Comparison of the overall survival of different treatment methods in patients with Muscle-invasive bladder cancer: A retrospective study.

OBJECTIVES: Bladder-Sparing Approach was presented in patients who are not willing or not suitable for Radical Cystectomy (RC). There have been inconsistencies in the literature regarding the comparison of survival rates of these two methods. Our objective is to evaluate the survival rate of patients with muscle-invasive bladder cancer (MIBC) undergoing different treatment methods. DESIGN: Retrospective cross-sectional study. SETTING: A secondary care, multicenter study in Kerman, Iran 2008 to 2016. PARTICIPANTS: All 200 patients who were diagnosed with Muscle Invasive Bladder Cancer and were admitted to our hospitals. Patients with inaccessible medical files and patients with pathologies other than TCC were excluded. MAIN OUTCOME MEASURES: Radical cystectomy and different methods of bladder preservation were compared based on their survival rate. INTERVENTIONS: Radical cystectomy or bladder preservation. RESULTS: Overall survival of the patients was 2 years [95% CI: 1.37-2.63]. The overall 5-year survival rate of patients with MIBC was 32%. Having a 6.4 years overall survival, the RC group showed the highest survival compared with others (p = 0.01); the overall survival of patients undergoing TMT, TURT, chemotherapy, or radiotherapy monotherapy was 3.15 years [95% CI: 2.242-4.061], 4.06 [95% CI: 3.207-4.931], 2.58 [95% CI: 1.767-3.399], and 3.14 [95% CI: 1.614-4.672] years, respectively. Patients younger than 65 undergoing RC had an overall survival of 7 years, compared with 2 years for the TMT group. (p = 0.0001). CONCLUSIONS: The Bladder-Preservation method, as a replacement for RC, showed a lower overall survival rate in our study. A prospective randomized clinical trial may declare the best treatment.

Efficiency of bladder-sparing strategies for bladder cancer: an umbrella review.

Bladder preservation (BP) has emerged as a clinical alternative to radical cystectomy (RC) for alleviating the substantial physical and psychological burden imposed on localized bladder cancer patients. Nevertheless, disparities persist in the comparative evaluations of BP and RC. We aimed to address the disparities between BP and RC. An umbrella review and meta-analysis were conducted to explore these disparities. We extracted data from meta-analyses and randomized controlled trials (RCTs) selected after searching PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews. Review Manager 5.4.0 and R x64 4.1.3 were used to evaluate the collected data. Our study included 11 meta-analyses and 3 RCTs. In terms of progression-free survival, all the meta-analyses reported that patients with localized bladder cancer who underwent BP exhibited outcomes comparable to those who underwent RC. Meta-analyses regarding the outcomes of cancer-specific survival (CSS) and overall survival (OS) are controversial. To solve these issues, we conducted a pooled analysis of CSS data, which supported the similarity of CSS between BP and RC with no significant heterogeneity [odds ratio (OR): 1.2; 95% confidence interval (CI): 0.71-2.02; I2 = 26%]. Similarly, the pooled OS results extracted from three RCTs indicated the comparability of OS between BP and RC with no significant heterogeneity (OR: 1.12; 95% CI: 0.41-3.07; I2 = 33%). A combination of umbrella review and meta-analysis results suggested that BP had survival rates comparable to those of RC. We suggest that BP may be a more eligible therapy than RC for patients with localized muscle-invasive bladder cancer. This conclusion warrants further validation through randomized controlled trials.

Experimental and New Approaches for Bladder Preservation in Intermediate and High-Risk Non-Muscle-Invasive Bladder Cancer (NMIBC).

