Stesura Seveso Archivio Italiano di Urologia e Andrologia 2025; 97(2):13760 1 ORIGINAL PAPER INTRODUCTION Bladder cancer posed a significant epidemiological con- cern in the Arab world, as evidenced by the 2019 Global Burden of Disease Data. In Yemen, the age-standardized incidence rate (ASIR) was recorded at 4.374 per 100,000, amounting to a total of 535.947 cases. Gender-specific analysis revealed ASIRs of 7.003 for males and 4.584 for females, with corresponding age-standardized death rates (ASDR) of 1.863 for males and 1.433 for females. The Age-Standardized Disability-Adjusted Life Years (ASDALYs) attributed to bladder cancer in Yemen reached approxi- mately 7,400.041, resulting in 57.819 deaths and a mor- tality-incidence ratio (MIR) of 2.95 (1). In 2020, the inci- dence of bladder cancer among males was estimated at 4.0 per 100,000, with a mortality rate of 1.6 per 100,000, underscoring the public health challenge presented by this disease in the region (2). Muscle-invasive bladder cancer (MIBC) represents a signifi- cant global health challenge, necessitating complex, mul- tidisciplinary therapeutic approaches (3). Standard treat- ment protocols typically involve radical cystectomy with pelvic lymph node dissection, often integrated with neoadjuvant or adjuvant chemotherapy (AC) to improve oncological outcomes (3, 4). Indeed, radical cystectomy has been widely recognized as the gold standard treat- ment, demonstrating superior survival rates and reduced recurrence compared to less aggressive modalities (5, 6). Prognostic factors, including advanced age, non-urothe- lial variant histology, a reduced number of lymph nodes removed, lymph node status, tumor stage, and surgical margin status, are critical determinants of long-term sur- vival following radical cystectomy for MIBC (7, 8). Bladder cancer mortality remains a substantial concern, particularly in advanced disease stages, underscoring the imperative for effective interventions (9). However, the successful implementation of these guide- lines is contingent upon the availability of robust diag- nostic pathways and therapeutic infrastructure (6). In resource-constrained settings such as Yemen, the man- agement of MIBC presents considerable obstacles. These regions often face limitations in essential resources, including diagnostic imaging modalities, specialized sur- Background: The lack of a cohesive diagnos- tic and therapeutic framework for muscle- invasive bladder cancer (MIBC) in Yemen has resulted in sig- nificant variability in patient care. This study evaluates onco- logical outcomes and survival rates after radical cystectomy (RC) for MIBC patients in Yemen. Methods: We conducted a retrospective analysis of 300 MIBC patients who underwent RC between 2006 and 2020. Demographics, histopathological findings, and survival data were meticulously collected. Kaplan-Meier survival analysis estimated survival probabilities, while prognostic factors were evaluated using the log-rank test. Results: The median patient age was 67 years (IQR 65-70), with a male predominance (n = 184, 61.3%). Ileal loop recon- struction was the primary method of urinary diversion (n = 234, 78.0%). Urothelial carcinoma was the predominant diag- nosis (n = 246, 82.0%), followed by squamous cell carcinoma (n = 42, 14.0%). Postoperative complications occurred in 93 patients (31.0%), primarily Grade I (n = 61, 20.3%). Overall survival was 71.7% (n = 215), with 28.3% mortality due to non-cancer-related (n = 43, 14.3%) and bladder cancer-related causes (n = 35, 11.7%). The median overall survival was 191 months, with 1-year, 3-year, 5-year, and 10-year survival rates of 99%, 93%, 88%, and 82%, respectively. In the multivariate analysis, non-ileal conduit diversion (Hazard Ratio [HR] 5.21, 95% Confidence Interval [CI]: 1.80-15.00, p = 0.003), Stage IV disease (HR 2.76, 95% CI: 1.01-7.61, p = 0.050), lymph node positivity (HR 2.92, 95% CI: 1.15-7.42, p = 0.022), and squa- mous cell carcinoma (HR 3.09, 95% CI: 1.25-7.63, p = 0.022) were