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ABSTRACT: Clinical variables with more accuracy to predict biologically insignificant prostate cancer are needed. We evaluated the combination of transrectal ultrasound-guided biopsy of the prostate (TRUSBx) pathologic and radiologic findings in their ability to predict the biologic potential of each prostate cancer.
A total of 1043 consecutive patients who underwent TRUSBx were reviewed. Using pathologic criteria, patients with prostate cancer (n = 529) and those treated with radical prostatectomy (RP) (n = 147) were grouped as: "insignificant" (Gleason score ≤ 6, prostate-specific antigen (PSA) density ≤ 0.15 ng/ml, tumor in ≤ 50% of any single core, and < 33% positive cores) and "significant" prostate cancer. TRUSBx imaging and pathology results were compared with the RP specimen to identify factors predictive of "insignificant" prostate cancer.
TRUSBx pathology results demonstrated perineural invasion in 36.4% of "significant" versus 5.4% of "insignificant" prostate cancers (p < 0.01) and pathologic invasion of periprostatic tissue in 7% of significant versus 0% of insignificant prostate cancers (p < 0.01). TRUS findings concerning for neoplasia were associated with significant tumors (p < 0.01). Multivariable analysis demonstrated perineural invasion in the biopsy specimen (p = 0.03), PSA density (p = 0.02) and maximum tumor volume of any core (p = 0.02) were independently predictive of a significant prostate cancer.
TRUS findings concerning for measurable tumor and perineural invasion in TRUSBx specimens appear to be complementary to Epstein's pathologic criteria and should be considered to aid in the determination whether a prostate cancer is organ-confined and more likely to be biologically insignificant.
The Canadian Journal of Urology 04/2013; 20(2):6696-701. · 0.64 Impact Factor
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Andrew K Williams,
Wassim Kassouf,
Joseph Chin,
Ricardo Rendon,
Niels Jacobsen,
Adrian Fairey,
Anil Kapoor,
Peter Black,
Louis Lacombe,
Simon Tanguay,
Alan So,
Jean-Baptiste Lattouf,
David Bell,
Yves Fradet,
Fred Saad,
Ed Matsumoto,
Darrel Drachenberg,
Ilias Cagiannos, Jonathan I Izawa
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ABSTRACT: OBJECTIVES: Whether a patient has urothelial carcinoma located within the renal pelvis or ureter remains a controversial prognostic indicator in clinical urology. We wished to evaluate whether tumor location is associated with recurrence in patients undergoing nephroureterectomy for upper tract urothelial cancer in a large volume patient cohort. SUBJECTS AND METHODS: We created a retrospective database of patients from 7 academic centers throughout Canada who underwent nephroureterectomy for upper tract urothelial carcinoma. Patient demographics as well as pathologic and surgical factors were analyzed to evaluate any statistical association between tumor location and overall survival, disease-free survival, and disease-specific survival. RESULTS: A total of 1,029 patients had data available for analysis with a mean follow up of 3.2 years. Kaplan Meier 5-year disease-free survivals (DFS) were 46%, 37%, and 19% for renal pelvis tumors, ureteric tumors, and multifocal tumors respectively. There was no association between the location of the tumor and the DFS, however, disease involving both the ureter and renal pelvis was associated with lower DFS and overall survival (OS) (P < 0.001). CONCLUSIONS: Tumor location does not appear to have any influence on the risk of recurrence of disease following nephroureterectomy in this large patient cohort. However, multifocal tumors involving both the ureter and renal pelvis had a significantly worse prognosis and should be considered for more aggressive management.