About 75% of bladder cancers are detected as non-muscle invasive. High-risk patients have high progression risk. Although the standard is transurethral resection of bladder tumor plus full dose intravesical BCG for one to 3 years, due to the high risk of progression, radical cystectomy may be considered in specific cases. Although radical cystectomy is still the best approach for high-grade NMIBC from an oncological perspective, its high morbidity and impact on quality of life motivate studies of new strategies that may reduce the need for cystectomy. We carried out a mini-review whose objectives were: 1 - to identify bladder-sparing alternatives that are being studied as possible treatment for patients with intermediate and high-risk NMIBC; 2 - understand the evidence that exists regarding success rate, follow-up, and side effects of different strategies. Several studies have sought alternatives for bladder preservation, including immunotherapy, intravesical chemotherapy, chemo-hyperthermia, antibody-drug conjugates, viral genetic therapy, and others with promising results. The selection of an optimal therapy for high-risk NMIBC that can reduce the need for cystectomy, with low toxicity and high efficacy, is of paramount importance and remains an issue, however, several known medications are being tested as bladder-preserving alternatives in this scenario and have shown promise in studies.

Beyond surgery: bladder preservation and the role of systemic treatment in localised muscle-invasive bladder cancer.

Over the last two to three decades the non-surgical curative management of bladder cancer has significantly progressed. Increasing evidence supports the use of bladder preservation as an alternative to radical cystectomy (RC) for localised muscle-invasive bladder cancer (MIBC). Radiosensitisation with chemotherapy or hypoxia modification improves the efficacy of radiotherapy. Systemic treatments play an important role in the management of localised MIBC with the benefit of neoadjuvant chemotherapy prior to radical treatment well established. The use of immune checkpoint inhibitors (ICIs) in the radical treatment of bladder cancer, their safe combination with radical radiotherapy regimens and whether the addition of ICIs improve rates of cure are outstanding questions beginning to be answered by ongoing clinical trials. In this narrative review, we discuss the current evidence for bladder preservation and the role of systemic treatments for localised MIBC.

Effect of Clinical Complete Remission Following Neoadjuvant Pembrolizumab or Chemotherapy in Bladder-Preservation Strategy in Patients with Muscle-Invasive Bladder Cancer Declining Definitive Local Therapy.

This study aimed to evaluate the outcomes and identify the predictive factors of a bladder-preservation approach incorporating maximal transurethral resection of bladder tumor (TURBT) coupled with either pembrolizumab or chemotherapy for patients diagnosed with muscle-invasive bladder cancer (MIBC) who opted against definitive local therapy. We conducted a retrospective analysis on 53 MIBC (cT2-T3N0M0) patients who initially planned for neoadjuvant pembrolizumab or chemotherapy after maximal TURBT but later declined radical cystectomy and radiotherapy. Post-therapy clinical restaging and conservative bladder-preservation measures were employed. Clinical complete remission was defined as negative findings on cystoscopy with biopsy confirming the absence of malignancy if performed, negative urine cytology, and unremarkable cross-sectional imaging (either CT scan or MRI) following neoadjuvant therapy. Twenty-three patients received pembrolizumab, while thirty received chemotherapy. Our findings revealed that twenty-three (43.4%) patients achieved clinical complete response after neoadjuvant therapy. The complete remission rate was marginally higher in pembrolizumab group in comparison to chemotherapy group (52.1% vs. 36.7%, p = 0.26). After a median follow-up of 37.6 months, patients in the pembrolizumab group demonstrated a longer PFS (median, not reached vs. 20.2 months, p = 0.078) and OS (median, not reached vs. 26.8 months, p = 0.027) relative to those in chemotherapy group. Those achieving clinical complete remission post-neoadjuvant therapy also exhibited prolonged PFS (median, not reached vs. 10.2 months, p < 0.001) and OS (median, not reached vs. 24.4 months, p = 0.004). In the multivariate analysis, clinical complete remission subsequent to neoadjuvant therapy was independently associated with superior PFS and OS. In conclusion, bladder preservation emerges as a viable therapeutic strategy for a carefully selected cohort of MIBC patients without definitive local therapy, especially those achieving clinical complete remission following neoadjuvant treatment. For patients unfit for chemotherapy, pembrolizumab offers a promising alternative treatment option.

Downstaging guided neoadjuvant strategy shift and bladder preservation in locally advanced bladder cancer: A case report.

