The landscape for the management of muscle-invasive bladder cancer is rapidly changing based on novel chemotherapy agents, data from randomized controlled trials, and new diagnostic tests. The new muscle-invasive bladder cancer 2024 amendment includes several updates to the guidelines that were carefully integrated analyzing abstracts from May 2020 to November 2023. It is critically important to remember that the AUA Guidelines are evidence based and the AUA can only consider published data when it produces a guideline. Based on the most recent published literature, we present some of the modified guidelines.

Guideline 9: Patients who have not received cisplatin-based neoadjuvant chemotherapy and have pT3-4 and/or N+ disease at cystectomy should be offered adjuvant cisplatin-based chemotherapy or adjuvant immunotherapy. Patients who have received cisplatin-based chemotherapy and have pT2-4 and/or N+ at cystectomy should be offered adjuvant immunotherapy. (Moderate Recommendation; Evidence Level: Grade C.) Several studies have been published showing the utility in adjuvant chemotherapy and immunotherapy in patients with high-risk bladder cancer. The CheckMate 274 trial utilized adjuvant nivolumab and showed significant improvement in disease-free survival and metastasis-free survival when compared with placebo (nearly double) in patients with high-risk disease features (ypT2-T4 and/or N+ disease or pT3-T4 and/or N+ disease in patients who did not receive neoadjuvant chemotherapy). This advantage was regardless of nodal status, programmed death-ligand 1 status, or the use of neoadjuvant chemotherapy.¹ In contrast, the IMvigor010 trial showed no significant improvement in disease-free survival of adjuvant atezolizumab in a similar high-risk bladder cancer population and it is currently not recommended.² The AMBASSADOR randomized controlled trial showed a statistically significant improvement in disease-free survival using adjuvant pembrolizumab compared with observation in high-risk muscle-invasive bladder cancer patients after radical cystectomy.³ Overall, these new studies offer additional data on implementing adjuvant therapies in high-risk bladder cancer patients and should be part of the multidisciplinary management of these patients.

Guideline 11: When performing a standard radical cystectomy with curative intent, clinicians should remove the bladder, prostate, and seminal vesicles in males; clinicians should remove the bladder in females and should consider removal of adjacent reproductive organs based on individual disease characteristics and the need to obtain negative margins. Organ-sparing procedures in females should be considered based on disease location and characteristics on an individual basis. (Clinical Principle.) The low overall incidence of urothelial cancer involving reproductive parts including the uterus, ovaries, and vagina and the absence of evidence suggesting any significant improved outcome by removing these organs should lead surgeons to preserve these organs when possible. There is good evidence that the preservation of these organs leads to improved sexual function and potentially improved hormonal function.⁴ The guidelines therefore recommend removal of these organs only on an individual basis. There is evolving evidence that the removal of the fallopian tubes can reduce the risk of ovarian cancer without affecting sexual or hormonal function, but further data are required to recommend this standardly. In contrast, around one-third of male patients undergoing radical cystectomy will have prostatic urethral involvement.⁵ Therefore, the guidelines continue to recommend removal of the prostate and seminal vesicles. Prostate-sparing procedures are not standardly recommended, nor have they been shown to be superior to nerve sparing when looking at postoperative erectile function. In conclusion, organ-sparing procedures should be evaluated and discussed on an individual basis, as long as they do not compromise complete tumor resection.

Guideline 20: When performing bilateral pelvic lymphadenectomy, clinicians should remove, at a minimum, the external and internal iliac and obturator lymph nodes (standard lymphadenectomy; Clinical Principle.) The data for performing extended lymph node dissection during radical cystectomy continue to evolve. There have now been 2 large randomized controlled trials completed examining extended vs standard lymph node dissection (NCT 01215071 and SWOG S1011).^6,7 Both of these trials have failed to demonstrate an advantage of extended over standard lymphadenectomy. In addition, there was an increased rate of complications and a higher perioperative mortality associated with extended lymph node dissection.^8,9 It should be pointed out that in the European trial there is a signal that there might be a small survival benefit of around 6%; however, this failed to meet the end point for the study and thus it was a negative study.⁷ Based on these studies, the guidelines do not recommend extended lymph node dissection. However, standard lymph node dissection remains the standard of care for patients undergoing radical cystectomy.

Guideline 25: For patients with muscle-invasive bladder cancer who have elected trimodality therapy with organ preservation, clinicians should offer maximal transurethral resection of bladder tumor followed by chemotherapy combined with external beam radiation therapy. Planned cystoscopic surveillance per high-risk nonmuscle-invasive bladder cancer schedule should be performed. (Strong Recommendation; Evidence Level: Grade B.) In select patients who desire bladder preservation or who are unfit for surgery, trimodal therapy remains the preferred treatment. In a retrospective, multi-institutional propensity score matched study, the authors compared N0M0 muscle-invasive bladder cancer patients who underwent trimodal therapy or cystectomy (patients qualified for both options), which showed that in well-selected patients (solitary tumors <7 cm, no or unilateral hydronephrosis, no multifocal carcinoma in situ), there are similar outcomes in metastasis-free survival, cancer-specific survival, disease-free survival, and overall survival.¹⁰ This study adds to the literature that in select patients seeking bladder preservation or who are not surgical candidates, trimodal therapy is the preferred treatment.

Finally, the Future Directions section is intended to identify topics for which there is currently insufficient evidence to recommend a particular approach or therapy. However, there may be ongoing trials or exploration that will be forthcoming and may influence practice as well as future guidelines. Some of these topics include the role of MRI (Vesical Imaging–Reporting and Data System), positron emission tomography scans, and circulating tumor cell DNA in staging, recurrence, and surveillance. Additionally, more research is needed to define the role of adjuvant therapy in patients who received neoadjuvant chemotherapy with high-risk muscle-invasive bladder cancer.