Publications by authors named "Sultan S AlKhateeb"

19 Publications

  • Page 1 of 1

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

Urol Case Rep 2021 Sep 29;38:101659. Epub 2021 Mar 29.

King Faisal Specialist Hospital and Research Center, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.

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.
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http://dx.doi.org/10.1016/j.eucr.2021.101659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047157PMC
September 2021

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

J Endourol 2021 Feb 23. Epub 2021 Feb 23.

Department of Urology, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia.

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. 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. 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. 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.
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http://dx.doi.org/10.1089/end.2020.0770DOI Listing
February 2021

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

Urol Ann 2020 Jul-Sep;12(3):220-224. Epub 2020 Jun 10.

Department of Urology, King Faisal Specialist Hospital and Research Centre, Alfaisal University Riyadh, Riyadh, Saudi Arabia.

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 5, 6, and 7(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 ( < 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 ( < 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.
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http://dx.doi.org/10.4103/UA.UA_39_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546068PMC
June 2020

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

Sci Rep 2020 08 10;10(1):13495. Epub 2020 Aug 10.

Department of Urology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.

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.
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http://dx.doi.org/10.1038/s41598-020-70424-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7417573PMC
August 2020

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

Saudi Med J 2020 Jan;41(1):9-17

Department of Urology, King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia. E-mail.

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.
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http://dx.doi.org/10.15537/smj.2020.1.24759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001059PMC
January 2020

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

Saudi Med J 2018 May;39(5):481-486

College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia. E-mail.

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.
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http://dx.doi.org/10.15537/smj.2018.5.22160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6118172PMC
May 2018

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

Saudi Med J 2018 May;39(5):459-463

King Saud bin Abdulaziz University for Health Sciences, College of Medicine, Riyadh, Kingdom of Saudi Arabia. E-mail.

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.
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http://dx.doi.org/10.15537/smj.2018.5.22641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6118183PMC
May 2018

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

Urol Ann 2018 Jan-Mar;10(1):59-64

Department of Surgery, Division of Urology, King Abdulaziz Medical City, Riyadh, 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 < 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 ( = 0.01) and lymph-vascular invasion ( = 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.
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http://dx.doi.org/10.4103/UA.UA_102_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5791459PMC
February 2018

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

Urol Ann 2017 Oct-Dec;9(4):343-347

Department of Urology, King Abdulaziz Medical City, Riyadh, 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 (%) for categorical variables. Statistical Package for Social Sciences version 23 was used.

Results: Thirty-eight cases were identified. The majority, 71.1% ( = 27) were male. The median age of diagnosis was 33 years ranging from 1 to 40 years. Nearly 45% ( = 17) were smokers. Macroscopic hematuria was present in 57.8% ( = 22). The most common histopathology was papillary urothelial carcinoma ( = 18, 58%). All mesenchymal neoplasms accounted for 18.4% ( = 7). Of all malignancies, 63.2% ( = 24) and 44.7% ( = 17) were low stage and low grade, respectively. Transurethral resection of bladder tumor (TURBT) was conducted for 81.6% ( = 31). The mean length of follow-up was 36.05 months (±39.4 months). Recurrence occurred in 15.8% ( = 6) and 7.9% ( = 3) had progression. Distant metastasis was reported in 5.3% ( = 2). Nearly 8% ( = 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.
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http://dx.doi.org/10.4103/UA.UA_122_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5656959PMC
November 2017

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.

Saudi Med J 2016 Aug;37(8):860-3

Department of Urology, King Abdulaziz Medical City, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia. E-mail.

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.
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http://dx.doi.org/10.15537/smj.2016.8.15803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5018702PMC
August 2016

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

Urol Ann 2015 Oct-Dec;7(4):524-6

Department of Urology, King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia.

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.
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http://dx.doi.org/10.4103/0974-7796.164857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4660711PMC
December 2015

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

Saudi Med J 2015 Jul;36(7):885

Division of Urology, Department of Surgery, King Abdulaziz Medical City, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia. E-mail.

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July 2015

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

Saudi Med J 2015 Jun;36(6):698-703

Division of Urology, Department of Surgery, King Abdulaziz Medical City, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia. E-mail.

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.
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http://dx.doi.org/10.15537/smj.2015.6.10841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4454904PMC
June 2015

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

BJU Int 2012 Oct 27;110(8):1169-76. Epub 2012 Mar 27.

Division of Urology, University Health Network, Princess Margaret Hospital, Toronto, ON, Canada.

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.
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http://dx.doi.org/10.1111/j.1464-410X.2012.10996.xDOI Listing
October 2012

The FGFR3 mutation is related to favorable pT1 bladder cancer.

J Urol 2012 Jan 17;187(1):310-4. Epub 2011 Nov 17.

