Pathological and clinical outcomes of adrenalectomy: A multi-center experience in Saudi Arabia.

Objective: To determine the nature of adrenal pathology in patients undergoing adrenalectomy in Saudi Arabia over the last decade and compare it with the literature. We compared perioperative outcomes between minimally invasive adrenalectomy (MIA) and open adrenalectomy (OA). Methods: This retrospective study included patients who underwent adrenalectomy at five tertiary care centers in Saudi Arabia from 2010 to 2020. We collected patients' baseline and perioperative characteristics and detailed hormonal evaluation of adrenal masses. Results: Among 160 patients (mean age 44 ± 14.5 years; mean BMI 29.17 ± 5.96 kg/m2), 84 (51.5 %) were men and 51.5 % had left-sided adrenal masses. The mean tumor size was 6.1 ± 4.2 (1.0-19.5) cm, including 60 (37.5 %) incidentalomas and 65 (40.6 %) functioning masses. Histopathology revealed 74 (46.2 %) adenomas and 24 (15 %) cancers or metastases from other primary organs; 20 %, 8.8 %, and 2.5 % of patients had pheochromocytoma, myelolipoma, and 2.5 % ganglioneuroblastoma, respectively. MIA and OA were performed in 135 (84.4 %) and 21 (15.6 %) patients, respectively. Adrenalectomy was increasingly performed over three equal periods in the last decade (17.5 % vs 34.4 % vs 48.1 %), with increasing numbers of MIAs to replace OAs. OA patients had larger tumors and needed blood transfusion more frequently (47.6 % vs 10.8 %, p< 0.001). MIA was significantly associated with shorter operative time, shorter length of stay, and less blood loss. Postoperative complications occurred in 10 (6.2 %) patients and were significantly higher for OA (24 % vs 3.0 %, p< 0.001). Conclusions: The majority of adrenal masses are benign. Herein, the observed functional and perioperative outcomes were comparable to those of available meta-analyses.

Evaluation of the urology residency training program in Saudi Arabia: A cross-sectional study.

PURPOSE: This study evaluates the satisfaction of urology residents with the Saudi Board of Urology (SBU) Training Program and identifies areas of weakness and strength to improve the educational environment, surgical competency, and overall satisfaction of urology residents with the program. METHODS: We administered an electronic self-made questionnaire that included two sections. One comprised demographic data (age, gender, weight, height, marital status, level of training, city of training, and center of training), while the other concerned SBU evaluation (satisfaction with different aspects of training, such as ways of assessment, mentors' feedback, surgical competency, research, and strengths and weaknesses of SBU). RESULTS: The overall satisfaction of urology residency program was 28.8% while 44.2% of residents had a neutral response. The highest level of satisfaction with clinical and surgical practice was among graduates (56.9%) and Riyadh residents (45.1%). Furthermore, good work/life balance received the lowest level of satisfaction (5.2%) among senior residents, while good clinical experience received the highest level (62.7%) among the graduates. Residents reported a high exposure in endourology and pediatric urology, while transplant, reconstructive, and neurourology had the lowest exposure. Forty-two percent of respondents undertook research during their residency training, but most respondents (54%) did not publish any research papers during their training. Sixty-two percent of graduates felt that their training program did not prepare them adequately to perform well on the board examinations. CONCLUSION: Our results confirmed that satisfaction of residents with the urology program process is variable according to the city of training. Having high satisfaction level in some cities reflects the improvement of urology training program after restructuring. We identified new areas in need of improvement, namely lack of mentorship, clear and formal assessment process, and variation of training process between central and peripheral programs.

Testicular fibroma: A case report and literature review.