Background: The study of bladder preservation for muscle-invasive bladder cancer (MIBC) mainly focuses on the T2 stage, which remains difficult in the T3 and T4 stage. Pembrolizumab has been applied as neoadjuvant therapy followed by radical cystectomy for MIBC, gaining encouraging results in the phase II study. Disitamab vedotin, an antibody-drug conjugate (ADC), also achieved promising efficacy for refractory bladder cancer. However, the neoadjuvant therapy strategy of these drugs for bladder sparing remains further exploration. Case presentation: A patient with locally advanced MIBC at our institute underwent a neoadjuvant therapeutic regimen followed by transurethral resection of bladder tumor (TURBT) and concurrent chemoradiotherapy. In light of limited initial efficacy, we enacted an adaptive shift in the neoadjuvant treatment strategy, transitioning from a combination of gemcitabine, cis-platinum, and pembrolizumab to disitamab vedotin with pembrolizumab. This approach ultimately achieved bladder preservation, complete response, and a remarkable 1-year disease-free survival (DFS). Conclusion: Proactive evaluation in the early stages of tumor downstaging can serve as a guiding principle for neoadjuvant strategies. This is the first successful case of neoadjuvant pembrolizumab combined with disitamab vedotin and chemotherapy in MIBC patients achieving complete response and bladder preservation.

Comparative survival analysis of bladder preservation therapy versus radical cystectomy in muscle-invasive bladder cancer.

BACKGROUND: Bladder preservation therapy is an alternative to radical cystectomy in patients with muscle-invasive bladder cancer (MIBC). The purpose of this study is to compare survival outcomes between bladder preservation therapy and radical cystectomy in MIBC patients using an Asian nationwide cancer registry database. METHODS: From the Taiwan Cancer Registry database and the Taiwan National Health Insurance Research Database, we identified bladder cancer patients from 2008 to 2018. The patients with urothelial carcinoma and clinical stage T2-T4aN0-1 M0 were included. Propensity score matching by age, gender, clinical stage, cT classification, and Charlson Comorbidity Index score was used between those receiving bladder preservation therapy or radical cystectomy. Overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) were compared using the Kaplan-Meier method. Multivariate Cox regression models were used to determine the predictive factors of OS, CSS, and DFS. RESULTS: Following the propensity score matching, 393 MIBC patients were analyzed, 131 (33.3%) receiving bladder preservation therapy and 262 (66.7%) receiving radical cystectomy. After 5 years of the follow-up period the overall duration was with a median of 15.6 months. The treatment groups did not differ significantly in OS, CSS, and DFS (p = 0.2681, 0.7208, and 0.3616, respectively). In multivariable Cox regression models, bladder preservation therapy remained non-inferior to radical cystectomy in OS (adjusted hazard ratio [aHR] 1.08; 95% confidence interval [CI], 0.77-1.50; p = 0.6689), CSS (aHR, 1.06; 95% CI, 0.72-1.57; p = 0.7728), and DFS (aHR, 0.76; 95% CI, 0.46-1.27; p = 0.2929). Additionally, among patients ≥80 years, the use of bladder preservation therapy compared with radical cystectomy resulted in an equivalent OS, CSS and DSS. CONCLUSION: In Asian populations, bladder preservation therapy yielded similar survival outcomes as radical cystectomy in MIBC patients. Based on the results, it is evident that a multidisciplinary approach and shared decision-making are recommended for bladder cancer treatment.

Does Chemo-Radiotherapy Improve Survival Outcomes vs. Radiotherapy Alone for High-Grade cT1 Urothelial Carcinoma of the Bladder?

BACKGROUND: Non-muscle invasive bladder cancer (non-MIBC) that is high-grade and confined to the lamina propria (HGT1) often has an aggressive clinical course. Currently, there is limited data on the comparative effectiveness of RT vs. CRT for HGT1 non-MIBC. We hypothesized that CRT would be associated with improved overall survival (OS) vs. RT in HGT1 bladder cancer. METHODS: Patients diagnosed with HGT1 non-MIBC, and treated with transurethral resection of bladder tumor followed by either treatment with RT alone or CRT, were identified in the National Cancer Database. Inverse probability of treatment weighting (IPTW) was employed and weight-adjusted multivariable analysis (MVA) using Cox regression modeling was used to compare overall survival (OS) hazard ratios. OS was the primary endpoint, and was estimated using the Kaplan-Meier method and log-rank tests. RESULTS: A total of 259 patients with HGT1 UC were treated with: (i) RT alone (n = 123) or (ii) CRT (n = 136). Propensity-weighted MVA showed that combined modality treatment with CRT was associated with improved OS relative to radiation alone (Hazard Ratio [HR]: 0.62, 95% Confidence Interval (95% CI): 0.44-0.88, P = .007). Four-year OS for the CRT vs. RT alone was 36% and 19%, respectively (log-rank P <.008). CONCLUSION: For patients with HGT1 bladder cancer, concurrent CRT was associated with improved OS compared with radiation alone in a retrospective cohort. These results are hypothesis-generating. The NRG is currently developing a phase II randomized clinical trial comparing CRT to other novel, bladder preservation strategies.

