Extramammary Paget's disease (EMPD) is a malignant skin tumor that develops on the skin rich in apocrine glands. Chemotherapy using cytotoxic anticancer agents, such as docetaxel or 5-fluorouracil and cisplatin has been administered for advanced EMPD. However, no comparative studies of regimens or results from published prospective studies exist, and no standard treatment has been established. Nivolumab, an immune checkpoint inhibitor, was approved in Japan in February 2024 for unresectable advanced or recurrent epithelial skin malignancies, including EMPD. This approval was based on the results of a domestic Phase II trial, where the response rate for EMPD was 25% (1/4 cases) 1. We report a case of reduced multiple lymph node metastases following nivolumab treatment. An 80-year-old male patient presented with erythema on his lower abdomen that had persisted for 5 months. EMPD was diagnosed using skin biopsy. Clinical findings included an 8 × 7 cm erythematous patch in the lower abdomen, with a nodular lesion. Computed tomography (CT) revealed enlarged lymph nodes in the inguinal, pelvic, and para-aortic areas (Figure 1a–c). Surgical treatment was deemed difficult, and systemic therapy with nivolumab (480 mg/body weight every 4 weeks) was initiated. After completing 5 cycles of nivolumab, CT showed reduction in most lymph node metastases, leading to a partial response (Figure 1d–f). CT performed after 9 cycles revealed a reduction in the size of the bilateral inguinal and external iliac lymph nodes; however, enlargement of the obturator, common iliac, and para-aortic lymph nodes was noted (Figure 1g–i). Additionally, imaging revealed findings suggestive of drug-induced pneumonia. Therefore, nivolumab was discontinued. Radiation therapy was planned for enlarged lymph nodes. Before the approval of nivolumab, no drug therapy with insurance coverage existed for EMPD in Japan. However, pembrolizumab, an anti-programmed cell death protein 1 antibody, has been approved for treating solid tumors with high tumor mutational burden (TMB) and microsatellite instability (MSI). A few cases in which pembrolizumab was effective for advanced EMPD with high TMB have been reported 2, 3. In this case, because the tumor cellularity in the biopsy specimen was low, genomic testing was performed using FoundationOne Liquid CDx. The results indicated a tumor mutational burden (TMB) of 0 muts/Mb, a circulating tumor DNA (ctDNA) tumor fraction of < 1.0%, and microsatellite stability (MSS). However, each of these measures has inherent limitations in accurately characterizing the tumor itself. Nonetheless, even in the absence of well-established predictive biomarkers, partial responses to combined nivolumab plus ipilimumab therapy with a duration of up to 7 months have been reported 4. These observations suggest that molecular metrics alone may be insufficient to fully predict responsiveness to immune checkpoint inhibitors. This case highlights nivolumab efficacy against multiple lymph node metastases in patients with EMPD. Currently, no other drug therapies have been approved for EMPD besides nivolumab, making it the first-line choice; however, evidence regarding its efficacy remains insufficient. Therefore, future studies should focus on building evidence for the treatment of EMPD, including biomarker-guided approaches, as well as detailed analyses of large-scale studies examining combination therapy with radiotherapy and sequential treatment with cytotoxic anticancer agents. The authors would like to thank all those who provided valuable input and support throughout the research process. The authors have nothing to report. Approval of the research protocol by an Institutional Reviewer Board: N/A. Written informed consent was obtained from the patient for the publication of this case report and any accompanying images. All personally identifiable information has been anonymized to ensure patient confidentiality. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.
Morioka et al. (Mon,) studied this question.