Urologic Oncology 02/2013; · 3.22 Impact Factor
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Thomas F Chromecki,
Eugene K Cha,
Harun Fajkovic,
Michael Rink,
Behfar Ehdaie,
Robert S Svatek,
Pierre I Karakiewicz,
Yair Lotan,
Derya Tilki,
Patrick J Bastian, [......],
Wassim Kassouf,
Matthieu Durand,
Giacomo Novara,
Hans-Martin Fritsche,
Maximilian Burger, Jonathan I Izawa,
Antonin Brisuda,
Marek Babjuk,
Karl Pummer,
Shahrokh F Shariat
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ABSTRACT: Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Little is known on the association between obesity and urothelial carcinoma of the bladder (UCB). Most studies have shown that higher body mass index (BMI) is associated with higher rates of perioperative complications. Only one study specifically investigated obesity and bladder cancer-specific outcomes and reported no significant association between higher BMI and disease-specific survival in patients with UCB treated with radical cystectomy. However, that study was limited by its small sample size and a high rate of preoperative therapies. In contrast to the only previous study evaluating the association of BMI with oncological outcomes in UCB, we found that obesity (BMI ≥30 kg/m(2) ) was associated with features of biologically aggressive UCB and clinical outcomes after radical cystectomy and, even when adjusting for the effects of standard clinicopathological features, obesity remained an independent predictor of cancer recurrence, cancer-specific mortality and overall mortality. OBJECTIVE: • To investigate the association between body mass index (BMI) and oncological outcomes in patients after radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) in a large multi-institutional series. PATIENTS AND METHODS: • Data were collected from 4118 patients treated with RC and pelvic lymphadenectomy for UCB. Patients receiving preoperative chemotherapy or radiotherapy were excluded. • Univariable and multivariable models tested the effect of BMI on disease recurrence, cancer-specific mortality and overall mortality. • BMI was analysed as a continuous and categorical variable (<25 vs 25-29 vs ≥30 kg/m(2) ). RESULTS: • Median BMI was 28.8 kg/m(2) (interquartile range 7.9); 25.3% had a BMI <25 kg/m(2) , 32.5% had a BMI between 25 and 29.9 kg/m(2) , and 42.2% had a BMI ≥30 kg/m(2) . • Patients with a higher BMI were older (P < 0.001), had higher tumour grade (P < 0.001), and were more likely to have positive soft tissue surgical margins (P = 0.006) compared with patients with lower BMI. • In multivariable analyses that adjusted for the effects of standard clinicopathological features, BMI >30 was associated with higher risk of disease recurrence (hazard ratio (HR) 1.67, 95% confidence interval (CI) 1.46-1.91, P < 0.001), cancer-specific mortality (HR 1.43, 95% CI 1.24-1.66, P < 0.001), and overall mortality (HR 1.81, CI 1.60-2.05, P < 0.001). The main limitation is the retrospective design of the study. CONCLUSIONS: • Obesity is associated with worse cancer-specific outcomes in patients treated with RC for UCB. • Focusing on patient-modifiable factors such as BMI may have significant individual and public health implications in patients with invasive UCB.
BJU International 06/2012; · 2.84 Impact Factor
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ABSTRACT: Transrectal ultrasound-guided needle biopsy of the prostate (TRUS) is a well-tolerated and standardized procedure for the diagnosis of prostate cancer. Complications associated with TRUS requiring emergency room visits or hospital admissions are relatively low and include complications, such as a 1% risk of urinary retention and less than 1% chance of bacterial sepsis. Vertebral osteomyelitis is a rare complication of TRUS; there are 3 reported cases. Vertebral osteomyelitis has an insidious onset and usually resolves following medical intervention. We present an extremely rare case of vertebral osteomyelitis following TRUS, its clinical outcome and management.
Canadian Urological Association journal = Journal de l'Association des urologues du Canada 02/2012; 6(1):E20-2. · 1.24 Impact Factor
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Shahrokh F Shariat,
Behfar Ehdaie,
Michael Rink,
Eugene K Cha,
Robert S Svatek,
Thomas F Chromecki,
Harun Fajkovic,
Giacomo Novara,
Scott G David,
Siamak Daneshmand, [......],
Hans-Martin Fritsche,
Maximilian Burger, Jonathan I Izawa,
Derya Tilki,
Firas Abdollah,
Felix K Chun,
Guru Sonpavde,
Pierre I Karakiewicz,
Douglas S Scherr,
Mithat Gonen
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ABSTRACT: Radical cystectomy (RC) with pelvic lymph node dissection (LND) is the standard of care for refractory non-muscle-invasive and muscle-invasive bladder cancer. Although consensus exists on the need for LND, its extent is still debated.
