Cancer in Systemic Sclerosis: Clinical Associations and Prognostic Impact From the EUSTAR Registry.
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Tonutti Antonio, Motta Francesca, Moschetti Liala, Bruni Cosimo, Mihai Carina, Iannone Claudia, Pellico Maria Rosa, Stano Stefano, Erba Stefano, Barison Claudia, Pazzi Eleonora, Benini Andrea, Moccaldi Beatrice, Dávid Kurszán Jász, Ágoston-Szabó Ágnes, Gabrielli Beatrice, Nava Francesca, Tari Dóra, Di Ciommo Francesca Romana, Sasaki Yuri, Boleto Gonçalo, Bečvář Radim, Brigante Alejandro, Maurer Britta, Limonta Massimiliano, Elziaty Rahma A, Atzeni Fabiola, López Núñez Lilian Maria, Foti Roberta, Benvenuti Francesco, Granel Brigitte, Rezus Elena, Caillault Leila, Blaise Sophie, Sieiro Santos Cristiana, Cacciapaglia Fabio, Giacomelli Roberto, De Angelis Rossella, Guiducci Serena, Temiz Karadag Duygu, Szűcs Gabriella, Idolazzi Luca, Kumánovics Gábor, Iannone Florenzo, Cutolo Maurizio, Moroncini Gianluca, Riccieri Valeria, Del Papa Nicoletta, Zanatta Elisabetta, Distler Oliver, Kuwana Masataka, Selmi Carlo, De Santis Maria
Аннотация
METHODS: We performed a nested case-control study within the European Scleroderma Trials and Research group: "cases" were defined as patients with SSc who developed cancer at any time point; controls were patients with SSc who were cancer free, matched for age and disease duration. Malignancies were classified as "synchronous" to SSc onset (±3 years), "subsequent" (more than three years after), or "previous" (more than three years before). Clinical, serologic, and treatment associations, as well as survival rates, were analyzed.
RESULTS: A total of 454 patients with SSc with cancer (29% synchronous, 51% subsequent, 20% previous) and 454 controls were identified. Mean age was 55 ± 13 years, disease duration was 5 ± 2 years; 88% were female, and 27.5% had diffuse SSc; 30.5% had interstitial lung disease (ILD), 32% had anti-topoisomerase, and 10% had anti-POLR3. Synchronous cancers were associated with anti-POLR3 (odds ratio [OR] 2.06, 95% confidence interval [CI] 1.13-3.69), U1RNP (OR 3.56, 95% CI 1.03-12.3), and smoking (OR 1.57, 95% CI 1.01-2.44), but they were negatively associated with digital ulcers (OR 0.55, 95% CI 0.31-0.93). Calcinosis was inversely associated with subsequent cancers (OR 0.42, 95% CI 0.17-0.93). Breast cancer showed time-dependent associations with anti-POLR3 and anti-PM/Scl; lung cancer was mainly subsequent and associated with ILD (OR 2.00, 95% CI 1.12-3.54), anti-topoisomerase (OR 2.61, 95% CI 1.38-5.04), and smoking. Cancers occurred more frequently in patients treated with cyclophosphamide. Malignancy worsened overall survival, particularly when subsequent. Radiation therapy did not impact mortality rate or new-onset ILD.
CONCLUSION: Cancer timing and site identify distinct clinical-serologic associations in SSc, with different prognostic implications. As cancers diagnosed during follow-up are major determinants of death, our findings inform the implementation of stratified cancer surveillance in SSc.