Sex cord-stromal tumors are the second most common testicular tumors after germ cell tumors. They account for about 2%-5% of adult testicular tumors. Most of these tumors are benign. The most common sex cord-stromal tumor is Leydig cell tumor. In contrast, testicular fibroma is a very rare type of sex cord-stromal tumors. Histologically, testicular fibromas resemble their ovarian counterparts; however, they are much less common than ovarian fibromas. To the best of our knowledge, <50 cases of testicular fibromas are reported in the English literature. Herein, we report a rare case of testicular fibroma with acellular collagen plaque in a 51-year-old male presenting as a painless testicular mass.

Urethral clear cell carcinoma - Case report and review of litrature.

Urethral clear cell carcinoma is very rare disease affecting both sexes, however it is mostly described in female urethra. The origin of this cancer is yet to be discovered. We report a 57 years old lady who presented to our clinic with obstructive lower urinary tract symptoms and found to have a urethral diverticulum containing a soft tissue lesion found to be a clear cell carcinoma after excision. Having high suspicion and early detection of these cases leads to a better outcome.

Robot-Assisted Radical Prostatectomy in Low-Volume Regions: Should It Be Abandoned or Adopted? A Multi-Institutional Outcome Study.

Purpose: To present multinational experience in robot-assisted radical prostatectomy (RARP) by fellowship-trained expertise in low-volume regions in Gulf Cooperation Council (GCC) countries and to compare the current results with global outcomes reported in recent meta-analyses. Methods: A retrospective review of prospectively collected data was performed for patients undergoing RARP for localized prostate cancer (PCa). Three fellowship-trained surgeons at four academic and referral centers in Saudi Arabia and Kuwait performed all procedures between February 2014 and December 2019. Data on demographics, perioperative characteristics, pathology, and adverse events were collected. Results: A total of 207 patients were included with a median (IQR) follow-up duration of 28 (15-38) months. The median prostate volume and prostate-specific antigen were 42 (32-53) g and 9.1 (5.8-14.1) ng/mL, respectively. While 65.2% of patients had a Gleason score ≥7, 20% had grade group 4 disease, and 7.8% had ≥cT3 disease. The mean ± SD operative time was 203 ± 52 minutes, and the mean estimated blood loss was 158 ± 107 mL. Only 4 (1.9%) patients received perioperative blood transfusions. Positive surgical margins were observed in 21.7% of patients, all of whom had ≥pT3 disease. There were 23 complications in 18 (8.7%) patients, including Clavien-Dindo grade III complications in 2.4%. At the 12-month follow-up, 35.8% of patients were potent, 94.6% were continent, and 9.2% had biochemical recurrence. Conclusions: The safety and efficacy of RARP by fellowship-trained expertise in GCC countries were well established. The outcomes seem promising and comparable to international centers and should improve with increasing case volume and fellowship-trained expertise.

The perception and competency of undergraduates in urology: Is the clinical exposure necessary?

OBJECTIVE: The objective of this study is to investigate medical students' perception, choices of future career, and competency in urology. METHODS: A cross-sectional survey was distributed among 5th, 6th, and 7th(interns) year medical students at King Saud bin Abdulaziz University for Health Sciences using both hard copies and soft copies. Major outcomes were medical students' perception, future career decision, and core skills in urology. RESULTS: The overall response rate was 51.3%. A total number of 163 responses (122 were males and 41 females) were collected. Only 8% indicated that they would pursue a surgical career in urology and 42% thought that they had received a good clinical exposure to urology. Of the participants, 67.5% viewed urology as a male-dominated field. Only 17% of the respondents either agreed or strongly agreed that they were considering a future career in urology. Female students were less likely to consider a urological career (P < 0.01). About 32.5% were confident at urethral catheterization. About 66.9% felt that a workshop day to enhance urological skills and knowledge will be beneficial. Females were more confident at assessing a urological case in an acute setting (P < 0.05). CONCLUSION: Most of the students agreed that their urology exposure was inadequate and their confidence at urethral catheterization was low. As in many different global studies, urology is still regarded as a specialty with a male dominance. This report is consistent with the global decline in formal urological education.