identified as predictors of mortality. Conclusions: This study highlights the urgent need for improved bladder cancer care in Yemen. Late-stage diagnosis and suboptimal surgical methods critically affect survival. Addressing these issues requires prioritizing early detection and standardized surgical techniques to develop effective care pathways for MIBC patients. KEY WORDS: Muscle-invasive bladder cancer; Cystectomy; Yemen; Disease-free survival; Mortality; Oncological outcomes. Submitted 20 February 2025; Accepted 24 February 2025 Current status of management and outcomes of muscle-invasive bladder cancer in Yemen: A retrospective observational study Khaled Al-Kohlany 1, Amal Al-Maleki 2, Majdi Al-Shami 3, Hani Hussein 4, Faisal Ahmed 5 1 Department of Urology, General Military Hospital, Sana'a, Yemen; 2 Department of Obstetrics and Gynecology, Palestine Hospital for Motherhood and Childhood, Sana'a, Yemen; 3 Department of Urology, General Military Hospital, Sana'a, Yemen; 4 Department of Urology, 22 MAY Typical Specialized Surgical Center, Sana'a, Yemen; 5 Department of Urology, School of Medicine, Ibb University, Ibb, Yemen. DOI: 10.4081/aiua.2025.13760 Summary Archivio Italiano di Urologia e Andrologia 2025; 97(2):13760 K. Al-Kohlany, A. Al-Maleki, M. Al-Shami, H. Hussein, F. Ahmed 2 gical equipment, and access to systemic therapies (10, 11). Moreover, limited access to trained urologic oncolo- gists and comprehensive supportive care services can adversely affect patient outcomes. The absence of stan- dardized protocols, compounded by these resource con- straints, can lead to heterogeneous patient management and potentially compromise treatment efficacy. Therefore, this study seeks to investigate the current sta- tus of MIBC management and the associated oncological outcomes and survival rates following radical cystectomy in Yemen, a resource-limited environment. We present a retrospective analysis of oncological outcomes and sur- vival following radical cystectomy for MIBC performed by a single surgeon at tertiary referral centers. By character- izing the experiences of patients undergoing surgical treatment for MIBC in Yemen, this study aims to identify areas for improvement in the diagnosis, treatment, and ultimately, survival of this vulnerable patient population. This study is crucial, as it not only provides insight into existing practices but also highlights gaps in the health- care system. These insights may be used to inform the development of evidence-based national guidelines and recommendations for bladder cancer treatment in Yemen. PATIENTS AND METHODS Study design This retrospective observational study analyzed data from approximately 300 patients diagnosed with MIBC who underwent radical cystectomy at various governmental and private healthcare facilities in Sana'a, Yemen, between January 2006 and March 2020. The study adhered to the principles outlined in the Declaration of Helsinki and received ethical approval from the Ethics Research Committees of the General Military Hospital in Sana'a. Given the retrospective nature of the study, the ethics committee waived the requirement for individual patient consent for chart review. All patient data were encrypted and anonymized to ensure confidentiality. Inclusion criteria Patients diagnosed with MIBC who underwent radical cystectomy were included in the study, irrespective of tumor behavior or histology, with the exception of those diagnosed with lymphomas or small cell carcinomas. All included patients were managed by a single urologist with over five years of experience in oncologic surgery (K. A-K.). Exclusion criteria Patients were excluded from this analysis for the follow- ing reasons: failure to undergo radical cystectomy; pres- ence of documented clinical metastatic disease or non- invasive disease; a history of multiple primary cancers; a follow-up duration of less than six months; or treatment conducted by a different urologic team. Treatment and follow-up Preoperative staging comprised