To develop a model that allows preoperative determination of the minimum number of lymph nodes (LNs) needed to be removed at RC to ensure true nodal status.
We analyzed data from 4335 patients treated with RC and pelvic LND without neoadjuvant chemotherapy at 12 academic centers located in the United States, Canada, and Europe.
We estimated the sensitivity of pathologic nodal staging using a beta-binomial model and developed clinical (preoperative) nodal staging scores (cNSS), which represent the probability that a patient has LN metastasis as a function of the number of examined nodes.
The probability of missing a positive LN decreased with an increasing number of nodes examined (52% if 3 nodes were examined, 40% if 5 were examined, and 26% if 10 were examined). A cNSS of 90% was achieved by examining 6 nodes for clinical Ta-Tis tumors, 9 nodes for cT1 tumors, and 25 nodes for cT2 tumors. In contrast, examination of 25 nodes provided only 77% cNSS for cT3-T4 tumors. The study is limited due to its retrospective design, its multicenter nature, and a lack of preoperative staging parameters.
Every patient treated with RC for bladder cancer needs an LND to ensure accurate nodal staging. The minimum number of examined LNs for adequate staging depends preoperatively on the clinical T stage. Predictive tools can give a preoperative estimation of the likelihood of nodal metastasis and thereby allow tailored decision-making regarding the extent of LND at RC.
European urology 02/2012; 61(2):237-42. · 7.67 Impact Factor
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ABSTRACT: To perform complete resection of locally advanced and recurrent rectal carcinoma, total pelvic exenteration (TPE) may be attempted. We identified disease-related outcomes and prognostic factors.
We conducted a single-centre review of patients who underwent TPE for rectal carcinoma over a 10-year period.
We included 28 patients in our study. After a median follow-up of 35 months, 53.6% of patients were alive with no evidence of disease. The 3-year actuarial disease-free and overall survival rates were 52.2% and 75.1%, respectively. On univariate analysis, recurrent disease, preoperative body mass index greater than 30 and lymphatic invasion were poor prognostic factors for disease-free survival, and only lymphatic invasion predicted overall survival. Additionally, multivariate analysis identified lymphatic invasion as an independent poor prognostic factor for disease-free survival in this patient population with locally advanced and recurrent rectal carcinoma.
Despite the significant morbidity, TPE can provide long-term survival in patients with rectal carcinoma. Additionally, lymphatic invasion on final pathology was an independent prognostic factor for disease-free survival.
Canadian journal of surgery. Journal canadien de chirurgie 10/2011; 54(6):387-93. · 1.05 Impact Factor
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Chen Lu,
Mark S McFarland,
Rae-Lynn Nesbitt,
Andrew K Williams,
Susanne Chan,
Jose Gomez-Lemus,
Anna Maria Autran-Gomez,
Ali Al-Zahrani,
Joseph L Chin, Jonathan I Izawa,
Leonard G Luyt,
John D Lewis
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ABSTRACT: Ghrelin is a natural growth hormone secretagogue (GHS) that is co-expressed with its receptor GHSR in human prostate cancer (PCa) cells. Imaging probes that target receptors for ghrelin may delineate PCas from benign disease. The specificity of a novel ghrelin-imaging probe for PCa over normal tissue or benign disease was assessed.
A fluorescein-bearing ghrelin analogue was synthesized (fluorescein-ghrelin(1-18)), and its application for imaging was evaluated in a panel of PCa cell lines and human prostate tissue. Prostate core biopsy samples were collected from fresh surgery specimens of 13 patients undergoing radical prostatectomy. Ghrelin probe signal was detected and quantified in each sample using a hapten amplification technique and associated with pathological features.
The ghrelin probe was taken up by GHSR-expressing LNCaP and PC-3 cells, and not in BPH cells that express low levels of GHSR. Binding was blocked by competition with excess unlabeled probe. The ghrelin probe signal was 4.7 times higher in PCa compared to benign hyperplasia tissue (P = 0.0027) and normal tissue (P = 0.0093). Furthermore, while the ghrelin probe signal was 1.9-fold higher in PIN compared to benign hyperplasia (P = 0.0022) and normal tissue (P = 0.0047), there was no significant difference in the signal of benign hyperplasia compared to normal tissue.
