Editing Muscle-Invasive Bladder Cancer (section)

=== Bladder Preservation/Multimodal Therapy ===

* A multi-disciplinary team discussion is preferred for patients considering bladder preservation.
*'''Successful bladder preservation should be viewed as a multimodal therapy involving:'''
*# '''Aggressive TUR'''
*# '''Systemic chemotherapy'''
*# '''Radiation therapy'''
** Historical series have demonstrated inferior results with single modality therapy (radical TUR, chemotherapy alone, or radiation alone) compared to that of radical cystectomy.

====Patient selection====
*'''<span style="color:#ff0000">Indications[https://pubmed.ncbi.nlm.nih.gov/28456635/ ★]</span>'''
*#'''<span style="color:#ff0000">Patients with newly diagnosed non-metastatic MIBC who desire to retain their bladder</span>'''
*#'''<span style="color:#ff0000">Patients with significant comorbidities for whom radical cystectomy is not a treatment option, clinicians should offer bladder</span>''' 
*#*'''Overall, bladder preserving therapy has been associated with decreased survival compared to RC'''
*#**'''Patients who are deemed “medically fit” to undergo cystectomy should be offered cystectomy as the standard of care'''
*#*Studies that support bladder preserving strategies, as a general rule, have highly select patient populations
*#*Bladder preservation should be undertaken with the goal of curative therapy and to maintain a functionally intact bladder
*'''<span style="color:#ff0000">Ideal characteristics for bladder preservation (4):[https://pubmed.ncbi.nlm.nih.gov/28456635/ ★]</span>'''
*# '''<span style="color:#ff0000">Unifocal tumor</span>'''
*#'''<span style="color:#ff0000">No CIS</span>'''
*#'''<span style="color:#ff0000">No evidence of hydronephrosis</span>'''
*# '''<span style="color:#ff0000">A tumor that can be completely transurethrally resected</span>'''
*'''Contraindications'''
**'''Relative'''
**#'''Large tumors unable to be resected by TURBT'''
**#'''Multifocal CIS'''
**#'''T3/T4 tumors,'''
**#'''Presence of hydronephrosis'''
**#Non-urothelial carcinoma
**##Patients with adenocarcinomas, sarcomas, and squamous cell carcinomas have not been included in prospective studies of radiation-based bladder preservation
**'''Unknown how variant histology affects outcomes associated with multi-modal bladder preserving therapy'''
*'''In patients under consideration for bladder preserving therapy, maximal debulking transurethral resection of bladder tumor and assessment of multifocal disease/carcinoma in situ should be performed'''
**In multiple prospective trials, the ability to resect all tumor predicted the best response to bladder preserving therapies.
**'''Random biopsies may help ensure that there is no associated CIS.'''

==== Multi-modal/Trimodal bladder preserving therapy ====
*Most of the literature supporting multi-modal bladder preserving therapy with radical cystectomy is from one RCT and several observational studies that have compared EBRT with and without chemotherapy vs. radical cystectomy[https://pubmed.ncbi.nlm.nih.gov/38661067/]
*'''<span style="color:#ff0000">Includes (3):</span>'''
*#'''<span style="color:#ff0000">Maximal transurethral resection of bladder tumor</span>'''
*# '''<span style="color:#ff0000">Chemotherapy combined with external beam radiation therapy</span>'''
*#'''<span style="color:#ff0000">Ongoing cystoscopy to evaluate response'''
*'''Radiation sensitizing chemotherapy'''
**Should be included when using multi-modal therapy with curative intent.
***Radiation with concurrent chemotherapy is superior to radiation alone.
**Several radiosensitizing chemotherapeutic agents have been shown safe and effective for trimodal bladder cancer therapy
***'''Various regimens of neoadjuvant, concurrent and adjuvant cisplatin-based regimens (e.g., cisplatin alone, CMV, cisplatin + paclitaxel or cisplatin + gemcitabine) have been studied.'''
***Alternatives for cisplatin-ineligible patients include gemcitabine or 5-fluorouracil and mitomycin C.
***Carboplatin should not be used as a radiosensitizer unless there are contraindications to cisplatin, 5-FU, and gemcitabine.
****Carboplatin has been found to be inferior to cisplatin in multimodal bladder preserving therapy
*'''<span style="color:#ff0000">Patient selection</span>'''
** '''<span style="color:#ff0000">AUA (4):</span>'''
**# '''<span style="color:#ff0000">Unifocal</span>'''
**# '''<span style="color:#ff0000">No CIS</span>'''
**# '''<span style="color:#ff0000">No evidence of hydronephrosis</span>'''
**# '''<span style="color:#ff0000">A tumor that can be completely transurethrally resected</span>'''
**'''<span style="color:#ff0000">CUA (6):</span>'''
**# '''<span style="color:#ff0000">Unifocal</span>'''
**# '''<span style="color:#ff0000">No CIS</span>'''
**# '''<span style="color:#ff0000">No hydronephrosis</span>'''
**# '''<span style="color:#ff0000">Small (<5cm) tumour</span>'''
**#'''<span style="color:#ff0000">Good bladder function</span>'''
**# '''<span style="color:#ff0000">Patient motivated for bladder preservation</span>'''
* '''Patients with obvious T3 disease on imaging, multifocal tumors, and/or incomplete macroscopic tumor resection are also suboptimal candidates for bladder preservation'''
* '''Strategies for trimodal bladder preservation (2): split- vs. continuous-course therapy'''
** '''Split-course'''
*** '''Based on the premise of midtreatment restaging'''
**** '''Patients are administered induction chemoradiation therapy to ≈40 Gy, which is followed by restaging with cross-sectional imaging and endoscopic evaluation.'''
**** '''If persistent invasive disease [even if lower stage] is noted, RC is recommended'''. '''Those without persistent invasive disease undergo consolidative chemoradiotherapy to ≈64 Gy.'''
** '''Continuous-course'''
*** '''Involves a full course of chemoradiation therapy followed by an endoscopic restaging examination 6 months after therapy''' '''to allow time for an adequate response to therapy.'''
** '''Regardless of approach, maximal tumor debulking before trimodal therapy is critical to optimize therapeutic results'''
*'''Follow-up'''
**'''For medically operable patients receiving staged multi-modal therapy, clinicians should offer a mid-course evaluation to allow for the early selection of non-responders before consolidation radiotherapy is given'''
**'''Following completion of bladder preserving therapy, patients should have a follow up cystoscopy with biopsy to identify occult persistent malignancy, and undergo regular surveillance with CT scans, cystoscopy, and urine cytology'''
***Those who are biopsy-proven complete responders to bladder preserving protocols remain at risk for both invasive and non-invasive recurrences as well as new tumors in the upper tracts.
***No direct evidence to determine optimal frequency of surveillance, published protocols recommend:
****Cystoscopy per high-risk NMIBC schedule
****Cross-sectional imaging of the abdomen and pelvis and chest imaging every 6 months for the first 2 years
**Unclear what proportion of patients who, having initially chosen bladder preservation, ultimately require cystectomy in a non-study setting.[https://pubmed.ncbi.nlm.nih.gov/38661067/]