abdominal and pelvic com- puted tomography (CT) scans, chest X-rays, and transurethral resection of bladder tumors (TURBT). Radical cystectomy (RC) was performed, which included either bilateral or limited pelvic lymph node dissection (PLND), with prostatectomy and seminal vesiculectomy conducted for male patients. Female patients also underwent hysterectomy, anterior vaginal wall resection, and bilateral salpingo-oophorectomy, as dictated by the presence of involvement in these organs. The execu- tion and extent of lymph node dissection, along with the choice of urinary diversion, were determined based on patient preferences and the recommendations of the department’s specialists. Post-cystectomy follow-up involved clinical examination, laboratory studies, chest radiography, and abdominal/pelvic CT scans, with follow-up appointments scheduled every two months during the first year, semi-annually during the second year, and annually thereafter. Treatment failure was defined as radiological evidence of tumor relapse, catego- rized as either local recurrence or distant metastasis. Neoadjuvant chemotherapy (NAC) was administered to selected patients with clinically localized urothelial tumors. AC was offered to patients with pathological stage T3 or greater and/or node-positive disease unless medically con- traindicated or declined by the patient; this regimen was initiated within three months of surgery. Data collection Comprehensive data were meticulously extracted from patient charts and compiled into a Microsoft Excel data- base. The collected data included demographic informa- tion (age, sex, smoking status) and key clinicopathologi- cal variables such as the date of diagnosis, tumor histol- ogy and behavior, date of last follow-up or date of death, and cause of death (whether bladder cancer-related or due to other causes). Tumors were classified pathologi- cally using the 2002 TNM system established by the International Union Against Cancer and graded according to the World Health Organization system from 2004 (12, 13). Additional noteworthy factors were documented, including the American Society of Anesthesiologists (ASA) classification, type of urinary diversion, and any postop- erative complications or mortality. Duplicate records and cases with implausible dates of diagnosis (e.g., incidence date after the date of death or less than two weeks from death for patients undergoing radiotherapy and/or chemotherapy) were excluded from analysis. Postoperative complications occurring within 30- and 90-days following surgery were classified according to the Clavien-Dindo grading system, categorized as overall (any grade), minor (grades 1-2), and major (grades 3-5) (14). Postoperative ileus was defined as the inability to tolerate oral alimentation after cystectomy or the occur- rence of nausea, emesis, and abdominal distension that necessitated gastrointestinal decompression or nutrition- al support at any point during the postoperative period. Furthermore, data concerning complications specifically attributable to radical cystectomy were also collected. Study outcomes The primary outcome of this study was the association of bladder cancer treatment with overall survival (OS) and cancer-specific survival (CSS). Progression-free survival (PFS) was also assessed, defined as the interval from the index date to either the date of progression or death from Archivio Italiano di Urologia e Andrologia 2025; 97(2):13760 3 Bladder cancer management in Yemen any cause, or the initiation of a new treatment regimen, with patients who were alive and did not experience pro- gression censored at their last visit date. Median PFS (mPFS) was estimated, along with 95% confidence inter- vals (CIs), measured in months using the Kaplan-Meier method. CSS was defined as the duration from RC to can- cer-related death, while OS was defined as the duration from RC to any cause of death. The secondary outcome involved the identification of factors associated with mor- tality among patients undergoing