The imaging probe fluorescein-ghrelin(1-18) is specific for PCa, and did not associate significantly with benign hyperplasia or normal prostate tissue. This data suggests that ghrelin analogues may be useful as molecular imaging probes for prostatic neoplasms in both localized and metastatic disease.
The Prostate 09/2011; 72(8):825-33. · 3.48 Impact Factor
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Canadian Urological Association journal = Journal de l'Association des urologues du Canada 08/2011; 5(4):235-40. · 1.24 Impact Factor
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Philipp Nuhn,
Patrick J Bastian,
Giacomo Novara,
Robert S Svatek,
Pierre I Karakiewicz,
Eila Skinner,
Yves Fradet, Jonathan I Izawa,
Wassim Kassouf,
Francesco Montorsi,
Stefan C Müller,
Hans-Martin Fritsche,
Guru Sonpavde,
Derya Tilki,
Hendrik Isbarn,
Vincenzo Ficarra,
Colin P Dinney,
Shahrokh F Shariat
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ABSTRACT: The aim of this study was to externally validate the prognostic value of concomitant urothelial carcinoma in situ (CIS) in radical cystectomy (RC) specimens using a large international cohort of bladder cancer patients.
The records of 3,973 patients treated with RC and bilateral lymphadenectomy for urothelial carcinoma of the bladder (UCB) at nine centers worldwide were reviewed. Surgical specimens were evaluated by a genitourinary pathologist at each center. Uni- and multivariable Cox regression models addressed time to recurrence and cancer-specific mortality after RC.
1,741 (43.8%) patients had concomitant CIS in their RC specimens. Concomitant CIS was more common in organ-confined UCB and was associated with lymphovascular invasion (p < 0.001). Concomitant CIS was not associated with either disease recurrence or cancer-specific death regardless of pathologic stage. The presence of concomitant CIS did not improve the predictive accuracy of standard predictors for either disease recurrence or cancer-specific death in any of the subgroups.
We could not confirm the prognostic value of concomitant CIS in RC specimens. This, together with the discrepancy between pathologists in determining the presence of concomitant CIS at the morphologic level, limits the clinical utility of concomitant CIS in RC specimens for clinical decision-making.
Urologia Internationalis 06/2011; 87(1):42-8. · 0.99 Impact Factor
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Fatma Valiyeva,
Fei Jiang,
Ahmed Elmaadawi,
Madeleine Moussa,
Siu-Pok Yee,
Leda Raptis, Jonathan I Izawa,
Burton B Yang,
Norman M Greenberg,
Fen Wang,
Jim W Xuan
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ABSTRACT: A novel TRIM family member, TRIM59 gene was characterized to be upregulated in SV40 Tag oncogene-directed transgenic and knockout mouse prostate cancer models as a signaling pathway effector. We identified two phosphorylated forms of TRIM59 (p53 and p55) and characterized them using purified TRIM59 proteins from mouse prostate cancer models at different stages with wild-type mice and NIH3T3 cells as controls. p53/p55-TRIM59 proteins possibly represent Ser/Thr and Tyr phosphorylation modifications, respectively. Quantitative measurements by ELISA showed that the p-Ser/Thr TRIM59 correlated with tumorigenesis, whereas the p-Tyr-TRIM59 protein correlated with advanced cancer of the prostate (CaP). The function of TRIM59 was elucidated using short hairpin RNA (shRNA)-mediated knockdown of the gene in human CaP cells, which caused S-phase cell-cycle arrest and cell growth retardation. A hit-and-run effect of TRIM59 shRNA knockdown was observed 24 hours posttransfection. Differential cDNA microarrray analysis was conducted, which showed that the initial and rapid knockdown occurred early in the Ras signaling pathway. To confirm the proto-oncogenic function of TRIM59 in the Ras signaling pathway, we generated a transgenic mouse model using a prostate tissue-specific gene (PSP94) to direct the upregulation of the TRIM59 gene. Restricted TRIM59 gene upregulation in the prostate revealed the full potential for inducing tumorigenesis, similar to the expression of SV40 Tag, and coincided with the upregulation of genes specific to the Ras signaling pathway and bridging genes for SV40 Tag-mediated oncogenesis. The finding of a possible novel oncogene in animal models will implicate a novel strategy for diagnosis, prognosis, and therapy for cancer.
