spinelli, Jonathan A. Forsberg, Rikard Wedin, John H. Healey, Vincenzo Ippolito, Primo Andrea Daolio, Pietro Ruggieri, Giulio Maccauro, Alessandro Gasbarrini, Roberto Biagini, Raimondo Piana, Flavio Fazioli, Alessandro Luzzati, Alberto Di Martino, Francesco Nicolosi, Francesco Camnasio, Michele Attilio Rosa, Domenico Andrea Campanacci, Vincenzo Denaro, Rodolfo Capanna

We recently developed a clinical decision support tool, capable of estimating the likelihood of survival at 3 and 12 months following surgery for patients with operable skeletal metastases. After making it publicly available on www.PATHFx.org , we attempted to externally validate it using independent, international data. We collected data from patients treated at 13 Italian orthopaedic oncology referral centers between 2010 and 2013, then applied to PATHFx, which generated a probability of survival at three and 12-months for each patient. We assessed accuracy using the area under the receiver-operating characteristic curve (AUC), clinical utility using Decision Curve Analysis (DCA), and compared the Italian patient data to the training set (United States) and first external validation set (Scandinavia). The Italian dataset contained 287 records with at least 12 months follow-up information. The AUCs for the three-month and 12-month estimates was 0.80 and 0.77, respectively. There were missing data, including the surgeon's estimate of survival that was missing in the majority of records. Physiologically, Italian patients were similar to patients in the training and first validation sets. However notable differences were observed in the proportion of those surviving three and 12-months, suggesting differences in referral patterns and perhaps indications for surgery. PATHFx was successfully validated in an Italian dataset containing missing data. This study demonstrates its broad applicability to European patients, even in centers with differing treatment philosophies from those previously studied.