The grasper-integrated disposable flexible cystoscope is comparable to the reusable, flexible cystoscope for the detection of bladder cancer.

Flexible cystoscopy under local anaesthesia is standard for the surveillance of bladder cancer. Frequently, several reusable cystoscopes fail to reprocess. With the new grasper incorporated single-use cystoscope for retrieval of ureteric stents, we explored the feasibility of using it off-label for diagnosis and the detection of bladder cancer. Consecutive diagnostic flexible cystoscopies between Mar 2016 and Nov 2018 were reviewed comparing the reusable versus the disposable cystoscopes. A total of 390 patients underwent 1211 cystoscopies. Median age was 61.5 years (SD 14.2, 18.8-91.4), males 331 (84.9%) and females 59 (15.1%). Indication for cystoscopy was prior malignancy in 1183 procedures (97.7%), haematuria 19 (1.6%) or bladder mass 7 (0.6%). There were 608 reusable and 603 disposable cystoscopies. There was no significant difference between groups at baseline in age, sex, BMI, smoking status, or prior tumor risk category. There was no significant difference in positive findings (123/608, 20.2% vs 111/603, 18.4%, p = 0.425) or cancer detection rates (95/608, 15.6% vs 88/603, 14.4%, p 0.574) among the two groups, respectively. We conclude that the disposable grasper integrated cystoscope is comparable to reusable cystoscope in the detection of bladder cancer.

BRCA2 gene mutation and prostate cancer risk. Comprehensive review and update.

The second most common type of tumor worldwide is prostate cancer (PCa). Certain genetic factors contribute to a risk of developing PCa of as much as 40%. BRCA1 and BRCA2 mutations have linked with an increased risk for breast, ovarian, and PCa. However, BRCA2 is the most common gene found altered in early-onset of PCa in males younger than 65. BRCA2 mutation has a higher chance of developing an advanced stage of the disease, resulting in short survival time. This review aimed to describe the genetic changes in BRCA2 that contribute to the risk of PCa, to define its role in the early diagnosis in a man with a strong family history, and to outline the purpose of genetic testing and counseling. Also, the review summarizes the impact of BRCA2 gene mutation in localized PCa, and the treatment strategies have used for PCa patients with a BRCA2 modification.

Kidney cancer in Saudi Arabia. A 25-year analysis of epidemiology and risk factors in a tertiary center.

OBJECTIVES: To evaluate available epidemiological data and risk factors for kidney cancer in a tertiary care center in Riyadh, Saudi Arabia, over a period of 25 years. METHODS: This retrospective study conducted in a tertiary care center included all adult patients with primary kidney cancer who presented and were managed between 1990 and 2015. Based on this information, we forecast the incidence of the disease in our center over the next 5 years (2016 to 2020). RESULTS: In total, 371 patients were included in the study. The mean age of the patients was 56.3 years and the majority were male (61%). Among the patients, 55.8% were diagnosed incidentally. At the time of diagnosis, 53.2% were hypertensive, 46.2% were diabetic, 39.1% had dyslipidemia, and 25% were smokers. In addition, most patients were obese (42.3%) or overweight (30%). The most frequent histopathological variants were clear cell and chromophobe. Most patients presented with Stage 1. Minimally invasive surgery (laparoscopic, robotic) was performed in 55% of cases. Based on these data, we predicted that 172 new cases will present at our tertiary care center in 5 years from 2016 to 2020. CONCLUSION: The incidence in kidney cancer is increasing and is associated with an alarming increase in the prevalence of associated risk factors.

Does fasting in Ramadan increase the risk of developing urinary stones?