Induction therapy with ipilimumab and nivolumab followed by consolidative chemoradiation as organ-sparing treatment in urothelial bladder cancer: study protocol of the INDIBLADE trial.

Introduction: Studies that assessed the efficacy of pre-operative immune checkpoint blockade (ICB) in locally advanced urothelial cancer of the bladder showed encouraging pathological complete response rates, suggesting that a bladder-sparing approach may be a viable option in a subset of patients. Chemoradiation is an alternative for radical cystectomy with similar oncological outcomes, but is still mainly used in selected patients with organ-confined tumors or patients ineligible to undergo radical cystectomy. We propose to sequentially administer ICB and chemoradiation to patients with (locally advanced) muscle-invasive bladder cancer. Methods: The INDIBLADE trial is an investigator-initiated, single-arm, multicenter phase 2 trial. Fifty patients with cT2-4aN0-2M0 urothelial bladder cancer will be treated with ipilimumab 3 mg/kg on day 1, ipilimumab 3 mg/kg plus nivolumab 1 mg/kg on day 22, and nivolumab 3 mg/kg on day 43 followed by chemoradiation. The primary endpoint is the bladder-intact event-free survival (BI-EFS). Events include: local or distant recurrence, salvage cystectomy, death and switch to platinum-based chemotherapy. We will also evaluate the potential of multiparametric magnetic resonance imaging of the bladder to identify non-responders, and we will assess the clearance of circulating tumor DNA as a biomarker for ICB treatment response. Discussion: This is the first trial in which the efficacy of induction combination ICB followed by chemoradiation is being evaluated to provide bladder-preservation in patients with (locally advanced) urothelial bladder cancer. Clinical Trial Registration: The INDIBLADE trial was registered on clinicaltrials.gov on January 21, 2022 (NCT05200988).

[Bladder preservation treatments for bladder cancer: Trimodality therapy, an overview of clinical practices in 2023]. / Traitements de préservation vésicale pour le cancer de vessie : la thérapie trimodale, aperçu des pratiques cliniques en 2023.

Bladder cancer is the most frequent tumor of the urinary tract. Patients diagnosed at a stage when the tumor has spread into or through the muscle layer of the bladder wall are usually treated with cystectomy. The evolution of cancer treatments, related to the development of alternative treatment options to the historical surgical standard and to the implication of the patient as an actor in decision-making, trends towards organ and function preservation without sacrificing efficacy. Trimodality therapy, which is a maximal transurethral resection of the tumor followed by concurrent chemoradiation, is an interesting therapeutic alternative for patients unfit for surgery and for those wishing to benefit from organ preservation. Radiotherapy offers excellent treatment possibilities for muscle-invasive bladder cancer. In selected T2-stage patients fit for trimodality therapy, it has an equivalent oncological outcome compared to cystectomy while having less severe complications and offering organ preservation. It remains feasible in inoperable patients while offering significant perspectives of relapse-free survival. Finally, it also is an efficient palliative treatment in patients where mid-term local control and hemostasis are sought after.

Management of surgically inoperable muscle-invasive bladder cancer in a resource constraint setting at a tertiary care center by bladder preservation protocol: Case series.