radical cystectomy. Statistical analysis Data were analyzed using SPSS Statistics version 24 (IBM Corp., Armonk, NY). Descriptive statistics summarized patient characteristics and tumor features, using mean ± standard deviation for continuous variables and frequency and percentage for categorical variables. The Chi-squared test compared categorical variables, while survival analy- ses were conducted using Kaplan-Meier methods and Cox proportional hazards models to assess recurrence-free sur- vival (RFS), disease-free survival (DFS), and overall survival (OS). The log-rank test was applied to compare survival distributions, with a p-value of less than 0.05 considered statistically significant. Survival time was calculated from the date of diagnosis to either the date of death or the last follow-up, with patients who were alive and without clin- ical evidence of disease at the last follow-up censored. The proportional hazards assumption was evaluated for each covariate in the Cox regression models, with covari- ates selected for the final regression model based on the likelihood ratio test. Included covariates were ECOG per- formance status, type of urinary diversion, tumor grade, pathological stage, lymph node status, histological type, gender, smoking status, gender, and age. RESULTS Baseline patient, operative details, and tumor characteristics The patient cohort consisted of 300 individuals, with a mean age of 67.6 ± 4.8 years and a median age of 67.0 years (IQR 65.0, 70.0). The majority of patients were male (n = 184, 61.3%), and a substantial proportion reported a history of tobacco use (n = 186, 62.0%). Curative radical cystectomy was the most common surgi- cal intervention, performed in 272 patients (90.7%), fol- lowed by palliative cystectomy in 22 (7.3%) and salvage cystectomy in 6 (2.0%). Ileal loop urinary diversion was the most frequently employed reconstruction technique, used in 234 patients (78.0%). Other reconstruction tech- niques included ileal W neobladder (53 patients, 17.7%), ureterosigmoidostomy (5 patients, 1.7%), cutaneous ureterostomy (3 patients, 1.0%), indwelling PCN (1 patient, 0.3%), and Studer pouch (4 patients, 1.3%). Urothelial carcinoma was the predominant pathological diagnosis, observed in 246 patients (82.0%). Squamous cell carcinoma, mixed carcinoma, and adenocarcinoma were also identified in 42 (14.0%), 7 (2.3%), and 5 (1.7%) patients, respectively. The majority of tumors were classi- fied as high grade (n = 270, 90.0%). Stage II disease was the most frequently observed pathological stage (n = 131, 43.7%). Stage III and Stage IV disease were observed in 42 (14.0%) and 33 (11.0%) patients, respectively. Lymph node involvement was documented in a significant pro- portion of the cohort (n = 98, 32.7%) (Table 1). Postoperative and survival outcomes Postoperative complications were documented in 93 patients (31.0%). Grade I complications were the most common (n = 61, 20.3%). Grade II complications occurred in 21 patients (7.0%), while Grade III to V (major compli- cations) were observed in 6 (2.0%) and 7 (2.3%) patients, respectively. The mean follow-up duration was 102.1 months (SD 52.0), with a range of 1.0 to 227.0 months and a median of 111 months (IQR: 62, 141). Table 1. Baseline patient, operative details, and tumor characteristics in muscle-invasive bladder cancer patients undergoing radical cystectomy. Characteristic N (%) Age (years), mean ± SD 67.6 ± 4.8 Gender Female 116 (38.7%) Male 184 (61.3%) Smoking status No 114 (38.0%) Yes 186 (62.0%) ECOG performance status 0 131 (43.7%) 1 110 (36.7%) 2 59 (19.7%) Operative type Radical cystectomy 272 (90.7%) Palliative cystectomy 22 (7.3%) Salvage cystectomy 6 (2.0%) Urinary diversion type Ileal loop 234 (78.0%) Ileal W neobladder 53 (17.7%) Ureterosigmoidostomy 5 (1.7%) Cutaneous ureterostomy 3 (1.0%) Indwelling PCN 1 (0.3%) Studer pouch 4 (1.3%) Pathology type Urothelial carcinoma 246 (82.0%) Squamous cell carcinoma 42 (14.0%) Mixed carcinoma 7 (2.3%) Adenocarcinoma 5 (1.7%) Tumor