Progress in invasive and advanced bladder cancer: shooting for the moon

Michael S. Cookson, MD, MMHC

May, which is Bladder Cancer Awareness Month, gives us the opportunity to focus on this aggressive, too-often lethal disease and review the progress made toward finding a cure. We are, of course, reminded of some grim statistics. According to the American Cancer Society, in 2023 there will be approximately 82,290 new cases of bladder cancer in the US (62,420 among men and 19,870 among women); in addition, about 16,710 individuals will die from the disease (12,160 men and 4550 in women).¹ Fortunately, the rates of deaths and new cases have both been declining during the past 10 years, as awareness and management have significantly advanced.

Advocacy has improved in large part due to the efforts of the Bladder Cancer Advocacy Network (BCAN), an organization made up of caregivers, survivors, advocates, and medical professionals and researchers. BCAN provides not only information but also fundraising and research support. Since its founding in 2005, it has accomplished tremendous things—educationally and financially.

Among the advances in disease management is the first-line recommendation of bladder preservation in invasive bladder cancer. Patients with this stage II disease, who were once relegated to palliative care, now have tumor resection and concurrent chemotherapy “as a category 1 option.”²

At this year’s American Urological Association Annual Meeting, Sam S. Chang, MD, MBA, from Vanderbilt University in Nashville, Tennessee, moderated an excellent plenary discussion on bladder preservation in patients with muscle-invasive disease. Optimal patient selection was emphasized. The ideal candidate for resection/chemotherapy would be one with a solitary T2/T3a tumor (< 5 cm) that is amenable to complete endoscopic resection, no carcinoma in situ, no hydronephrosis, and good bladder capacity. The outcome in such a patient appears to be equal to that achieved with radical cystectomy, although debate continues regarding what constitutes the optimal chemoradiotherapy regimen.

Clearly, a trend is emerging toward bladder-sparing in patients with invasive bladder cancer. This is particularly good news for an aging population and a disease that disproportionately affects elderly patients, whose median age at diagnosis is 73.

In addition, those who undergo radical cystectomy may benefit from a minimally invasive approach like robot-assisted laparoscopic cystectomy. Studies, including the RAZOR trial (NCT01157676), have demonstrated the equivalence of laparoscopic and open radical cystectomy, with a potential for shorter length of hospital stay and reduced need for transfusion.³ When combined with intracorporeal urinary diversion, a reduction in wound-related complications may further benefit select patients with invasive disease. These advances have led to better outcomes and reduced morbidity after radical cystectomy.

Another important development in advanced/metastatic bladder cancer management is treatment with immune checkpoint inhibitors (ICIs). ICIs are now standard therapy in advanced urothelial carcinoma and approved for maintenance after initial response to or stable disease after first-line platinum-based chemotherapy, as first-line therapy in platinum-ineligible patients with a PD-L1 positive tumor, and for platinum-ineligible and refractory patients.4 Finally, genomic profiling and targeted therapies are becoming more common in bladder cancer management. Such antibody drug conjugates as enfortumab vedotin (Padcev) and targeted agents as erdafitinib (Balversa) have been shown to be efficacious and are changing the treatment landscape.^4,5

In conclusion, the significant advances made over the past decade have led to improvements in overall survival and quality of life for patients with invasive and advanced bladder cancer. And initiatives like the National Cancer Institute’s Cancer Moonshot give us reason to be optimistic. The program is designed to garner resources across the federal government to speed progress in research, detection, treatment—and prevention. We anticipate that in the next decade, breakthroughs in genetic profiling of tumors for precision therapies will further reduce suffering and death from bladder cancer.

References

1. Siegel RL, Miller KD, Waggle NS, Jemal A. Cancer statistics, 2023. CA: Cancer J Clin. 2023;73(1):17-48. doi:10.3322/caac.21763

2. NCCN. Bladder cancer, version 2.2023. Accessed May 7, 2023. https://bit.ly/44Cwk1u

3. Smith ND, Castle EP, Gonzalgo ML, et al. The RAZOR (randomized open vs robotic cystectomy) trial: study design and trial update. BJU Int. 2015;115(2):198-205. doi:10.1111/bju.12699

4. Powles T, Rosenberg JE, Sonpavde GP, et al. Enfortumab vedotin in previously treated advanced urothelial carcinoma. N Engl J Med. 2021;384(12):1125-1135. doi:10.1056/NEJMoa2035807

5. Loriot Y, Necchi A, Park SH, et al. Erdafitinib in locally advanced or metastatic urothelial carcinoma. N Engl J Med. 2019;381(4):338-348. doi:10.1056/NEJMoa1817323