Q&A: Bladder Cancer Treatment Challenges

Medscape

3 days ago

Kyle A. Richards, MD
Bladder cancer is a prevalent malignancy affecting the urinary system, with symptoms including gross or microscopic hematuria, urinary frequency, and pelvic pain. Medscape spoke with Kyle A. Richards, MD, an associate professor in the Department of Urology at University of Wisconsin School of Medicine and Public Health, about the current challenges in bladder cancer diagnosis and treatment.
What are the challenges with managing early stage bladder cancer?
Most patients are diagnosed with early stage bladder cancer, or non-muscle invasive bladder cancer (NMIBC). Once the initial cancer is removed via transurethral resection of bladder tumor (TURBT), lifelong surveillance is needed to detect recurrence, which may occur at any time in a high rate of patients.
For high-risk NMIBC, monitoring using office cystoscopy is recommended every 3 months for the first 2 years after diagnosis. Noninvasive urine biomarkers aim to reduce this significant burden. One such biomarker, CxMonitor, has shown promise in early phase clinical studies, but additional trials are needed.
Another challenge is the difficulty of detecting all the cancer burden in the bladder following TURBT using the typical 'white light' source. Narrow band imaging and blue light cystoscopy aim to address this. Though the data are mixed, these technologies appear to improve detection rates and possibly the completeness of TURBT. However, a randomized trial comparing blue-light-guided and standard white-light-guided TURBT showed no difference in recurrence rates.
How do you determine the staging of bladder cancer?
Bladder cancer staging is based on the pathology report from TURBT plus axial imaging of the chest, abdomen, and pelvis to evaluate for metastatic disease. FDG PET scan may help assess for distant metastasis, and CT urogram often helps evaluate for upper tract urothelial tumors.
For localized NMIBC, we typically assess the need for adjuvant therapy following TURBT to reduce the risk for recurrence or progression. Standard-of-care treatment for high-risk NMIBC is bacillus Calmette-Guérin (BCG). Because of the BCG shortage worldwide and lack of responsiveness to BCG in some patients, additional treatments have been explored, with sequential chemotherapy — specifically gemcitabine + docetaxel (gem/doce) — gaining the most traction.
We have no reliable tools to predict which patients are less likely to respond to BCG or gem/doce. Computational histologic artificial intelligence has been used to develop assays to help predict response to BCG, preserve BCG for patients most likely to respond, and route others to different treatments. More investigation is needed to see how these tests perform prospectively.
How do you manage patients with bladder cancer?
Surgery is often needed to remove the primary bladder tumor. Adjuvant intravesical therapies following a complete TURBT are recommended for intermediate- or high-risk patients with NMIBC to help prevent recurrence and progression. For patients with suspected low-risk NMIBC, a single dose of gemcitabine immediately after TURBT reduced the risk for recurrence from 47% to 35%.
Complications following TURBT are typically minor. In a prospective study of 159 patients undergoing TURBT, 10% had an unplanned emergency room visit, 79% experienced hematuria, and one third had bladder spasms and incontinence. Patient education and preoperative counseling may help reduce the burden of complications and postoperative readmission.
Can you tell us about recently approved bladder cancer therapies?
Perioperative durvalumab was studied in combination with gemcitabine and cisplatin (GC) for neoadjuvant therapy in patients with muscle invasive bladder cancer. This three-drug regimen was compared to the standard GC regimen in the NIAGARA trial. Overall survival at 2 years following cystectomy was improved by 8% in the durvalumab arm.
Nogapendekin alfa inbakicept was evaluated in patients with NMIBC unresponsive to BCG. This drug modulates the local immune microenvironment in the bladder as an IL-15 super-agonist and must be given with BCG. In the pivotal study, 71% of patients had an initial complete response with a median duration of 26 months.
Mitomycin intravesical solution has been investigated in patients with low-grade intermediate-risk NMIBC, who often must undergo frequent TURBTs that can negatively affect quality of life. This agent, given intravesically, delivers a slow release of chemotherapy that ablates the tumors. With this strategy, 80% of patients were tumor free without requiring surgery at 3 months, and 82% remained free of cancer 12 months later. It has similar efficacy to TURBT but involves six weekly instillations vs one trip to the operating room.
Can you tell us more about upcoming therapies and clinical trial results in the near future?
I will be excited to see the results from the BRIDGE trial (ECOG-ACRIN EA8212), which met its patient accrual in July 2025. This trial randomized over 700 newly diagnosed patients who were BCG naive with high-grade NMIBC to BCG vs gem/doce. The primary objective is to assess event-free survival. Patient-reported outcomes are also being collected.
TAR-200, which is under FDA review, involves a novel drug delivery system that is inserted in the bladder and slowly releases gemcitabine to treat early stages of bladder cancer. A July 2025 press release cited an 82% complete response rate against bladder cancer, with 52% remaining cancer free for at least 1 year.