stage Tis 57 (19.0%) I 37 (12.3%) II 131 (43.7%) III 42 (14.0%) IV 33 (11.0%) Tumor grade High 270 (90.0%) Low 30 (10.0%) Lymph node status Negative 202 (67.3%) Positive 98 (32.7%) Archivio Italiano di Urologia e Andrologia 2025; 97(2):13760 K. Al-Kohlany, A. Al-Maleki, M. Al-Shami, H. Hussein, F. Ahmed 4 The overall survival rate was 215 (71.7%), with 85 (28.3%) cases resulting in death. Specifically, 7 (2.3%) cases were mortality-related deaths that occurred during postoperative hospital admission within 30 days of the operation. Significantly, a substantial fraction of the cohort experienced mortality attributed to non-cancer causes (n = 43, 14.3%) or blad- der cancer-related causes (n = 35, 11.7%). At the time of data analysis, among patients who were alive, 184 (61.3%) were alive free of disease, and 31 (10.3%) were alive with disease (Table 2). Survival analysis Single-arm survival analysis of 293 patients with bladder cancer demonstrated a medi- an overall survival (mOS) of 191 months (95% CI: 116-267 months) (Figure 1). Kaplan-Meier estimates indicated 1-year, 3-year, 5-year, and 10-year survival proba- bilities of 99% (95% CI: 97%-100%), 93% (95% CI: 90%-96%), 88% (95% CI: 84%- 92%), and 82% (95% CI: 78%-87%), respectively. Factors associated with mortality Univariate Cox regression analysis revealed that ECOG performance status (2 vs. 0: HR 5.29, p < 0.001; 1 vs. 0: HR 3.80, p < 0.001), non-ileal conduit urinary diversion (HR 4.21, p < 0.001), high-grade tumors (HR 9.50, p < 0.001), advanced stage (Stage II vs. Tis: HR 5.16, p < 0.001; Stage IV vs. Tis: HR 6.10, p < 0.001), lymph node positivity (HR 11.95, p < 0.001), and squamous cell carcinoma histology (HR 16.78, p < 0.001) were significantly associated with increased mortal- ity (Table 3). However, multivariate Cox regression analysis demon- strated that only non-ileal conduit urinary diversion (HR 5.21, p = 0.003), Stage II (HR 2.56, p = 0.047), Stage IV Figure 1. Kaplan-Meier estimates of overall survival for Yemeni patients who underwent radical cystectomy. Table 2. Oncological outcomes and postoperative complications in muscle-invasive bladder cancer patients undergoing radical cystectomy. Characteristic N (%) Follow-up duration (months) Mean ± SD 102.1 ± 52.0 Range 1.0 to 227.0 Median 111 (IQR: 62, 141) Outcome Alive without disease 184 (61.3%) Non-cancer mortality 43 (14.3%) Cancer mortality 35 (11.7%) Died early 7 (2.3%) Alive with disease 31 (10.3%) Progression-free survival (PFS) Median PFS, 95% CI (months) 155 (143-191) Any complication No 207 (69.0%) Yes 93 (31.0%) Complication grade Grade 1 61 (20.3%) Grade 2 21 (7.0%) Grade 3 6 (2.0%) Grade 4 7 (2.3%) Table 3. Univariate Cox regression analysis of factors associated with overall survival in muscle-invasive bladder cancer patients undergoing radical cystectomy. Variable Subgroup N (%) Hazard ratio (95% CI) P-value ECOG performance status 0 131 (43.7) Ref 1 110 (36.7) 3.80 (1.89-7.64) < 0.001 2 59 (19.7) 5.29 (2.58-10.85) < 0.001 Urinary diversion type Ileal conduit diversion 287 (95.7) Ref Non-ileal conduit diversion 13 (4.3) 4.21 (2.31-7.67) < 0.001 Tumor grade Low grade 270 (90.0) Ref High grade 30 (10.0) 9.50 (5.87-15.37) < 0.001 Pathological stage Tis 57 (19.0) Ref I 37 (12.3) 0.03 (0.00-0.27) 0.002 II 131 (43.7) 5.16 (2.24-11.90) < 0.001 III 42 (14.0) 2.28 (0.87-5.99) 0.095 IV 33 (11.0) 6.10 (2.64-14.13) < 0.001 Lymph node status Negative 202 (67.3) Ref Positive 98 (32.7) 11.95 (7.11-20.08) < 0.001 Histological type Urothelial carcinoma 246 (82.0) Ref Squamous cell carcinoma 42 (14.0) 16.78 (10.09-27.91) < 0.001 Other 12 (4.0) 4.00 (1.99-8.03) < 0.001 Gender Female 116 (38.7) Ref Male 184 (61.3) 0.95 (0.61-1.46) 0.800 Smoking status No 114 (38.0) Ref Yes 186 (62.0) 0.86 (0.55-1.33) 0.496 Age (year) Mean (SD) 67.6 (4.8) 0.97 (0.93-1.01) 0.159 ECOG = Eastern Cooperative Oncology Group; HR = Hazard Ratio; CI = Confidence Interval; SD = Standard Deviation. Ref = Reference. "Other" in Histological Type includes Adenocarcinoma and Mixed