Contributed by Gautam Jha, MD
Until recently, no consensus existed on treatment for patients whose urothelial cancer had progressed on treatment with platinum-based chemotherapy or those who were not candidates for such therapy. Immunotherapy with programmed death cell (PD-1) receptor or its ligand PD-L1 monoclonal antibodies offers these patients another class of therapeutic agents.
A 62-year-old man presented to his physician with hematuria and was treated for presumed recurrent urinary tract infections. Subsequent work-up, including urine cytology, was positive for atypical cells, a concern for malignancy that prompted referral to University of Minnesota Health specialists for further management. The patient had been healthy, although he did report having smoked a half pack of cigarettes a day for the past 30 years.
Diagnosis and Treatment
The patient had cystoscopy and trans-urethral resection of bladder tumor that revealed a high-grade urothelial cancer with muscle invasion, and he was referred to medical oncology. Positron emission tomography (PET) scan to determine cancer stage revealed a nodule in his lung. A biopsy identified it as metastatic urothelial cancer. (See pretreatment scan Figure 1.)
The patient enrolled in a clinical trial that employed a regimen of cisplatin, gemcitabine, and bevacizumab. He had a very good partial response after the initial 9 weeks of chemotherapy, but soon he struggled with low white cell counts and needed several dose reductions and treatment delays as per clinical trial protocol. He received 9 courses of 3 treatments per week over a 6-month period, but disease progression continued. He needed oxycodone for suprapubic pain and had recurrent hematuria. He was switched to docetaxel, but followup scans revealed multiple new pulmonary nodules. At that time, he began treatment with pemetrexed. The patient did not respond to pemetrexed either and had clear clinical and radiographic signs of disease progression, which included new pulmonary nodules and a large osseous metastasis involving the 11th rib.
The patient was treated as an inpatient for perirectal abscess, cellulitis, and fevers. By this time, cancer had progressed on all approved lines of therapy, and he was not sufficiently healthy to tolerate any further chemotherapy. Progressive pain was hard to control with medications.
As an alternative to hospice, he was offered immunotherapy with nivolumab, which was then still beingevaluated in clinical trials for bladder cancer therapy. Tumor cells activate the PD-1 receptor to successfully evade elimination by the immune system. Nivolumab, a monoclonal antibody, blocks this interaction and thus facilitates an anti-tumor immune response. Within weeks of initiation of nivolumab, the patient experienced markedly reduced pain. After 3 months of therapy with nivolumab, he had near complete radiographic response and resolution of all his pain (Figure 2). His treatment was continued for another year and has been held since then. Currently, he remains free of disease and off therapy for over 9 months.
Over the last few years, 5 monoclonal antibodies from the class of PD-1/ PD-L1 inhibitors (nivolumab, atezolizumab, pembrolizumab, durvalumab, and avelumab) have been approved for treating metastatic bladder cancer. These agents are very well tolerated and offer an excellent treatment option for patients whose condition progresses on initial chemotherapy or who are not candidates for chemotherapy.
While chemotherapy is the first-line treatment for advanced urothelial cancer, checkpoint inhibitors have shown success in patients with bladder cancer. Clinical trials are testing their further use.Continue reading