Anti-RNA Polymerase Antibodies Heighten Cancer Risk

Damian McNamara

February 22, 2016

LISBON, Portugal — People with systemic sclerosis who have anti-RNA polymerase III antibodies are at significantly higher risk for certain malignancies, according to a multicenter study from the European Scleroderma Trials and Research Group.

"We found an increased rate of malignancies in positive patients and, in particular, malignancies synchronous to the onset of systemic sclerosis," Maria Grazia Lazzaroni, MD, from the University of Brescia in Italy, said here at the Systemic Sclerosis World Congress 2016.

This result confirms findings from previous smaller trials, but the researchers take it a step further and calculate the number of patients needed to screen to detect each cancer. They also make screening and surveillance recommendations on the basis of their findings.

"Screening for malignancies at the moment of diagnosis in anti-RNA positive patients is highly recommended," added Dr Lazzaroni.

Dr Lazzaroni and her colleagues used the EUSTAR database to identify patients with information on anti-RNA antibody status.

EUSTAR Database Study

When they compared the 176 antibody-positive patients with the 4763 antibody-negative patients, scleroderma renal crisis emerged as a significant risk associated with the anti-RNA antibody (odds ratio [OR], 7.6), as did diffuse cutaneous type sclerosis (OR, 2.35).

To assess the synchronous onset of cancer (within 2 years) and to identify risk factors, the team then conducted a case–control study of 158 antibody-positive patients with 199 antibody-negative control subjects from 13 EUSTAR centers.

The overall risk for cancer was greater in the patients with anti-RNA antibodies than in the control subjects, which is in agreement with data linking the presence of anti-RNA antibodies to an immune response against cancer cells.

The number needed to screen to detect one synchronous malignancy was "quite low," Dr Lazzaroni reported. People with diffuse type systemic sclerosis were more likely to develop a synchronous cancer (93% vs 55%; P = .008). Another significant factor was age; people who developed a synchronous cancer were, on average, older than those with systemic sclerosis who did not develop cancer (65 vs 49 years; P < .001).

Table. Cancer Risk in Antibody-Positive Patients With Early Systemic Sclerosis

Outcome Odds Ratio Number Needed to Screen
Any malignancy 2.17
Synchronous cancer 4.46 15
Breast cancer 20.2 17


Dr Lazzaroni and her colleagues performed a web-based Delphi exercise, sharing their findings with all EUSTAR centers and getting input from 82 experts on recommended screening in everyday practice.

"There was a high level of agreement on screening patients for synchronous malignancies, especially synchronous breast cancers," Dr Lazzaroni said. The team recommends that screening for other malignancies be guided by clinical suspicion and patient age.

Tight surveillance for cancer in the first year after a diagnosis of systemic sclerosis is also recommended.

After the presentation, Dr Lazzaroni was asked whether treating a synchronous breast cancer would improve a patient's systemic sclerosis.

"There is no strong evidence, but in our experience, our patients did not die from the cancer and their survival was quite good," she reported.

However, prospective studies are needed to confirm these findings, she pointed out.

"The new information is how many patients you need to screen to pick up cancer, and it looks like it might not be that many," said session moderator Bashar Kahaleh, MD, from the University of Toledo in Ohio. "Otherwise, this study confirms earlier research regarding synchronous cancers in this population."

But one question remains unanswered, said Armando Gabrielli, MD, from Istituto di Clinica Medica in Ancona, Italy.

"If you're treating a woman with this antibody who you think is at increased risk of cancer, what kind of treatment for systemic sclerosis should you use? Cyclophosphamide could increase the malignancy risk," he told Medscape Medical News. "Patients with vasculitis treated with cyclophosphamide have been shown to be at higher risk for cancer, so more study is needed."

Dr Lazzaroni, Dr Kahaleh, and Dr Gabrielli have disclosed no relevant financial relationships.

Systemic Sclerosis World Congress (SSWC) 2016. Presented February 20, 2016.


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