Bladder cancer (BC) poses a significant health challenge, particularly in metastatic cases, where the prognosis is unfavorable and therapeutic options are limited. Poly ADP-ribose polymerase (PARP) inhibitors have gained approval for use in various cancer types, but their application in BC remains controversial, despite the notable prevalence of DNA damage response alterations in advanced or metastatic urothelial carcinomas. In this report, we describe a 66-year-old heavy-smoking female diagnosed with muscle-invasive BC. She underwent multiple rounds of chemotherapy and radiation, yet her disease remained poorly controlled, leading to metastasis in the left obturator internus muscle. Comprehensive genomic profiling through FoundationOne® Liquid CDx, examining a 324-gene panel using circulating tumor DNA from blood samples, revealed a pathogenic ATM gene alteration (p.Q654fs*10, c.1960delC), suggesting potential eligibility for PARP inhibitor therapy. Remarkably, the patient achieved a complete response to talazoparib, prompting an optimal investigation into BC candidates for this promising therapy.
Keywords: PARP inhibitor; bladder cancer; case report; genetic testing; homologous recombination deficiency; talazoparib.
A new hope for advanced bladder cancer treatment: a case study on the success of PARP inhibitors Bladder cancer is a significant health problem, particularly when it spreads to other parts of the body. The outcome for these advanced cases is often poor and treatment options are limited. One type of treatment, called PARP inhibitors, has shown success in treating other types of cancer, but its use in bladder cancer is still under investigation. This article presents the case of a 66-year-old heavy-smoker woman who was diagnosed with an aggressive form of bladder cancer. Despite several rounds of chemotherapy and radiation, her cancer was not well-controlled and spread to a hip muscle. A detailed genetic analysis revealed specific alterations that suggested she might benefit from treatment with a PARP inhibitor. This type of treatment works by blocking a protein that cancer cells need to repair their DNA, causing the cancer cells to die. The patient was treated with a PARP inhibitor called talazoparib and her cancer completely disappeared with this treatment. This positive response highlights the potential of PARP inhibitors as a promising treatment for bladder cancer, especially in patients who don’t respond to conventional treatments and whose cancer has specific genetic changes. Our study also provides an overview of clinical trials evaluating PARP inhibitors in bladder cancer and summaries reported bladder cancer cases in the literature showing a good response to PARP inhibitors, along with their respective genetic alterations. In conclusion, this case study contributes to the growing understanding of personalized medicine, where treatment is tailored to the specific genetic mutations of each patient’s cancer. It emphasizes the importance of identifying bladder cancer patients who could benefit most from PARP inhibitor therapy, offering a potential lifeline for those who haven’t responded to initial treatment.
© The Author(s), 2024.