OBJECTIVES: To explore the frequency of renal colic (RC) secondary to urinary stones in Ramadan compared to other months and seasons of the year. METHODS: Retrospective cross-sectional study using medical records of 237 patients admitted through the emergency room (ER) with a diagnosis of RC secondary to urinary stones over a 10-year period at King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia. RESULTS: Patients fasting in Ramadan are 2 times more likely to present with a calculus of ureter as opposed to calculus in another location in the urinary tract, particularly when the holy month of Ramadan falls in the summer season. There was no significant difference in the frequency of urinary stones between Ramadan and non-Ramadan months. CONCLUSION: Fasting in Ramadan does not increase the risk for developing urinary stones compared to non-fasting months. However, fasting in Ramadan during the summer may increase the risk of developing ureter stones compared to fasting in Ramadan during the winter.

Epidemiology profile of renal cell carcinoma: A 10-year patients' experience at King Abdulaziz Medical City, National Guard Health Affairs, Saudi Arabia.

PURPOSE: The purpose of this study is to describe the epidemiological profile, histopathological features, and outcomes of patients diagnosed with renal cell carcinoma (RCC) in a tertiary referral center over 10 years. METHODOLOGY: This is a retrospective cohort of 219 Saudi patients diagnosed with RCC between June 2003 and May 2013. The variables collected included the sociodemographic details and clinical presentation. The histopathological features investigated include the tumors histological subtype, pathologic staging tumor, node, and metastasis descriptors, and lymph-vascular invasion. Patients were followed until May 2013. Bivariable analysis was calculated using Chi-square test, with level of significance set at P < 0.05. Kaplan-Meier estimate was used to calculate the survival rate. RESULTS: The mean age of patients was 57.18 (±14.68 standard deviation). The trend of patients diagnosed with RCC over the past 10 years was higher among males than females (60.27% vs. 39.73%). Noticeably, more than half (57.58%) were diagnosed incidentally. The most common histological subtype was clear cell (conventional) RCC (70.44%). Patients were usually diagnosed at the pT1 stage (48.1%).The histopathological features associated with worse patient outcome were the stage of the primary tumor (P = 0.01) and lymph-vascular invasion (P = 0.003). The overall mean survival rate was 2.03 years. CONCLUSION: In the past 10 years, there are more patients diagnosed incidentally with RCC, which is in line with the global trend. Patients were more likely to be male and middle aged. We recommend further population-based studies in this area to establish a national epidemiological data for this common type of cancer.

Characteristics of bladder neoplasms in the young population of Saudi Arabia.

CONTEXT: Bladder neoplasms are a well-studied subject in medicine. However, the evidence of bladder neoplasms in children and the young adult population (≤40 years), particularly in Saudi Arabia, is lacking. AIMS: The aims of this study were to identify histopathological characteristics as well as clinical features, prognosis, and treatment of bladder neoplasms in this age group in a single tertiary referral center, Riyadh, Saudi Arabia. SETTINGS AND DESIGN: A retrospective cohort study. MATERIALS AND METHODS: Children and young adults (≤40 years) diagnosed with epithelial and mesenchymal bladder neoplasms from 1994 to 2017. STATISTICAL ANALYSIS USED: Descriptive data are presented as mean (standard deviation) or median (interquartile range) for continuous variables and n (%) for categorical variables. Statistical Package for Social Sciences version 23 was used. RESULTS: Thirty-eight cases were identified. The majority, 71.1% (n = 27) were male. The median age of diagnosis was 33 years ranging from 1 to 40 years. Nearly 45% (n = 17) were smokers. Macroscopic hematuria was present in 57.8% (n = 22). The most common histopathology was papillary urothelial carcinoma (n = 18, 58%). All mesenchymal neoplasms accounted for 18.4% (n = 7). Of all malignancies, 63.2% (n = 24) and 44.7% (n = 17) were low stage and low grade, respectively. Transurethral resection of bladder tumor (TURBT) was conducted for 81.6% (n = 31). The mean length of follow-up was 36.05 months (±39.4 months). Recurrence occurred in 15.8% (n = 6) and 7.9% (n = 3) had progression. Distant metastasis was reported in 5.3% (n = 2). Nearly 8% (n = 3) died during their follow-up. CONCLUSIONS: Bladder malignancies at the early fourth decade of life tend to be a low stage and low grade. The most common histopathology was papillary urothelial carcinoma. Management should be based on the clinical and histopathological features. However, most of the patient underwent TURBT.