Molecular Cancer Therapeutics 05/2011; 10(7):1229-40. · 5.23 Impact Factor
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Wassim Kassouf,
Robert S Svatek,
Shahrokh F Shariat,
Giacomo Novara,
Seth P Lerner,
Yves Fradet,
Patrick J Bastian,
Armen Aprikian,
Pierre I Karakiewicz,
Hans Martin Fritsche,
Colin P N Dinney,
Derya Tilki,
Ashish M Kamat, Jonathan I Izawa,
Vincenzo Ficarra,
Yair Lotan,
Arthur I Sagalowsky,
Mark P Schoenberg,
Eila C Skinner
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ABSTRACT: OBJECTIVE: To validate the prognostic relevance of lymph node density (LND) and identify its optimal cut-points in a large international multicenter series of patients treated with radical cystectomy (RC) for invasive bladder cancer. METHODS: From 1993 to 2005, 4,430 bladder cancer patients who underwent RC without neoadjuvant chemotherapy were reviewed; of these, 1,038 were pN+M0 disease and form the basis of this report. RESULTS: Median age of patients was 67 years with median follow-up in survivors of 33 months. Overall, 5-year DSS estimate was 36%. Median number of lymph nodes removed was 18 (IQR, 11-32), median number of positive lymph nodes was 2 (IQR, 1-5), and median LND was 14.3% (IQR, 6.67-33.3%). LND as continuous variable was a stronger prognostic factor for DSS in patients that underwent a more extensive PLND (P < 0.001). HR for inverse association of LND with DSS increased incrementally with increasing LND cut-points. Categorizing LND into quintiles revealed strong tertiary distribution of risk based on LND <6%, 6%-41%, or >41% with cumulative 5-year DSS of 47%, 36%, and 21%, respectively (P < 0.001). When patients were stratified by adjuvant chemotherapy, LND remains independently prognostic in patients who received adjuvant chemotherapy as well as those who did not. CONCLUSION: Lymph node density is prognostic in bladder cancer patients who undergo a more extensive PLND and remains prognostic even when adjuvant chemotherapy is used. Prognostic value of LND is best represented as a continuum of risk and LND <6% represents the best possible outcome in patients with nodal disease.
Urologic Oncology 04/2011; · 3.22 Impact Factor
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Venu Chalasani,
Wassim Kassouf,
Joseph L Chin,
Yves Fradet,
Armen G Aprikian,
Adrian S Fairey,
Eric Estey,
Louis Lacombe,
Ricardo Rendon,
David Bell,
Ilias Cagiannos,
Darrell Drachenberg,
Jean-Baptiste Lattouf, Jonathan I Izawa
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ABSTRACT: Radical cystectomy may provide optimal survival outcomes in the management of clinical T1 bladder cancer. We present our data from a large, multi-institutional, contemporary Canadian series of patients who underwent radical cystectomy for clinical T1 bladder cancer in a single-payer health care system.
We collected a pooled database of 2287 patients who underwent radical cystectomy between 1993 and 2008 in 8 different centres across Canada; 306 of these patients had clinical T1 bladder cancer. Survival data were analyzed using Kaplan-Meier method and Cox regression analysis.
The median age of patients was 67 years with a mean follow-up time of 35 months. The 5-year overall, disease-specific and disease-free survival was 71%, 77% and 59%, respectively. The 10-year overall and disease-specific survival were 60% and 67%, respectively. Pathologic stage distribution was p0: 32 (11%), pT1: 78 (26%), pT2: 55 (19%), pT3: 60 (20%), pT4: 27 (9%), pTa: 16 (5%), pTis: 28 (10%), pN0: 215 (74%) and pN1-3: 78 (26%). Only 12% of patients were given adjuvant chemotherapy. On multivariate analysis, only margin status and pN stage were independently associated with overall, disease-specific and disease-free survival.
