To the Editor:

Shah et al.1 summarize the epidemiology, pathogenesis, and clinical features of extramammary Paget’s disease (EMPD). Given the increased risk of associated internal malignancies among EMPD patients, the authors emphasize the importance of comprehensive cancer screening within this population. Indeed, several authors, using data from the Surveillance, Epidemiology, and End Results (SEER) program, have shown elevated risk of various visceral malignancies, including breast, colorectal, gastric, and prostate cancers.2-4 However, these investigators have also acknowledged that the elevated risk of internal malignancies may in part be due to heightened surveillance in the EMPD post-diagnosis period and the detection of low-grade, indolent neoplasms of unclear clinical significance. At present, the risk of mortality from visceral neoplasms in EMPD remains poorly studied. To bridge this knowledge gap and better inform screening guidelines, we sought to identify the mortality risk from internal malignancies in EMPD patients using data from SEER-17 (2000-2021).

We extracted mortality data on 3,723 EMPD patients using the International Classification of Diseases for Oncology (ICD-O-3) codes 8542/2 and 8542/3 (Table I). Observed (O) number of deaths due to specific malignancies in the EMPD cohort were compared against the expected (E) number of deaths due to these malignancies in an age, race, sex, and calendar-year of death matched control group. Standardized mortality ratios (SMRs) were developed as the O:E ratio at 95% confidence intervals (CIs). Excess absolute risks (EARs) per 10,000 person-years were also computed. We observed 814 deaths in the EMPD cohort, with 272 deaths being attributable to any malignant neoplasm, representing a SMR of 2.08 (95% CI 1.84-2.34) and EAR of 87.82.

Specifically, patients with EMPD exhibited significantly increased mortality rates from breast (SMR 2.62, 95% CI 1.73-3.82) and colorectal (SMR 1.83, 95% CI 1.14-2.76) cancers. Of note, however, we did not detect a significant increase in mortality from bladder (SMR 0.50, 95% CI 0.06-1.81), prostate (SMR 0.46, 95% CI 0.10-1.36), or gastric (SMR 1.54, 95% CI 0.19-5.57)malignancies. Melanoma, which was previously identified as an associated malignancy in EMPD2, was not responsible for any deaths in our EMPD cohort (Table II).

Our study lends further support to current clinical practice guidelines for EMPD.5 Our finding of increased mortality from breast and colorectal cancers is consistent with the current guidelines encouraging vigilant age-appropriate colonoscopy and mammography in EMPD patients. Moreover, although recent studies have found increased rates of bladder and prostate neoplasms in EMPD patients,2-4 we did not observe these malignancies to bear a concomitantly elevated mortality risk. This also aligns with current recommendations against universal prostate cancer or bladder cancer screening in EMPD patients via prostate specific antigen or cystoscopy.5

Our analysis is subject to limitations. Despite quality control measures within SEER, misclassification remains a possibility. Additionally, we are unable to control for lifestyle or socioeconomic factors which may impact mortality from visceral malignancies. Novel findings of our analysis include increased risk of mortality from only breast and colorectal malignancies and no increased risk of mortality from other visceral neoplasms that have been previously described in association with EMPD.

References

1. Shah RR, Shah K, Wilson BN, et al. Extramammary Paget Disease. Part I. Epidemiology, Pathogenesis, Clinical Features, and Diagnosis. J Am Acad Dermatol. doi: 10.1016/j.jaad.2023.07.1051

2. Kilts TP, Long B, Glasgow AE, Bakkum-Gamez JN, Habermann EB, Cliby WA. Invasive vulvar extramammary Paget's disease in the United States. Gynecol Oncol. 2020;157(3):649-655. doi: 10.1016/j.ygyno.2020.03.018.

3. Maloney NJ, Yao H, Aasi SZ, et al. Elevated Risk of Visceral Malignant Neoplasms in Extramammary Paget Disease. JAMA Dermatol. 2023;159(10):1139-1141. doi: 10.1001/jamadermatol.2023.2679

4. Karam A, Dorigo O. Increased risk and pattern of secondary malignancies in patients with invasive extramammary Paget disease. Br J Dermatol. 2014;170(3):661-71. doi: 10.1111/bjd.12635

5. Kibbi N, Owen JL, Worley B, et al. Evidence-Based Clinical Practice Guidelines for Extramammary Paget Disease. JAMA Oncol. 2022;8(4):618-628. doi: 10.1001/jamaoncol.2021.7148. PMID: 35050310