The prevalence of urinary tract infection, or urosepsis following transrectal ultrasound-guided prostate biopsy in a subset of the Saudi population and patterns of susceptibility to flouroquinolones.

OBJECTIVES: To study the prevalence of urinary tract infections (UTI), or sepsis secondary to trans-rectal ultrasound-guided (TRUS) biopsy of the prostate, the pathogens involved, and patterns of antibiotic resistance in a cohort of patients. METHODS: This is a descriptive study of a consecutive cohort of patients who underwent elective TRUS biopsy at King Abdulaziz Medical City, Riyadh, Saudi Arabia between January 2012 and December 2014. All patients who underwent the TRUS guided prostate biopsy were prescribed the standard prophylactic antibiotics. Variables included were patients' demographics, type of antibiotic prophylaxis, results of biopsy, the rate of UTI, and urosepsis with the type of pathogen(s) involved and its/their antimicrobial sensitivity.  RESULTS: Simple descriptive statistics were used in a total of 139 consecutive patients. Urosepsis requiring hospital admission was encountered in 7 (5%) patients and uncomplicated UTI was observed in 4 (2.8%). The most common pathogens were Escherichia coli (90.1%) and Klebsiella pneumoniae (9.1%). Resistance to the routinely used prophylaxis (ciprofloxacin) was observed in 10 of these patients (90.9%). CONCLUSION: This showed an increase in the rate of infectious complications after TRUS prostate biopsy. Ciprofloxacin resistance was found in 90.9% of patients with no sepsis.

A case report of a xanthogranulomatous pyelonephritis case mimicking the recurrence of renal cell carcinoma after partial nephrectomy.

A 44-year-old female presented to the urology clinic with flank pain and tenderness. After full assessment, the patient was booked for surgery for partial nephrectomy and the patient was diagnosed with renal cell carcinoma (RCC) chromophob type. Six months later, the patient came back for follow-up; a mass was detected on the same kidney. Radical nephrectomy was performed to excise what is thought to be a recurrence of RCC and the tissues were sent to pathology. The postoperative pathology report confirmed the presence of xanthogranulomatous pyelonephritis rather than RCC recurrence.

Increasing trends in kidney cancer over the last 2 decades in Saudi Arabia.

OBJECTIVES: To examine the trends of kidney cancer over the last 2 decades in a subset of a Saudi Arabian population.   METHODS: We conducted a retrospective study in a tertiary care center including all adult patients with primary kidney cancer who presented and were managed between 1990 and 2010. The time period was split into 4 quartiles, and variables tested and compared using chi-square, T-test, and Kaplan-Meier curves for survival.   RESULTS: The total was 215 patients with a mean age of 57.8 years. There was an increase in the number of kidney cancer cases over the last 2 decades. There was no significant difference in the mode of presentation or stage distribution between quartiles. A significant change was observed in the management towards minimally invasive and nephron-sparing surgeries (p less than 0.001). There was no change in recurrence-free and disease-specific survival over the last 20 years.   CONCLUSIONS: There have been an increasing number of kidney cancer patients over the last 2 decades with no observed migration towards more incidental and low stage tumors as compared with developed countries.

Prognostic value of molecular markers, sub-stage and European Organisation for the Research and Treatment of Cancer risk scores in primary T1 bladder cancer.