These results indicate that clinical T1 bladder cancer may be significantly understaged. Identifying factors associated with understaged and/or disease destined to progress (despite any prior intravesical or repeat transurethral therapies prior to radical cystectomy) will be critical to improve survival outcomes without over-treating clinical T1 disease that can be successfully managed with bladder preservation strategies.
Canadian Urological Association journal = Journal de l'Association des urologues du Canada 04/2011; 5(2):83-7. · 1.24 Impact Factor
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ABSTRACT: Surgical wait times have been shown to be of significance in other malignancies, but limited studies exist in renal cell cancer (RCC). We analyzed surgical waiting time for RCC patients to see if there was an adverse impact on pathological characteristics.
Our centre triages RCC patients on the basis of perceived tumour risk. The waiting time for surgery is adjusted stage for stage: clinical T1 at 90 days, T2 at 40 days, T3 and T4 at 30 days. We retrospectively reviewed the charts of 354 patients who underwent surgery for RCC. Patients were assessed for pathological upstaging, positive lymph nodes, tumour recurrence and tumour size within each stage. Analysis was performed, using surgical waiting time as a categorical variable, to test for associations with disease recurrence or adverse pathological characteristics.
The median time from the first consultation to surgery was 41 days and the mean follow-up was 26.6 months. Waiting time stage for stage was: clinical T1 at 57.12 days, clinical T2 at 36.8 days, clinical T3 and T4 at 30.32 days. On multivariate analysis, pathological tumour size was associated with progression, whereas no significant association was found between waiting time and upstaging. Higher stage tumours, sarcomatoid pathology and clinical evidence of progression were associated with shorter waiting times for early interventions.
There was no statistically significant evidence for upstaging or progression during the waiting period for our group of patients. The data reinforce previous studies reporting a "safe" period of active surveillance in T1 RCC without affecting their final pathological outcome.
Canadian Urological Association journal = Journal de l'Association des urologues du Canada 03/2011; 5(6):E148-51. · 1.24 Impact Factor
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ABSTRACT: We present the design, reliability, face, content and construct validity testing of a virtual reality simulator for transrectal ultrasound (TRUS), which allows doctors-in-training to perform multiple different biopsy schemes.
This biopsy system design uses a regular "end-firing" TRUS probe. Movements of the probe are tracked with a micro-magnetic sensor to dynamically slice through a phantom patient's 3D prostate volume to provide real-time continuous TRUS views. 3D TRUS scans during prostate biopsy clinics were recorded. Intrinsic reliability was assessed by comparing the left side of the prostate to the right side of the prostate for each biopsy. A content and face validity questionnaire was administered to 26 doctors to assess the simulator. Construct validity was assessed by comparing notes from experts and novices with regards to the time taken and the accuracy of each biopsy.
Imaging data from 50 patients were integrated into the simulator. The completed VR TRUS simulator uses real patient images, and is able to provide simulation for 50 cases, with a haptic interface that uses a standard TRUS probe and biopsy needle. Intrinsic reliability was successfully demonstrated by comparing results from the left and right sides of the prostate. Face and content validity respondents noted the realism of the simulator, and its appropriateness as a teaching model. The simulator was able to distinguish between experts and novices during construct validity testing.
A virtual reality TRUS simulator has successfully been created. It has promising face, content and construct validity results.
Canadian Urological Association journal = Journal de l'Association des urologues du Canada 02/2011; 5(1):19-26. · 1.24 Impact Factor
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Guru Sonpavde,
Myrna M Khan,
Seth P Lerner,
Robert S Svatek,
Giacomo Novara,
Pierre I Karakiewicz,
Eila Skinner,
Derya Tilki,
Wassim Kassouf,
Yves Fradet,
Colin P Dinney,
Hans-Martin Fritsche, Jonathan I Izawa,
Patrick J Bastian,
Vincenzo Ficarra,
Mark Schoenberg,
Arthur I Sagalowsky,
Yair Lotan,
Shahrokh F Shariat
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ABSTRACT: The conventional primary end point in trials of perioperative systemic therapy for muscle invasive bladder cancer is 5-year overall survival. We identified an association between disease-free survival at 2 to 3 years and 5-year overall survival.