Carcinoma. Archivio Italiano di Urologia e Andrologia 2025; 97(2):13760 5 Bladder cancer management in Yemen (HR 2.76, p = 0.050), lymph node positivity (HR 2.92, p = 0.022), and squamous cell carcinoma histology (HR 3.09, p = 0.022) remained significantly associated with overall mortality. While ECOG performance status and high-grade tumors did not achieve statistical significance in the multivariate model, the aforementioned factors demonstrated a significant independent impact on patient mortality (Table 4) (Figure 2 A-F). DISCUSSION The study provides a comprehensive evaluation of the management and outcomes of MIBC in Yemen over a period of 16 years. The data collected from patients indicate a median overall survival of 191 months, with 1-year, 3-year, 5-year, and 10-year survival probabilities of 99%, 93%, 88%, and 82%, respectively. Additionally, the result identified non-ileal conduit diversion, advanced stages of disease, lymph node positivity, and squamous cell carcinoma histology as significant independent predictors of overall mortality in bladder cancer patients. In contrast to studies in Western countries, which have reported 5-year survival rates of 54.5%-68% in bladder can- cer patients who underwent radical cystectomy (15, 16), the current study achieved a 5-year survival rate of 88%. This suggests that appropriate patient selection and surgical interventions can lead to comparable outcomes in diverse healthcare set- tings, despite geographical and infrastructural chal- lenges. In general, findings indicate that RC demonstrates efficacy in controlling local recur- rence, evidenced by a five-year DFS rate of 74% (17). Conditional survival analysis revealed that a Figure 2. Kaplan-Meier analysis of overall survival probability in Yemeni patients undergoing radical cystectomy, stratified by: (A) ECOG performance status; (B) Urinary diversion type; (C) Tumor grade; (D) Histological type; (E) Pathological stage; (F) Lymph node status. Table 4. Multivariate Cox regression analysis of factors associated with overall mortality in muscle-invasive bladder cancer patients undergoing radical cystectomy. Variable Subgroup Hazard Ratio (95% CI) p-value ECOG Performance Status 0 Ref 1 1.95 (0.79-4.83) 0.148 2 1.75 (0.72-4.26) 0.217 Urinary Diversion Type Ileal conduit diversion Ref Non-ileal conduit diversion 5.21 (1.75-15.47) 0.003 Tumor Grade Low Grade Ref High Grade 0.60 (0.29-1.25) 0.175 Pathological Stage Tis Ref I 0.02 (0.00-0.23) 0.001 II 2.56 (1.01-6.48) 0.047 III 2.58 (0.95-7.00) 0.062 IV 2.76 (1.00-7.61) 0.050 Lymph Node Status Negative Ref Positive 2.92 (1.17-7.31) 0.022 Histological Type Urothelial Carcinoma Ref Squamous Cell Carcinoma 3.09 (1.18-8.10) 0.022 Other 0.09 (0.03-0.29) < 0.001 ECOG = Eastern Cooperative Oncology Group; HR = Hazard Ratio; CI = Confidence Interval; SD = Standard Deviation. Ref = Reference. Archivio Italiano di Urologia e Andrologia 2025; 97(2):13760 K. Al-Kohlany, A. Al-Maleki, M. Al-Shami, H. Hussein, F. Ahmed 6 longer survivorship after surgery leads to an increase in OS and CSM-free survival probability in patients with MIBC. For instance, patients who were alive at 1 year after RC had 70% and 74% 5-year conditional OS and CSM-free survival rates, respectively, whereas patients who survived 5 years after surgery had 85% and 92% 5- year conditional OS and CSM-free survival rates (18, 19). These findings underscore the importance of optimizing surgical management in MIBC to improve patient prog- nosis in diverse healthcare settings. Radical cystectomy remains the gold standard for MIBC treatment due to its association with improved survival outcomes (5). However, the results of this study suggest that appropri- ate surgical interventions can lead to comparable out- comes in diverse healthcare settings, despite geographical and infrastructural challenges. Our study conducted in Yemen elucidates the significant prevalence of squamous cell carcinoma (SCC), which can be attributed to the country's high rates of schistosomiasis. Among