Complete response to immune checkpoint inhibitor–combined chemotherapy in recurrent adenosquamous carcinoma of the gallbladder: a case report

Abstract Background Adenosquamous carcinoma of the gallbladder is a rare histologic subtype, accounting for approximately 1–5% of gallbladder cancers. It is considered to have an aggressive biological behavior and a poor prognosis because of its tendency for early recurrence. Although resection remains the only potentially curative treatment, no standard therapy has been established for recurrent disease, and it often shows resistance to systemic chemotherapy. Case presentation A 67-year-old man underwent cholecystectomy with gallbladder bed resection and regional lymphadenectomy for suspected gallbladder cancer. Histopathological examination revealed adenosquamous carcinoma of the gallbladder (pT2bN1M0, pStage IIIB). Postoperatively, he received adjuvant chemotherapy with oral S-1; however, at 4 months after surgery, he developed lung and adrenal metastases and intra-abdominal lymph node recurrence. For the recurrent disease, we initiated first-line systemic therapy for biliary tract cancer with gemcitabine plus cisplatin (GC), in combination with the anti–programmed cell death 1 (PD-1) antibody pembrolizumab. Results After five cycles of therapy, computed tomography demonstrated complete resolution of the lung metastases, marked regression of the adrenal metastasis, and marked shrinkage of the intra-abdominal lymph node lesions, representing a near-complete response. After continued treatment, including maintenance therapy with gemcitabine plus pembrolizumab from cycle 9, follow-up computed tomography after cycle 10 demonstrated complete disappearance of the adrenal metastasis and further regression of the metastatic lymph node to a short-axis diameter of less than 10 mm, fulfilling the RECIST version 1.1 criteria for a complete response (CR). The patient has remained recurrence-free for 16 months after surgery. Conclusions In the field of biliary tract cancer, the efficacy of chemoimmunotherapy incorporating immune checkpoint inhibitors has been increasingly demonstrated; however, current guidelines provide no specific therapeutic recommendations for adenosquamous carcinoma of the gallbladder. In this case, we selected GC combined with pembrolizumab, in accordance with standard treatment for gallbladder cancer, and achieved a CR in the recurrent lesions. Reports of CR to chemoimmunotherapy in recurrent gallbladder adenosquamous carcinoma are extremely limited. Therefore, this case adds valuable evidence suggesting that the addition of immunotherapy may enhance treatment efficacy in this rare and aggressive histologic subtype.