We retrospectively analyzed a multicenter database containing records of 2,724 patients treated with radical cystectomy for muscle invasive bladder cancer with negative margins. Of these patients 844 had received adjuvant chemotherapy. We evaluated the association of disease-free survival at 2 and 3 years with overall survival at 5 years using Cox proportional hazards modeling and the kappa statistic.
Overall 2-year/3-year disease-free survival was 0.63/0.57 and 5-year overall survival was 0.47. The overall agreement between 2-year disease-free survival and 5-year overall survival was 79%, and between 3-year disease-free survival and 5-year overall survival was 81%. Agreements were similar when analyzed within pathological substages, radical cystectomy decades and adjuvant chemotherapy subgroups. The kappa statistic was 0.57 (95% CI 0.53-0.60) for 2-year disease-free survival/5-year overall survival and 0.61 (95% CI 0.58-0.64) for 3-year disease-free survival/5-year overall survival, indicating moderate agreement. The hazard ratio for disease-free survival as a time dependent variable was 12.7 (95% CI 11.60-13.90), indicating a strong relationship between disease-free and overall survival.
Disease-free survival rates at 2 and 3 years correlate with and are potential intermediate surrogates for 5-year overall survival in patients treated with radical cystectomy for muscle invasive bladder cancer regardless of adjuvant chemotherapy. These data warrant external validation and may expedite the development of adjuvant systemic therapy. In addition, they may be applicable to the neoadjuvant setting.
The Journal of urology 02/2011; 185(2):456-61. · 4.02 Impact Factor
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Guru Sonpavde,
Myrna M Khan,
Robert S Svatek,
Richard Lee,
Giacomo Novara,
Derya Tilki,
Seth P Lerner,
Gilad E Amiel,
Eila Skinner,
Pierre I Karakiewicz,
Patrick J Bastian,
Wassim Kassouf,
Hans-Martin Fritsche, Jonathan I Izawa,
Douglas S Scherr,
Vincenzo Ficarra,
Colin P Dinney,
Yair Lotan,
Yves Fradet,
Shahrokh F Shariat
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ABSTRACT: Patients with pathological T3N0 stage urothelial carcinoma of the bladder show a range of outcomes after radical cystectomy. Given that nomograms have included heterogeneous groups of patients, we focused on and stratified patients with pT3N0 urothelial carcinoma of the bladder after radical cystectomy into prognostically different risk groups to facilitate the development of adjuvant therapy trials for those at high risk.
The study comprised a total of 578 patients from 9 centers worldwide with pT3N0 urothelial carcinoma of the bladder who underwent radical cystectomy without perioperative chemotherapy. We evaluated the effect of pT3 substage at radical cystectomy, age, grade, lymphovascular invasion, margin status and number of lymph nodes removed on recurrence-free survival using Cox regression analysis. A weighted prognostic model was devised.
Median followup was 39.4 months (IQR 64). On multivariate analysis pT3 substage at radical cystectomy (pT3b vs pT3a HR 2.056, p <0.0001), lymphovascular invasion (positive vs negative HR 2.004, p <0.0001) and margin status (positive vs negative HR 2.503, p = 0.002) were associated with recurrence-free survival (concordance index 0.66) in the context of generally adequate lymph node dissection, that is with a median of 17 removed. Three risk groups were devised based on weighted variables with a 5-year recurrence-free survival rate of 79% (95% CI 70-84), 57% (95% CI 50-64) and 37% (95% CI 26-48) in the low, intermediate and high risk groups, respectively.
We constructed a user friendly prognostic risk model for patients with pT3N0 urothelial carcinoma of the bladder treated with radical cystectomy based on pT3 substage at radical cystectomy, lymphovascular invasion and margin status. These data warrant validation and may enable tailored monitoring and selection of appropriate patients for adjuvant therapy trials.