Introduction: Urinary bladder cancer is a major cause of morbidity and mortality worldwide. As per the data from the US cancer registry, it was diagnosed in nearly 71,000 patients and led to 14000 deaths in 2013. The Indian data in this regard are lacking with few case reports and epidemiological data only. The paucity of treatment data in this regard led us to undertake this prospective study at our radiation oncology canter. Carcinoma urinary bladder is a heterogeneous disease with variable natural history. Male preponderance and association with cigarette smoking appears to be the foremost in natural history of the disease. Our data analyzed the management of muscle-invasive medically and surgically inoperable carcinoma urinary bladder in a resource constraint setting at a tertiary care center by bladder preservation protocol (BPP). Materials and Methods: This prospective study was aimed to evaluate the treatment outcome in surgically inoperable muscle-invasive carcinoma urinary bladder in a resource constraint setting at a tertiary care center by BPP. All patients were treated with telecobalt 60 machine up to a dose of 60-66 Gy along with concurrent chemotherapy. Interim assessment was done at 40 Gy. Results: A total of nine patients were taken up for treatment with BPP. All patients were evaluated with standard evaluation protocol. All patients were followed up till any event occurred and till 6 years. Out of nine patients treated, six patients are still alive without any progression of disease and are disease free with standard evaluation on follow-up. Two patients died during the 1st year of follow-up. One patient progressed with lung and abdominal metastases 5 months after the completion of treatment and one patient was lost to follow-up. Conclusion: BPP using trimodality therapy is a suitable alternative to radical cystectomy in medically and surgically inoperable carcinoma urinary bladder. These patients should be highly compliant for regular follow-up, and acute and long-term toxicity should be evaluated in detail at each visit. BPP gives a ray of hope in such settings and should be done with caution. In our study, we treated all these patients in our resource constraint settings with good results and high survival rates. Our integrated team of radiation oncologists, medical oncologists, and urologists closely followed up these patients in order to optimize outcomes.

Bladder-sparing approaches for muscle invasive bladder cancer: a narrative review of current evidence and future perspectives.

Background and Objective: In recent years, the application of less-invasive "bladder-sparing" trimodal therapy (TMT) in selected muscle-invasive bladder cancer (MIBC) patients unfit for or who declined radical cystectomy (RC) has been increasing. This review aims to summarize the current evidence and future perspectives of bladder-sparing therapy for MIBC. Methods: A non-systematic Medline/PubMed literature search was conducted on July 2022 with the following keywords 'MIBC', 'bladder-sparing', 'chemotherapy', 'radiotherapy', 'trimodal', 'multimodal', and 'immunotherapy'. Key Content and Findings: All monotherapies are inferior to RC or combination therapy and should not be routinely used for curative intent. Radiotherapy (RT) alone has been shown to have poorer outcomes when compared to chemoradiotherapy. The ideal selection criteria for TMT include good bladder function and capacity, clinical stage within cT2, complete transurethral resection of bladder tumor (TURBT), no prior history of pelvic RT, no extensive carcinoma in situ (CIS), and absence of hydronephrosis. The emergence of immunotherapy may further increase the effect of bladder-sparing therapy. Novel predictive biomarkers are awaited for more precise patient selection and better oncological outcomes. Conclusions: TMT is a well-tolerated and offers a curative alternative approach to RC for selected patients with localized MIBC. Appropriate patient selection and a multi-disciplinary approach is crucial in achieving good oncologic control with bladder-sparing therapy.

Bladder preservation by neoadjuvant chemotherapy followed by concurrent chemoradiation for muscle-invasive bladder cancer.