the cases analyzed, urothelial carcinoma emerged as the most prevalent pathology, accounting for 82.5% of all instances, thereby corroborating findings from global studies that consistently identify urothelial carcinoma as the predominant variant of bladder cancer (9). Nonetheless, the 13.5% prevalence of SCC within our cohort warrants attention, particularly in the context of research emerging from regions with endemic schistoso- miasis, a well-established risk factor for SCC. Notably, Al- Samawi et al. (10) reported that 17% of bladder cancer cases in Yemen were classified as SCC. Furthermore, the literature indicates that SCC of the bladder is associated with increased aggressiveness and inferior survival out- comes, including diminished progression-free and cancer- specific survival, when compared to the urothelial histo- logical subtype (20-22). Furthermore, metastatic SCC is observed to respond inadequately to systemic treatments and radiotherapy (22). Concordant with previous find- ings, the SCC histopathological subtype in our study was significantly associated with elevated overall mortality. These observations underscore the pressing imperative for the development of targeted screening and management strategies aimed at addressing the distinct risk factors endemic to regions affected by schistosomiasis. While our study demonstrates promising overall and DFS rates, the reported 31.2% post-operative complication rate, including 7 cases of 30-day post-operative mortali- ty, underscores the imperative for enhanced post-opera- tive care and monitoring. This complication rate is con- sistent with findings from other reports, such as a sys- tematic review by Novara et al., which reported a post-RC complication range of 20% to 30% (23). Similarly, Katsimperis et al. identified gastrointestinal (20%), infec- tions (17%), and ileus (14%) complications as the most frequent, with the majority classified as Clavien I-II (45%) (24). Zakaria et al. reported an overall complica- tion rate of 30.6%, encompassing both early and late events, with a 90-day (Clavien grade III-IV) complication rate of 20.9% (25). These elevated complication rates may stem from disparities in healthcare infrastructure, patient management protocols, and adherence to surgical guidelines. Addressing these issues through refined surgi- cal techniques, optimized pre-operative patient prepara- tion, and improved post-operative care has the potential to reduce the complication rate in Yemeni patients. While numerous studies have investigated the impact of orthotopic neobladder (ON) and ileal conduit (IC) diver- sions on health-related quality of life (HRQoL) in bladder cancer patients, the influence of orthotopic neobladder on cancer control remains less defined. A systematic review found no significant difference in quality of life between continent and incontinent urinary diversions. However, orthotopic neobladder may offer HRQoL advantages through the preservation of body image (26). In contrast, the impact of orthotopic neobladder on sur- vival outcomes has been less extensively studied. Yossepowitch et al. (27) reported improved cancer-specific and overall survival with orthotopic neobladder com- pared to ileal conduit, though this significance was not maintained after stratification by disease stage (confined vs. non-confined). In contrast to this finding, Su et al. observed superior 5-year survival rates with orthotopic neobladder across all and specific T stages (28). After employing propensity score matching to mitigate baseline differences, orthotopic neobladder was identified as a protective factor for overall survival; however, subgroup analysis revealed that this benefit was primarily observed in patients with pathological T2 stage disease (28). Consistent with previous research, non-ileal conduit diversion was associated with increased overall mortality in our study. Our findings underscore the significance of certain prog- nostic factors in bladder cancer patients. Specifically, advanced