UNLABELLED: What's known on the subject? and What does the study add? The stakes are high when making treatment decisions in T1 bladder cancer (BC). Conservative management may lead to progression and possibly death from BC. Conversely, radical cystectomy could be over-treatment of non-progressive disease. The problem for clinicians is that reliable prognostic indices are lacking. We performed a head-to-head comparison of two substaging systems, European Organisation for the Research and Treatment of Cancer (EORTC) risk scores and four molecular markers in T1 carcinomas of the bladder treated conservatively with BCG. T1 sub-stage according to a new system (micro-invasive [T1m] and extensive-invasive [T1e]) was the most important clinical variable for predicting progression to carcinoma invading bladder muscle. The performance of the EORTC risk scores was disappointing for this T1 sub-group. Molecular markers were not significant in multivariable analysis for predicting progression. Future studies may lead to the incorporation of sub-stage (T1m/T1e) in the TNM classification system for urinary BC to guide clinical decision-making in T1 BC. OBJECTIVE: To evaluate the prognostic significance of four molecular markers, sub-stage and European Organisation for the Research and Treatment of Cancer (EORTC) risk scores in primary T1 bladder cancer (BC) treated with adjuvant bacille Calmette-Guérin. PATIENTS AND METHODS: The slides of 129 carcinomas of the bladder from two university hospitals were reviewed and the T1 diagnosis was confirmed. T1 sub-staging was done in two separate rounds, using a new system that identifies micro-invasive (T1m) and extensive-invasive (T1e) T1BC, and then according to invasion of the muscularis mucosae (T1a/T1b/T1c). The EORTC risk scores for recurrence and progression were calculated. Uni- and multivariable analyses for recurrence and progression were performed using clinicopathological variables, T1 sub-stage, EORTC risk scores and molecular markers (fibroblast growth factor receptor 3 gene mutation and Ki-67, P53, P27 expression). RESULTS: The median follow-up was 6.5 years. Forty-two patients remained recurrence-free (33%). Progression to T2 or metastasis was observed in 38 (30%) patients. In multivariable analysis for recurrence, multiplicity was significant. In multivariable analysis for progression, female gender, sub-stage (T1m/T1e) and carcinoma in situ (CIS) were significant. Molecular markers were significant in univariable and in multivariable analyses for recurrence. EORTC risk scores were not significant. CONCLUSIONS: CIS, female gender and sub-stage (T1m/T1e) were the most important variables for progression. The additional value of molecular markers was modest. Sub-stage (T1m/T1e) could potentially be incorporated in future tumour-node-metastasis classifications.

The FGFR3 mutation is related to favorable pT1 bladder cancer.

PURPOSE: Stage pT1 bladder cancer comprises a heterogeneous group of tumors for which different management options are advocated. FGFR3 mutations are linked to favorable (low grade/stage) pTa bladder cancer while altered P53 is common in cases of high grade, muscle invasive (pT2 or greater) bladder cancer. We determined the frequency of FGFR3 mutations and P53 alterations in patients with pT1 bladder cancer and correlated these data to histopathological variables and clinical outcomes. MATERIALS AND METHODS: We included 132 patients with primary pT1 bladder cancer from a total of 2 academic centers. A uropathologist reviewed the slides for grade and confirmed the pT1 diagnosis. FGFR3 mutation status was examined by SNaPshot® analysis and P53 expression was determined by standard immunohistochemistry. Kaplan-Meier and multivariate analyses were used to assess progression. RESULTS: FGFR3 mutations were detected in 37 of 132 pT1 bladder cancer cases (28%) and altered P53 was seen in 71 (54%). Only 8% of patients had the 2 molecular alterations (p = 0.001). FGFR3 mutation correlated with lower grade and altered P53 correlated with high grade pT1 bladder cancer. Median followup was 6.5 years. FGFR3 mutation status and carcinoma in situ were significant for predicting progression on univariate and multivariate analyses but P53 status was not. CONCLUSIONS: FGFR3 mutations selectively identify patients with pT1 bladder cancer who have favorable disease characteristics. Further study may confirm that FGFR3 identifies those who would benefit from a conservative approach to the disease.

A new and highly prognostic system to discern T1 bladder cancer substage.