Introduction: In Egypt, bladder cancer (BC) represents about 8.7% of cancers in both sexes. In Egyptian men, it accounts for over 30% of all cancers, which makes it the second most frequent cancer. The standard curative treatment for patients with muscle-invasive bladder cancer (MIBC) has been radical cystectomy (RC) with urinary diversion and pelvic lymphadenectomy. Concomitant chemoradiation therapy (CCRT) in MIBC appears to produce results that are comparable to those of RC. Material and methods: Between January 2018 and March 2021, 34 BC- diagnosed patients, who refused RC, were enrolled. They received transurethral resection of the bladder tumour (TURBT) followed by 3 cycles of neoadjuvant chemotherapy (NACT) with gemcitabine, cisplatin, and CCRT. Concomitant chemoradiation therapy with cisplatin, as a chemosensitizer, was administered to patients who experienced a complete response (CR) and a partial response (PR) ≥ 50%. Results: Following NACT, CCRT was given to 27 patients (79.45%) who had either a PR > 50% or CR. Seven patients (20.5%) showed PR below 50%, stable disease, or progressive disease; 4 of them underwent RC followed by postoperative radiation. The average follow-up period was 46 months (range: 6-52 months). Twenty-three patients (67.6%) were still alive at the last check-up. Disease-free survival and 3-year overall survival were 70.8% and 65.1%, respectively. Conclusions: Bladder preservation provides survival rates comparable to those of MIBC patients, but with a higher quality of life. The findings show good survival rates without metastasis; nevertheless, more multicentre trials with larger sample sizes and longer follow-up periods are required to confirm these findings.

Proton beam therapy for muscle-invasive bladder cancer: A systematic review and analysis with Proton-Net, a multicenter prospective patient registry database.

To assess the safety and efficacy of proton beam therapy (PBT) for muscle-invasive bladder cancer (MIBC), we examined the outcomes of 36 patients with MIBC (cT2-4aN0M0) who were enrolled in the Proton-Net prospective registry study and received PBT with concurrent chemotherapy from May 2016 to June 2018. PBT was also compared with X-ray chemoradiotherapy in a systematic review (X-ray (photon) radiotherapy). The radiotherapy consisted of 40-41.4 Gy (relative biological effectiveness (RBE) delivered in 20-23 fractions to the pelvic cavity or the entire bladder using X-rays or proton beams, followed by a boost of 19.8-36.3 Gy (RBE) delivered in 10-14 fractions to all tumor sites in the bladder. Concurrently, radiotherapy was given with intra-arterial or systemic chemotherapy of cisplatin alone or in combination with methotrexate or gemcitabine. Overall survival (OS), progression-free survival (PFS) and local control (LC) rates were 90.8, 71.4 and 84.6%, respectively, after 3 years. Only one case (2.8%) experienced a treatment-related late adverse event of Grade 3 urinary tract obstruction, and no severe gastrointestinal adverse events occurred. According to the findings of the systematic review, the 3-year outcomes of XRT were 57-84.8% in OS, 39-78% in PFS and 51-68% in LC. The weighted mean frequency of adverse events of Grade 3 or higher in the gastrointestinal and genitourinary systems was 6.2 and 2.2%, respectively. More data from long-term follow-up will provide us with the appropriate use of PBT and validate its efficacy for MIBC.

For Which Patients Should Bladder Preservation Be Considered After a Complete Response to Neoadjuvant Chemotherapy.

Given the morbidity associated with radical cystectomy (RC) and the significant survival benefit for patients who experience tumor downstaging after neoadjuvant chemotherapy (NAC), there is growing interest in bladder preservation strategies for select patients who have a complete response (CR) to NAC. In this mini-review we discuss the concept of avoiding RC as an alternative option for patients who experience a clinical CR following NAC. Several studies support this concept, with comparable long-term survival outcomes observed for patients with cT0 disease after NAC and patients undergoing RC. However, the definitive approach and the optimal surveillance strategy for patients with a clinical CR who choose bladder preservation are lacking. A dynamic response-driven bladder preservation strategy is a highly anticipated option for patients and is needed to avoid debilitating overtreatment. PATIENT SUMMARY: For selected patients with bladder cancer who experience a complete response to chemotherapy before any surgery, close follow-up might be an alternative option to surgical removal of the bladder without compromising cancer control.

Sequential Treatment With Bacillus Calmette-Güerin (BCG) and Mitomycin C Administered With Electromotive Drug Administration (EMDA) in Patients With High-Risk Nonmuscle Invasive Bladder Cancer After BCG Failure.

