Paradoxical Emergence of Cutaneous Squamous Cell Carcinoma During Pembrolizumab Treatment for Non-muscle Invasive Bladder Cancer and Subsequent Successful Therapeutic Adjustments

Pembrolizumab is a well-established immune checkpoint inhibitor option for patients with locally advanced or metastatic urothelial cell carcinoma and has had emerging use in the treatment of bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC). Additionally, it is a preferred treatment option in patients with unresectable cutaneous squamous cell carcinoma (cSCC). Here, we present a 73-year-old patient with BCG-unresponsive NMIBC treated with pembrolizumab and intravesical gemcitabine who developed a locally advanced cSCC of the lower extremity. The emergence of cSCC during the initial treatment regimen for NMIBC was notable given that the patient lacked traditional risk factors for cSCC and since pembrolizumab is indicated for the management of both cancers. Therapeutic adjustments were made to address the new cSCC, with pembrolizumab being discontinued and replaced with cetuximab. The new regimen was tolerated well, and follow-up over the next year demonstrated the resolution of the cSCC following these changes. In addition to highlighting the rare possibility of a secondary malignancy arising as an adverse event, this report underscores the importance of early identification and individualized therapeutic adjustments for optimizing patient outcomes.