Multiple Primary Malignancies In Patients With Anal Squamous Cell Carcinoma

The 8-year updated results of RTOG-0529 reported that 5/52 patients developed second primary malignancies (SPMs), of which 4/5 died of the SPM. Prior studies examining risk of SPM after a first primary cancer generally use large datasets such as the SEER registry and exclude survivors of previous primaries and developers of synchronous primaries. The goal of this study was to provide a more complete representation of multiple cancer risk in squamous cell carcinoma of the anus (SCCA) patients. A single-institution retrospective review of 46 patients treated definitively for SCCA between January 2006 and July 2017 was conducted. Patients received definitive chemoradiotherapy, except one patient who received curative local excision. An “index primary malignancy” (IPM) was defined as the first diagnosed cancer. A “second primary malignancy” was defined as a biopsy-confirmed distinct primary cancer that developed after diagnosis of an IPM. Patients were classified into one of three groups: prior IPM before SCCA, SCCA only, and SPM after an index SCCA. Univariate logistic regression was used to assess associations between baseline characteristics and multiple primary malignancy status. Overall survival was estimated with the Kaplan-Meier method. Of 46 patients, 18 (39.2%) had either an IPM before SCCA (n = 9) or SPM after an index SCCA (n = 9). Six patients had ≥3 total malignancies. No baseline characteristics (age, gender, race, stage, smoking status) correlated with presence of ≥2 malignancies (among all patients) or development of an SPM (among index SCCA patients). The most common prior IPMs were breast (n = 4) and gynecologic cancers (endometrial (n = 2) and vulvar (n = 1)). Radiotherapy was not used as treatment for malignancies in the pelvic radiation field (gynecological and rectal); other IPMs were outside of the field, so subsequent development of SCCA was not clearly related to radiotherapy. The SPMs were neither found to be in the radiation field nor HPV-related cancers. Of the 9 patients who developed SPMs, 6 (67%) developed lung cancers. Three of these patients had no smoking history, of which 2 developed multiple primary lung cancers. In our cohort, patients without SPMs tended to die from SCCA recurrence, while those with SPMs were more likely to die from their SPM than from SCCA. Our study suggests that patients with SCCA are often either survivors of previous cancers or develop later malignancies. These patients require lifelong surveillance given their elevated risk of malignancy. Future work should focus on identifying genetic or immunologic factors that may predispose SCCA patients to develop multiple primary malignancies.