BACKGROUND: Nowadays, there is no standard non-surgical treatment for patients with nonmuscle invasive bladder cancer (NMIBC) in whom Bacillus Calmette-Güerin (BCG) therapy has failed. OBJECTIVES: To assess the clinical and oncological outcomes of sequential treatment with Bacillus Calmette-Guerin (BCG) and Mitomycin C (MMC) administered with Electromotive Drug Administration (EMDA) in patients with high-risk NMIBC who fail BCG immunotherapy. MATERIAL AND METHODS: We retrospectively studied patients with NMIBC who failed BCG and received alternating BCG and Mitomycin C with EMDA between 2010 and 2020. Treatment schedule consisted in an induction therapy with 6 instillations (BCG, BCG, MMC + EMDA, BCG, BCG, MMC + EMDA) and a 1-year maintenance. Complete response (CR) was defined as the absence of high-grade (HG) recurrences during follow-up, and progression was defined as the occurrence of muscle invasive or metastatic disease. CR rate was estimated at 3, 6, 12, and 24 months. Progression rate and toxicity were also assessed. RESULTS: Twenty-two patients were included with a median age of 73 years. Fifty percent of tumors were single, 90% were smaller than 1.5cm, 40% were GII (HG) and 40% were Ta. CR rate was 95.5%, 81% and 70% at 3 and 6 months, 12 months and 24 months, respectively. With a median follow-up of 28.8 months, 6 patients (27%) presented HG recurrence and only 1 patient (4.5%) progressed and ended in cystectomy. This patient died due to metastatic disease. Treatment was well tolerated and 22% of the patients presented adverse effects, being dysuria the most frequent one. CONCLUSION: Sequential treatment with BCG and Mitomycin C with EMDA achieved good responses and low toxicity in selected patients who did not respond to BCG. Only 1 patient ended in cystectomy and died due to metastatic disease, therefore, cystectomy was avoided in most cases.

Approaches to Clinical Complete Response after Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer: Possibilities and Limitations.

In the surgical oncology field, the change from a past radical surgery to an organ preserving surgery is a big trend. In muscle-invasive bladder cancer treatment, neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is the standard of care for muscle-invasive bladder cancer (MIBC) patients eligible for cisplatin. There is a growing interest in bladder preserving strategies after NAC because good oncologic outcome has been reported for pathologic complete response (pCR) patients after NAC, and many studies have continued to discuss whether bladder preservation treatment is possible for these patients. However, in actual clinical practice, decision-making should be determined according to clinical staging and there is a gap that cannot be ignored between clinical complete response (cCR) and pCR. Currently, there is a lack in a uniform approach to post-NAC restaging of MIBC and a standardized cCR definition. In this review, we clarify the gap between cCR and pCR at the current situation and focus on emerging strategies in bladder preservation in selected patients with MIBC who achieve cCR following NAC.

Treatment trends of muscle invasive bladder cancer: Evidence from the Surveillance, Epidemiology, and End Results database, 1988 to 2013.

Objective: Guidelines for muscle-invasive bladder cancer (MIBC) recommend that patients receive neoadjuvant chemotherapy with radical cystectomy as treatment over radical cystectomy alone. Though trends and practice patterns of MIBC have been defined using the National Cancer Database, data using the Surveillance, Epidemiology, and End Results (SEER) program have been poorly described. Methods: Using the SEER database, we collected data of MIBC according to the American Joint Commission on Cancer. We considered differences in patient demographics and tumor characteristics based on three treatment groups: chemotherapy (both adjuvant and neoadjuvant) with radical cystectomy, radical cystectomy, and chemoradiotherapy. Multinomial logistic regression was performed to compare likelihood ratios. Temporal trends were included for each treatment group. Kaplan-Meier curves were performed to compare cause-specific survival. A Cox proportional-hazards model was utilized to describe predictors of survival. Results: Of 16 728 patients, 10 468 patients received radical cystectomy alone, 3236 received chemotherapy with radical cystectomy, and 3024 received chemoradiotherapy. Patients who received chemoradiotherapy over radical cystectomy were older and more likely to be African American; stage III patients tended to be divorced. Patients who received chemotherapy with radical cystectomy tended to be males; stage II patients were less likely to be Asian than Caucasian. Stage III patients were less likely to receive chemoradiotherapy as a treatment option than stage II. Chemotherapy with radical cystectomy and chemoradiotherapy are both underutilized treatment options, though increasingly utilized. Kaplan-Meier survival curves showed significant differences between stage II and III tumors at each interval. A Cox proportional-hazards model showed differences in gender, tumor stage, treatment modality, age, and marital status. Conclusion: Radical cystectomy alone is still the most commonly used treatment for muscle-invasive bladder cancer based on temporal trends. Significant disparities exist in those who receive radical cystectomy over chemoradiotherapy for treatment.

