Advantages of a multi-state approach in surgical research: how intermediate events and risk factor profile affect the prognosis of a patient with locally advanced rectal cancer

• Published in: BMC medical research methodology Vol. 18; no. 1; p. 23
• Main Authors: Manzini, G, Ettrich, T J, Kremer, M, Kornmann, M, Henne-Bruns, D, Eikema, D A, Schlattmann, P, de Wreede, L C
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 13.02.2018; BioMed Central; BMC
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cancer metastasis; Cancer patients; Care and treatment; Chemotherapy; Colorectal cancer; Development and progression; Distant metastasis (DM); Dynamic prediction; Female; Health aspects; Humans; Kaplan-Meier Estimate; Local recurrence (LR); Male; Middle Aged; Multi-state model (msm); Neoplasm Metastasis; Neoplasm Recurrence, Local; Outcome Assessment (Health Care) - methods; Outcome Assessment (Health Care) - statistics & numerical data; Prognosis; Randomized Controlled Trials as Topic; Rectal cancer (RC); Rectal Neoplasms - drug therapy; Rectal Neoplasms - pathology; Rectal Neoplasms - surgery; Risk Assessment - methods; Risk Assessment - statistics & numerical data; Risk Factors; Rectal cancer (RC); Local recurrence (LR); Multi-state model (msm); Distant metastasis (DM); Dynamic prediction
• ISSN: 1471-2288; 1471-2288
• DOI: 10.1186/s12874-018-0476-z

Standard survival analysis fails to give insight into what happens to a patient after a first outcome event (like first relapse of a disease). Multi-state models are a useful tool for analyzing survival data when different treatments and results (intermediate events) can occur. Aim of this study was to implement a multi-state model on data of patients with rectal cancer to illustrate the advantages of multi-state analysis in comparison to standard survival analysis. We re-analyzed data from the RCT FOGT-2 study by using a multi-state model. Based on the results we defined a high and low risk reference patient. Using dynamic prediction, we estimated how the survival probability changes as more information about the clinical history of the patient becomes available. A patient with stage UICC IIIc (vs UICC II) has a higher risk to develop distant metastasis (DM) or both DM and local recurrence (LR) if he/she discontinues chemotherapy within 6 months or between 6 and 12 months, as well as after the completion of 12 months CTx with HR 3.55 (p = 0.026), 5.33 (p = 0.001) and 3.37 (p < 0.001), respectively. He/she also has a higher risk to die after the development of DM (HR 1.72, p = 0.023). Anterior resection vs. abdominoperineal amputation means 63% risk reduction to develop DM or both DM and LR (HR 0.37, p = 0.003) after discontinuation of chemotherapy between 6 and 12 months. After development of LR, a woman has a 4.62 times higher risk to die (p = 0.006). A high risk reference patient has an estimated 43% 5-year survival probability at start of CTx, whereas for a low risk patient this is 79%. After the development of DM 1 year later, the high risk patient has an estimated 5-year survival probability of 11% and the low risk patient one of 21%. Multi-state models help to gain additional insight into the complex events after start of treatment. Dynamic prediction shows how survival probabilities change by progression of the clinical history.