BACKGROUND: Management of T1 bladder cancer (BCa) is controversial. OBJECTIVE: Evaluate the impact of substage on the clinical outcome of T1 BCa. DESIGN, SETTING, AND PARTICIPANTS: The T1 diagnosis of 134 first-diagnosis BCa patients from two university hospitals was confirmed. For the T1 substage, we used a new system that discerns T1-microinvasive (T1m) and T1-extensive-invasive (T1e) tumors. We then determined the invasion of the muscularis mucosae-vascular plexus (MM-VP): T1a (invasion above the MM-VP), T1b (invasion in the MM-VP), or T1c (invasion beyond the MM-VP). If the MM-VP was not present at the invasion front, the case was assigned to T1a or T1c. All patients were initially managed conservatively (with bacillus Calmette-Guérin). MEASUREMENTS: Multivariable analyses for progression and disease-specific survival (DSS). RESULTS AND LIMITATIONS: Median follow-up was 6.4 yr (interquartile range: 3.3-9.2 yr). Progression to ≥ T2 was observed in 40 patients (30%), and 19 patients (14%) died of BCa. The MM-VP was not present at the invasion front in 50 patients (37%). T1 substage was as follows: 40 T1m and 94 T1e; 81 T1a, 18 T1b, and 35 T1c. In multivariable analyses, substage (T1m/T1e) was significant for progression (p=0.001) and DSS (p=0.032), whereas substage according to T1a/T1b/T1c was not significant. Female gender (p=0.006) and carcinoma in situ (p=0.034) were also significant predictors of progression. The main limitation to the study is absence of a repeat transurethral resection. CONCLUSIONS: Substage according to the new system (T1m and T1e) was user-friendly, possible in 100% of cases, and very predictive of T1 BCa behavior. Future studies may ultimately lead to the incorporation of this new substaging system in the TNM classification system for urinary BCa.

Long-term prognostic value of the combination of EORTC risk group calculator and molecular markers in non-muscle-invasive bladder cancer patients treated with intravesical Bacille Calmette-Guérin.

BACKGROUND AND OBJECTIVES: To evaluate the long-term prognostic value of the combination of the EORTC risk calculator and proapoptotic, antiapoptotic, proliferation, and invasiveness molecular markers in predicting the outcome of intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC) treated with intravesical Bacille Calmette-Guérin (BCG) therapy. MATERIALS AND METHODS: This study included 42 patients accrued prospectively presenting with intermediate- to high-risk NMIBC (high-grade T1 tumors or multiple rapidly recurrent tumors refractory to intravesical chemotherapy) treated with transurethral resection (TUR) and BCG. TUR samples were analyzed for the molecular markers p53, p21 waf1/cip, Bcl-2, CyclinD1, and metallothionein 9 (MMP9) using immunohistochemistry. Frequency of positivity, measured as a percentage, was assessed alone or in combination with EORTC risk calculator, for interaction with outcome in terms of recurrence and progression using univariate analysis and Kaplan-Meier survival curves. RESULTS: Median follow-up was 88 months (mean, 99; range, 14-212 months). The overall recurrence rate was 61.9% and progression rate was 21.4%. In univariate analysis, CyclinD1 and EORTC risk groups were significantly associated with recurrence (P value 0.03 and 0.02, respectively), although none of the markers showed a correlation to progression. In combining EORTC risk groups to markers expression status, high-risk group associated with positive MMP9, Bcl-2, CyclinD1, or p21 was significantly correlated to tumor recurrence (log rank P values <0.001, 0.03, 0.02, and 0.006, respectively) and when associated with positive MMP9 or p21, it was significantly correlated to progression (log rank P values 0.01 and 0.04, respectively). CONCLUSION: Molecular markers have a long-term prognostic value when combined with EORTC scoring system and they may be used to improve the predictive accuracy of currently existing scoring system. Larger series are needed to confirm these findings.