Bladder preservation or complete cystectomy during pelvic exenteration of patients with locally advanced or recurrent rectal cancer, what should we do?

INTRODUCTION: In patients with locally advanced (LARC) or locally recurrent (LRRC) rectal cancer and bladder involvement, pelvic exenteration (PE) with partial (PC) or radical (RC) cystectomy can potentially offer a cure. The study aim was to compare PC and RC in PE patients in terms of oncological outcome, post-operative complications and quality-of-life (QoL). MATERIALS & METHODS: This was a retrospective cohort analysis of a prospectively maintained surgical database. Patients who underwent PE for LARC or LRRC cancer with bladder involvement between 1998 and 2021 were included. Post-operative complications and overall survival were compared between patients with PC and RC. RESULTS: 60 PC patients and 269 RC patients were included. Overall R0 resection was 84.3%. Patients with LRRC and PC had poorest oncological outcome with 69% R0 resection; patients with LARC and PC demonstrated highest R0 rate of 96.3% (P = 0.008). Overall, 1-, 3- and 5-year OS was 90.8%, 68.1% and 58.6% after PC, and 88.7%, 62.2% and 49.5% after RC. Rates of urinary sepsis or urological leaks did not differ between groups, however, RC patients experienced significantly higher rates of perineal wound- and flap-related complications (39.8% vs 25.0%, P = 0.032). CONCLUSION: PC as part of PE can be performed safely with good oncological outcome in patients with LARC. In patients with LRRC, PC results in poor oncological outcome and a more aggressive surgical approach with RC seems justified. The main benefit of PC is a reduction in wound related complications compared to RC, although more urological re-interventions are observed in this group.

Assessment of Tolerability, Response and Complications of Concurrent Chemoradiation With Capecitabine and Cisplatin in Muscle-Invasive Bladder Cancer; A Single Arm Study.

PURPOSE: To evaluate the feasibility, tolerance and efficacy of cisplatin+capecitabine as a proposed combination in concurrent chemoradiotherapy for patients with muscle-invasive bladder cancer (MIBC). METHODS: MIBC patients with stage T2-T4aN0M0 participated in this single-arm clinical trial. After maximal TURBT, 66Gy/33 daily fractions of radiation were administered with concurrent chemotherapy of cisplatin (35 mg/m2) and capecitabine (625 mg/m2). The primary endpoint was treatment tolerability, defined as receiving capecitabine+cisplatin combination for at least 5 weeks during radiation therapy. The secondary endpoints included complete response (CR) and acute toxicity rates. RESULTS: This study included 19 MIBC patients from 2018 to 2019. Eighteen patients (94.7%, 95%CI: 75.4-99.0) completed the planned treatment course. Only one patient (5.26%, 95%CI: 0.9-24.6) discontinued the treatment due to grade-3 GI toxicity. Among those who completed the treatment, CR was seen in 12 patients (66.7%, 95% CI = 44.4-88.9) with no grade ≥ 3 toxicities. The most common grade-2 side effects during therapy were renal complications (57.9%), and the only grade-2 complication after therapy was urinary-related (11.1%). The median follow-up was 31 months and the median overall survival (OS) was 31 months. The 2-year OS was 78% (95% CI 58.4-97.6), Cystectomy-free survival was 61% (95% CI: 37.5-84.5), and the median OS after recurrence was 13 months. Distant metastases were the first type of recurrence in most patients with a recurrence, which occurred in 7 (36.8%) patients. Median metastasis-free survival (MFS) was 30 months, and 2-year MFS was 66% (95% CI:45-87). CONCLUSION: The promising tolerability rate seen with concurrent cisplatin+capecitabine in this study was comparable to the available literature. Thus, this combination concurrently with radiation warrants further studies in the context of chemoradiotherapy of MIBC.