Malignancies in Patients with Anti-RNA Polymerase III Antibodies and Systemic Sclerosis: Analysis of the EULAR Scleroderma Trials and Research Cohort and Possible Recommendations for Screening

Abstract

Anti-RNAP3+ patients with SSc have a high risk of concomitant malignancy. These results have implications for clinical practice and suggest regular screening for cancer in anti-RNAP3+ patients.

Mechanistic and clinical insights at the scleroderma-cancer interface

“…The frequency of malignancies diagnosed within 6 months before to 12 months after scleroderma onset was also higher in patients with RNA polymerase III autoantibodies (13.6% vs 0% in anti-topoisomerase 1 (p<0.01) and 0.7% in anti-centromere (p<0.01)). Lastly, this relationship was validated in the EUSTAR cohort (65); the authors examined 158 anti-RNA polymerase III-positive patients compared with 199 anti-RNA polymerase III-negative controls, matched on age at scleroderma onset, sex, cutaneous subtype and disease duration. Malignancies were more commonly diagnosed in patients positive for anti-RNA polymerase III antibodies (17.7% vs 9.0%, p=0.015).…”

A To-Do List at Diagnosis of Systemic Sclerosis with Positive Anti-RNA Polymerase III Antibodies

“…In this regard, we have to appreciate a relatively low prevalence of concomitant cancer (~10%) at diagnosis in anti-RNAP III-positive patients with SSc, and consider invasiveness and radiation exposure of screening tests as well as economic issues. In this case, cancer risks identified by Lazzaroni's study may help in clinical practice to institute appropriate cancer screening 19 . Specifically, recommendations for screening of synchronous cancer in anti-RNAP III-positive patients with SSc are proposed using a Delphi exercise by the EUSTAR experts 19 .…”

“…In this case, cancer risks identified by Lazzaroni's study may help in clinical practice to institute appropriate cancer screening 19 . Specifically, recommendations for screening of synchronous cancer in anti-RNAP III-positive patients with SSc are proposed using a Delphi exercise by the EUSTAR experts 19 . These include screening for breast cancer in all female patients, and non-invasive tests guided by clinical suspicion and patient age for other malignancies for all patients.…”

“…As expected, multivariate analysis identified SRC, GAVE, rapid progression of skin thickness, and malignancies concomitant to SSc onset as independent characteristics associated with anti-RNAP III antibodies, although the association with pulmonary hypertension was not confirmed. In addition, Lazzaroni's study has provided valuable information on cancer development in patients with SSc who have anti-RNAP III antibodies, including that (1) the majority of cancer was diagnosed within an interval between 6 months before and 12 months after SSc onset; (2) the most prevalent cancer type was breast cancer, (3) patients with older age or dcSSc were particularly at risk, and (4) malignancies other than breast cancer were much more frequent in males 19 . Nevertheless, frequency of cancer diagnosis within 2 years before or after SSc onset in anti-RNAP III-positive patients was only 11%, and the number of anti-RNAP III-positive patients needed to screen to find 1 synchronous cancer at SSc diagnosis was about 17.…”

“…In this issue of The Journal, Lazzaroni, et al examined characteristics of anti-RNAP III-positive patients with SSc using the European Scleroderma Trials and Research (EUSTAR) registry, the largest multicenter cohort of patients with SSc 19 . Especially, a case-control study strategy involving anti-RNAP III-positive and -negative patients with SSc matched for sex, disease duration, disease subset, and age at disease onset was useful in eliminating potential influences of confounding factors.…”