Cancer in systemic sclerosis: clinical associations and prognostic impact from the EUSTAR registry

BACKGROUND: Cancer represents a major cause of mortality in systemic sclerosis (SSc). Established risk factors are limited to specific subsets, particularly early diffuse anti-RNA polymerase III (POLR3)-positive disease, needing further exploration. METHODS: We performed a nested case-control study within EUSTAR: cases were SSc patients developing cancer at any timepoint; controls were cancer-free SSc matched for age and disease duration. Malignancies were classified as synchronous to SSc onset (±3 years), subsequent (>3 years after), or previous (>3 years before). Clinical, serological, treatments associations, and survival were analyzed. RESULTS: 454 SSc patients with cancer (29% synchronous, 51% subsequent, 20% previous), and 454 controls were identified. Mean age was 55±13 years, disease duration 5±2 years; 88% were female, 27.5% diffuse SSc; 30.5% had interstitial lung disease (ILD), 32% anti-topoisomerase, 10% anti-POLR3. Synchronous cancers were associated with anti-POLR3 (OR 2.06, 95%CI 1.13-3.69), U1RNP (OR 3.56, 1.03-12.3), smoking (OR 1.57, 1.01-2.44), but negatively with digital ulcers (OR 0.55, 0.31-0.93). Calcinosis was inversely associated with subsequent cancers (OR 0.42, 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, 1.12-3.54), anti-topoisomerase (OR 2.61, 1.38-5.04), and smoking. Cancers occurred more frequently in cyclophosphamide-treated patients. Malignancy worsened overall survival, particularly when subsequent. Radiation therapy did not impact mortality or new-onset ILD. CONCLUSIONS: Cancer timing and site identify distinct clinical-serological associations in SSc, with different prognostic implications. As cancers diagnosed during follow-up are major determinants of mortality, our findings inform the implementation of stratified cancer surveillance in SSc.

Authors

Institutions

Publication Details

Journal
Arthritis & Rheumatology
Published
2026-08-28
DOI
https://doi.org/10.1002/art.70303
Primary Topic
Systemic Sclerosis and Related Diseases
Type
article
Field-Weighted Citation Impact
0.00

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
article

Cancer in systemic sclerosis: clinical associations and prognostic impact from the EUSTAR registry

Francesca Motta, C. Sieiro Santos, S. Blaise, Gonçalo Boleto et al.
Arthritis & Rheumatology
Systemic Sclerosis and Related Diseases
article

Cancer in systemic sclerosis: clinical associations and prognostic impact from the EUSTAR registry

Francesca Motta, C. Sieiro Santos, S. Blaise, Gonçalo Boleto, Fabio Cacciapaglia, Florenzo Iannone, Antonio Tonutti, Maurizio Cutolo, Francesco Benvenuti, Barbara Gabrielli, Elena Rezuş, Beatrice Moccaldi, Duygu Temiz Karadağ, Liala Moschetti, Massimiliano Limonta, Stefano Stano, Luca Idolazzi, Leïla Caillault, Rossella De Angelis, Francesca Nava, Carina Mihai, Claudia Iannone, Nicoletta Del Papa, Stefano Erba, Maria De Santis, Masataka Kuwana, Francesca Romana Di Ciommo, Elisabetta Zanatta, C. Barison, Dóra Tari, L. Núñez, Anastasiia Kozlova, Carlo Selmi, Rahma A. Elziaty, Eleonora Pazzi, Alejandro Brigante, Andrea Benini, Radim Bečvář, Brigitte Granel, Maria Rosa Pellico, Roberta Foti, Roberto Giacomelli, Fabiola Atzeni, Cosimo Bruni, Gabriella Szűcs, Serena Guiducci, Kurszán Jász Dávid, Valeria Riccieri, Ágnes Ágoston‐Szabó, Britta Maurer, Gianluca Moroncini, Gábor Kumánovics, Yuri Sasaki
article en

Abstract

BACKGROUND: Cancer represents a major cause of mortality in systemic sclerosis (SSc). Established risk factors are limited to specific subsets, particularly early diffuse anti-RNA polymerase III (POLR3)-positive disease, needing further exploration. METHODS: We performed a nested case-control study within EUSTAR: cases were SSc patients developing cancer at any timepoint; controls were cancer-free SSc matched for age and disease duration. Malignancies were classified as synchronous to SSc onset (±3 years), subsequent (>3 years after), or previous (>3 years before). Clinical, serological, treatments associations, and survival were analyzed. RESULTS: 454 SSc patients with cancer (29% synchronous, 51% subsequent, 20% previous), and 454 controls were identified. Mean age was 55±13 years, disease duration 5±2 years; 88% were female, 27.5% diffuse SSc; 30.5% had interstitial lung disease (ILD), 32% anti-topoisomerase, 10% anti-POLR3. Synchronous cancers were associated with anti-POLR3 (OR 2.06, 95%CI 1.13-3.69), U1RNP (OR 3.56, 1.03-12.3), smoking (OR 1.57, 1.01-2.44), but negatively with digital ulcers (OR 0.55, 0.31-0.93). Calcinosis was inversely associated with subsequent cancers (OR 0.42, 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, 1.12-3.54), anti-topoisomerase (OR 2.61, 1.38-5.04), and smoking. Cancers occurred more frequently in cyclophosphamide-treated patients. Malignancy worsened overall survival, particularly when subsequent. Radiation therapy did not impact mortality or new-onset ILD. CONCLUSIONS: Cancer timing and site identify distinct clinical-serological associations in SSc, with different prognostic implications. As cancers diagnosed during follow-up are major determinants of mortality, our findings inform the implementation of stratified cancer surveillance in SSc.

Arthritis & Rheumatology
Ain Shams University (EG), University of Messina (IT), University of Verona (IT), Marche Polytechnic University (IT), Libera Università Maria SS. Assunta (IT), University of Debrecen (HU), Humanitas University (IT), University of Padua (IT), University of Lisbon (PT), Inserm (FR), Università Campus Bio-Medico (IT), Universidad Autónoma de la Ciudad de México (MX), University of Zurich (CH), Charles University (CZ), Aix-Marseille Université (FR), University Hospital of Bern (CH), Grigore T. Popa University of Medicine and Pharmacy (RO), Assistance Publique Hôpitaux de Marseille (FR), Hospital Son Llatzer (ES), Institute of Rheumatology (CZ), University Hospital of Zurich (CH), Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT), Ospedale Papa Giovanni XXIII (IT), Istituto Ortopedico Gaetano Pini (IT), Hôpital Nord (FR), Azienda Ospedaliero-Universitaria Careggi (IT), Policlinico Universitario di Catania (IT), Campus Bio Medico University Hospital (IT), Hospital de Santa Maria (PT), Ospedale San Bortolo (IT), Centre Hospitalier Universitaire de Rennes (FR), IRCCS Humanitas Research Hospital (IT), Complejo Asistencial Universitario de Palencia (ES), Kocaeli Üniversitesi (TR), University of Bari Aldo Moro (IT), University of Pecs (HU), University of Brescia (IT), Nippon Medical School (JP), University of Genoa (IT), Sapienza University of Rome (IT), Université Grenoble Alpes (FR)
Ministero della Salute, Humanitas Research Hospital
Good health and well-being
Openalex Percentile: Top 11%
Systemic Sclerosis and Related Diseases
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.