Discrepancy in PD-L1 expression between primary and metastatic tumors in two patients with recurrent cervical cancer.

Introduction: Pembrolizumab is an immunotherapy approved for use in patients with a combined positive score (CPS) greater than one with recurrent cervical cancer. In clinical practice, the CPS score is not typically analyzed in both primary and metastatic specimens.

Case Descriptions: Case 1A 42-year-old woman with history of an abnormal pap smears who presented with a large pelvic mass with initial biopsy of cervix demonstrating squamous cell carcinoma with negative PDL1 expression and a CPS score of 0. She underwent chemoradiation and presented three months after primary treatment completion with recurrence of squamous cell carcinoma and positive PD-L1 expression with a CPS score of 20. Pembrolizumab was added to cycle three of her systemic chemotherapy regimen of carboplatin/paclitaxel/bevacizumab. She had progression on this regimen and was transitioned to tisotumab vedotin; however, ultimately opted to proceed with hospice secondary to failure to thrive.Case 2A 36-year-old woman with history of an abnormal pap smear in pregnancy and initial biopsy demonstrating endocervical adenocarcinoma, mucinous type. She underwent open radical hysterectomy, bilateral salpingectomy, bilateral oophorepexy, and bilateral pelvic lymph node dissection with subsequent adjuvant chemoradiation. Her initial pathology demonstrated positive PDL1 expression with CPS score of 15. She presented six months after completion of primary treatment with recurrence of endocervical adenocarcinoma, mucinous type and negative PD-L1 expression with a CPS score of < 1. Regardless of this discrepancy, pembrolizumab was added to cycle five of her systemic chemotherapy regimen of carboplatin/paclitaxel/bevacizumab. She initially demonstrated a mixed response; however, ultimately progressed after eight cycles and was transitioned to tisotumab vedotin.

Discussion: To our knowledge, discrepancies in PD-L1 expression in a matched setting between primary and metastatic tumors has only been reported once. This is the first case report describing these inconsistencies. Etiologies of and outcomes related to the discrepant expression of PD-L1 should be further studied.