tumor stage, lymph node involvement, and squamous cell carcinoma histology emerged as independ- ent predictors of overall mortality. These factors likely contribute to a poorer prognosis through several mecha- nisms. Advanced stage disease often indicates a more extensive local invasion and a higher likelihood of distant metastasis, rendering curative treatment more challeng- ing. Moreover, lymph node positivity signifies regional spread of the malignancy, further decreasing the likeli- hood of successful local control and increasing the risk of systemic dissemination. Notably, squamous cell carcino- ma is a less common histological subtype of bladder can- cer that is frequently associated with more aggressive bio- logical behavior and a decreased responsiveness to stan- dard platinum-based chemotherapy regimens, contribut- ing to its association with increased mortality. These results align with prior reports (29-32); and fur- ther emphasize the critical role of accurate staging, com- prehensive pathological assessment, and individualized treatment strategies that consider the unique characteris- tics of each patient's disease. Implications for future care The substantial morbidity associated with MIBC, coupled with the challenges identified in this study, highlights the need for a comprehensive cancer management program in Yemen. Interdisciplinary collaboration among urolo- gists, medical oncologists, and primary care providers is essential to optimize treatment pathways and improve patient outcomes. Furthermore, enhanced public health education focusing on early detection and timely inter- vention may significantly improve survival rates. Archivio Italiano di Urologia e Andrologia 2025; 97(2):13760 7 Bladder cancer management in Yemen Study limitations This study is subject to several limitations. The single- surgeon design potentially restricts the generalizability of the findings. The retrospective methodology introduces inherent selection bias and the potential for data incon- sistencies. The relatively small sample size limits statisti- cal power and the feasibility of conducting robust sub- group analyses. Variability in follow-up duration may impact the assessment of long-term outcomes. The absence of standardized treatment protocols could con- tribute to variability in post-operative results, while reliance on clinical documentation for complication reporting may lead to underreporting. Finally, the lack of comparative data from other institutions and the absence of several factors that may affect survival, such as chemotherapy, limits the contextualization of these find- ings within the broader landscape of bladder cancer man- agement. Future multi-center, randomized controlled tri- als incorporating diverse treatment protocols are recom- mended to address these limitations and further refine our understanding of MIBC management in this context. CONCLUSIONS This study highlights the urgent need for improved blad- der cancer care in Yemen. Late-stage diagnosis and sub- optimal surgical methods critically affect survival. Addressing these issues requires prioritizing early detec- tion and standardized surgical techniques to develop effective care pathways for MIBC patients. REFERENCES 1. Al Saidi I, Mohamedabugroon A, Sawalha A, Sultan I. Epidemiology of Bladder Cancer in the Arab World: 2019 Global Burden of Disease Data. Asian Pac J Cancer Prev. 2022; 23:2907-19. 2. 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Correspondence Khaled Al-Kohlany kalkohlani@gmail.com Majdi Al-Shami Majedialshami@gmail.com Department of Urology, General Military Hospital, Sana'a, Yemen Amal Al-Maleki majdi.alshami@yahoo.com Department of Obstetrics and Gynecology, Palestine Hospital for Motherhood and Childhood, Sana'a, Yemen Hani Hussein drhani01@gmail.com Department of Urology, 22 MAY Typical Specialized Surgical Center, Sana'a, Yemen Faisal Ahmed (Corresponding Author) fmaaa2006@yahoo.com Department of Urology, School of Medicine, Ibb University, Ibb, Yemen