Compared with the general population, patients with systemic sclerosis (SSc; scleroderma) or inflammatory myopathies, particularly dermatomyositis, may have higher risk for cancer.1
In a presentation at the American College of Rheumatology (ACR) State-of-the-Art Clinical Symposium held virtually in May 2020, Ami Shah, MD, director of Clinical and Translational Research at the Johns Hopkins Scleroderma Center in Baltimore, Maryland, discussed strategies for cancer screening in patients with rheumatic diseases, with an emphasis on scleroderma and dermatomyositis.2
The risk for cancer in patients with dermatomyositis is 4.5-fold greater than the risk in those without dermatomyositis. Cancer risk is elevated in the dermatomyositis population for most site-specific malignancies, including lung, ovarian, breast, colorectal, cervical, bladder, nasopharyngeal, esophageal, pancreatic, colon, and kidney cancers.3 Standardized incidence ratios for cancer in SSc range from 1.24 to 4.20,1 with these patients being at higher risk for lung, bladder, hematologic, liver, esophageal, oropharyngeal, and nonmelanoma skin malignancies.4
The risk for cancer in patients with scleroderma or dermatomyositis is not evenly distributed. Study data from an observational cohort with scleroderma at the Johns Hopkins Scleroderma Center indicated that risk for cancer in this population did not exceed that of the general population. However, cancer risk was significantly elevated in patients with scleroderma who had RNA polymerase III (antipol) or anti-RNPC3 antibodies or those who did not show centromere, topoisomerase 1, and pol antibodies.2,5 Among patients with dermatomyositis, the risk for cancer was found to be highest when antinuclear matrix protein (NXP-2) antibodies or antitranscription intermediary factor 1γ (TIF-1γ) antibodies were present.6
In her address,2 Dr Shah recommended that all patients with new-onset scleroderma or dermatomyositis receive cancer screening based on their age, sex, and considering conventional cancer risk factors, such as smoking or sun exposure. For patients with scleroderma in high risk subgroups, mammography and prostate-specific antigen testing (PSA) were noted to be important, and computed tomography (CT) of the chest, pelvis, and abdomen may be considered. Because of the increased risk for tongue cancer in scleroderma, patients with globus sensation should be referred for ear, nose, and throat evaluation. Patients with dermatomyositis who test positive for TIF-1g or NXP-2 should receive cancer screening based on their age, sex, and risk factors; however, colonoscopy, mammography, and PSA testing should be recommended to patients aged ≥40 years. Chest, abdomen, and pelvis CTs may be considered. Whole-body positron emission tomography (PET)/CT, along with mammography and colonoscopy, can also be considered instead of conventional screening involving multiple tests, particularly for patients with refractory disease. Annual routine screening should be continued.2
In some cases, a rheumatic disease may represent an immunologic response to an internal malignancy. Dr Shah stated in her presentation at the ACR clinical symposium that certain “red flags” in patients with scleroderma or dermatomyositis may signal the presence of underlying cancer. These indicators may include new-onset disease in patients aged >60 years; aggressive, atypical, or treatment unresponsive disease; weight loss or constitutional symptoms out of proportion to disease severity; and a striking personal or family history of cancer.2
Although the evidence is most robust in dermatomyositis and SSc, other rheumatic diseases may also warrant vigilance in cancer screening, according to Christopher Mecoli, MD, MHS, assistant professor of medicine at Johns Hopkins University School of Medicine Division of Rheumatology in Baltimore, Maryland. “In general, many of our diseases can have nebulous or nonspecific symptoms, so malignancy is often on the differential diagnosis. Even once a rheumatic disease is diagnosed, sometimes there is a suspicion of a paraneoplastic process, that is, the cancer may be ‘driving’ the rheumatic disease.”
Evidence-based guidelines for cancer screening and monitoring in rheumatic disease are lacking, though there are several published reviews that provide guidance based on expert opinion.7 Moreover, no rigorous evidence is available yet to show that earlier cancer detection improves outcomes in patients with rheumatic disease.2 “Most experts agree that age- and sex-appropriate screening should be kept up to date, though this guidance may vary based on location/country.
“Even in the US, one could follow the United States Preventive Services Task Force (USPSTF), American Cancer Society (ACS), American College of Obstetricians and Gynecologists, or other guidelines on age- and sex-specific cancer screening; all which have subtle differences,” Dr Mecoli added. “The major questions revolve around what should be done above and beyond this testing. Many rheumatologists obtain a CT scan of the chest, abdomen, and pelvis in the immediate years after symptom onset of diseases such as dermatomyositis. Other testing, such as transvaginal ultrasound for [the detection of] ovarian and endometrial cancer, PSA for prostate cancer, [serum and urine protein electrophoresis] for myeloma/plasma cell dyscrasia, PET/CT, and others are used on a case-by-case basis.”
Dr Mecoli noted that more data are needed to quantify the risk for false negatives and positives, numbers needed to screen, costs, and consequences of cumulative radiation.
The limitations of age and sex cancer screening were demonstrated in a recent analysis of claims data from patients with dermatomyositis and matched control participants. Patients with vs without dermatomyositis had a malignancy frequency of 10.3% vs 5.1%, respectively (P <.0001). Researchers of the study indicated that none of the malignancies that occurred in patients with dermatomyositis aged <50 years of age would have been detected by routine USPSTF or ACS recommended screening.8
According to Dr Mecoli, cancer screening is central to the rheumatologist’s role and falls under the rheumatologist’s purview. “Nonrheumatology providers may not be aware of all the cancer-rheumatic disease associations, so it’s our role to educate [them] and be the drivers of this testing.”
- Cappelli LC, Shah AA. The relationships between cancer and autoimmune rheumatic diseases. Best Pract Res Clin Rheumatol. 2020;34(1):101472.
- Shah, A. Cancer screening in rheumatic diseases. Presented at: American College of Rheumatology State-of-the-Art Clinical Symposium (virtual); May 16-17, 2020.
- Yang Z, Lin F, Qin B, Liang Y, Zhong R. Polymyositis/dermatomyositis and malignancy risk: A metaanalysis study. J Rheumatol. 2015;42(2):282-291.
- Shah AA, Casciola-Rosen L. Cancer and scleroderma: A paraneoplastic disease with implications for malignancy screening. Curr Opin Rheumatol. 2015;27(6):563-570.
- Igusa T, Hummers LK, Visvanathan K, et al. Autoantibodies and scleroderma phenotype define subgroups at high-risk and low-risk for cancer. Ann Rheum Dis. 2018;77(8):1179-1186.
- Fiorentino DF, Chung LS, Christopher-Stine L, et al. Most patients with cancer-associated dermatomyositis have antibodies to nuclear matrix protein NXP-2 or transcription intermediary factor 1γ. Arthritis Rheum. 2013;65(11):2954-2962.
- Selva-O’Callaghan A, Martinez-Gómez X, Trallero-Araguás E, Pinal-Fernández I. The diagnostic work-up of cancer-associated myositis. Curr Opin Rheumatol. 2018;30(6):630-636.
- Kundrick A, Kitts S, Maczuga S, Olsen N, Foulke G. Age- and sex-appropriate cancer screening risks missing most occult malignancies in young patients with dermatomyositis. Br J Dermatol. 2020;182(5):1283-1285.