Division of Urology, Princess Margaret Hospital, Toronto, Ontario, Canada.

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.
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http://dx.doi.org/10.1016/j.juro.2011.09.008DOI Listing
January 2012

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

Eur Urol 2012 Feb 25;61(2):378-84. Epub 2011 Oct 25.

Department of Surgical Oncology, Division of Urology, University Health Network, Princess Margaret Hospital, Toronto, Canada.

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.
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http://dx.doi.org/10.1016/j.eururo.2011.10.026DOI Listing
February 2012

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.

Urol Ann 2011 Sep;3(3):119-26

Department of Surgical Oncology, Princess Margaret Hospital, University Health Network, Toronto, Canada.

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.
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http://dx.doi.org/10.4103/0974-7796.84954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3183702PMC
September 2011

Diminished efficacy of Bacille Calmette-Guérin among elderly patients with nonmuscle invasive bladder cancer.

Urology 2011 Oct 16;78(4):848-54. Epub 2011 Aug 16.

Department of Surgical Oncology, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada.

Objective: Bacille Calmette-Guérin (BCG) is recommended as adjunctive therapy among patients with high-risk nonmuscle-invasive bladder cancer (BC). Given that immune response is attenuated with age, we set out to determine the impact of age on response to BCG.

Materials And Methods: We searched our prospective bladder information system and limited our search to patients with incident BC completely resected at transurethral resection (TUR) who completed a full induction course of BCG. We then analyzed the impact of age on outcome. Age was analyzed both dichotomously (greater or less than 75 years) as well as by 10-year increments. The main outcomes were recurrence or progression-free survival. Log-rank and multivariable Cox proportional-hazard analyses, adjusting for clinical and pathologic features (age, multifocality, pathologic stage, grade and associated carcinoma in situ, maintenance, and restaging) were used.

Results: This cohort included 238 patients. Baseline parameters were similar aside from tumor number. Progression-free survival differed between age groups when examined either dichotomously or via 10-year increments. The 2-year progression-free survival was 87% among patients <75 years vs 65% in patients >75 years (log rank P <.001). An age-dependent trend was noted when analyzed by 10-year increment (log-rank for trend P = .011). On multivariable analysis, age was an independent risk factor for progression (HR = 2.9, 95% CI 1.7-4.9). Recurrence-free survival was similar among age strata.

Conclusion: We demonstrated that advanced age is associated with higher progression rates despite BCG. The care of BC in the elderly population is of increasing concern and should be addressed in a prospective clinical study.
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http://dx.doi.org/10.1016/j.urology.2011.04.070DOI Listing
October 2011

Nonprimary pT1 nonmuscle invasive bladder cancer treated with bacillus Calmette-Guerin is associated with higher risk of progression compared to primary T1 tumors.

J Urol 2010 Jul 15;184(1):81-6. Epub 2010 May 15.

Division of Urology, Department of Surgical Oncology, Princess Margaret Hospital, University Health Network, Toronto, Canada.

Purpose: Few studies have examined the prognostic significance of prior tumor resection(s) in cases of T1 nonmuscle invasive bladder cancer treated with intravesical bacillus Calmette-Guerin. We examined this issue by comparing the prognosis of primary vs nonprimary T1 nonmuscle invasive bladder cancer treated with bacillus Calmette-Guerin.

Materials And Methods: Patients with pT1 nonmuscle invasive bladder cancer treated with bacillus Calmette-Guerin were identified and tumor pathology was reviewed. Patients were then stratified into primary vs nonprimary tumors, and outcomes were compared using univariate, multivariate and Kaplan-Meier survival analyses, and the Cox regression model adjusting for various clinical and pathological features including, age, gender, tumor size, multifocality, pathological grade and associated carcinoma in situ.

Results: The study included 191 patients, 95 (49.7%) with primary and 96 (50.3%) with nonprimary tumors. The clinical and pathological characteristics were comparable. For the primary vs the nonprimary group progression rates were 24.2% vs 39.6%, respectively (HR 2.07, 95% CI 0.98-3.71, multivariate p = 0.03) and the 5-year progression-free survival rates were 71.9% vs 51.5%, respectively (log rank p <0.001). This difference remained significant on multivariate Cox regression analysis (HR 2.53, 95% CI 1.40-4.57, p = 0.002). There was no difference between the groups in recurrence or disease specific mortality.

Conclusions: Nonprimary T1 nonmuscle invasive bladder tumors treated with bacillus Calmette-Guerin carry a significantly higher risk of progression to muscle invasive disease compared to primary tumors. This information may be used in combination with other prognostic factors to identify those at high risk for progression when counseling patients.
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http://dx.doi.org/10.1016/j.juro.2010.03.022DOI Listing
July 2010