The Journal of urology 02/2011; 185(4):1216-21. · 4.02 Impact Factor
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Robert S Svatek,
Shahrokh F Shariat,
Giacomo Novara,
Eila C Skinner,
Yves Fradet,
Patrick J Bastian,
Ashish M Kamat,
Wassim Kassouf,
Pierre I Karakiewicz,
Hans-Martin Fritsche, Jonathan I Izawa,
Derya Tilki,
Vincenzo Ficarra,
Bjoern G Volkmer,
Hendrik Isbarn,
Colin P Dinney
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ABSTRACT: • To compare the clinical and pathologic stage among a large, multi-institutional series of patients undergoing radical and to determine the effect of stage discrepancy on outcomes.
• Data was collected from nine centers and 3,393 patients with urothelial carcinoma of the bladder (UCB) treated with radical cystectomy and pelvic lymphadenectomy without neo-adjuvant chemotherapy. • A retrospective cohort design was used to assess the percentage of patients experiencing stage discrepancy and the impact of stage discrepancy on time to disease relapse and time to death from UCB.
• Clinical under staging occurred in 50% of patients and pathologic down staging occurred in 18% of patients. • Up staging to muscle invasive disease occurred in 45.9% (n = 592) of 1,291 patients with clinical ≤T1, including 30.6% of patients with Tis only at transurethral resection. • Of the 3,166 patients with clinically organ confined (OC) tumor stage, 1,357 (42.9%) were up staged to non-organ confined pathologic tumor stage. • Within each clinical stage stratum, patients who were clinically under staged had a higher probability of disease relapse or death from UCB compared to those who were same staged or down staged on pathologic examination (P < 0.05).
• We identified clinical under staging in half of the patients undergoing radical cystectomy for UCB. • Up staging resulted in a higher likelihood of disease progression and eventual death from UCB. • These findings should be considered when utilizing pre-operative risk-adapted strategies for selecting candidates for neoadjuvant chemotherapy.
BJU International 01/2011; 107(6):898-904. · 2.84 Impact Factor
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Guru Sonpavde,
Myrna M Khan,
Robert S Svatek,
Richard Lee,
Giacomo Novara,
Derya Tilki,
Seth P Lerner,
Gilad E Amiel,
Eila Skinner,
Pierre I Karakiewicz,
Patrick J Bastian,
Wassim Kassouf,
Hans-Martin Fritsche, Jonathan I Izawa,
Vincenzo Ficarra,
Colin P Dinney,
Yair Lotan,
Yves Fradet,
Shahrokh F Shariat
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[hide abstract]
ABSTRACT: • To stratify risk of pathological (p) T2N0 urothelial carcinoma of the bladder after radical cystectomy (RC) based on pathological factors to facilitate the development of adjuvant therapy trials for high-risk patients.
• The study comprised 707 patients from a database of patients with pT2N0 urothelial carcinoma of the bladder who had undergone RC and not received perioperative chemotherapy. • The effect of residual pT-stage at RC, age, grade, lymphovascular invasion and number of lymph nodes removed on recurrence-free survival was evaluated using Cox regression analyses. A weighted prognostic model was devised with significant variables.
• The median follow up was 60.9 months. In multivariable analyses, residual disease at RC (pT2a: hazard ratio (HR) 1.740, P = 0.03; for pT2b: HR 3.075, P < 0.001; both compared with <pT2), high-grade (HR 2.127, P = 0.09) and lymphovascular invasion (HR 2.234, P < 0.001) were associated with recurrence-free survival (c = 0.70). • Three risk groups were devised based on weighted variables with 5-year recurrence-free survival of 95% (95% CI 87-98), 86% (95% CI 81-90) and 62% (95% CI 54-69) in the good-risk, intermediate-risk and poor-risk groups, respectively (c = 0.68). The primary limitation is the retrospective and multicenter feature.
• A prognostic risk model for patients with pT2N0 bladder cancer undergoing RC with generally adequate lymph node dissection was constructed based on residual pathological stage at RC, grade and lymphovascular invasion. • These data warrant validation and may enable the selection of patients with high-risk pT2N0 urothelial carcinoma of the bladder for adjuvant therapy trials.
BJU International 11/2010; 108(5):687-92. · 2.84 Impact Factor
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ABSTRACT: Carcinoma cuniculatum of the penis is an extremely rare variant of squamous cell carcinoma characterized by an endophytic deeply branching and burrowing growth pattern. One documented case series demonstrated afflicted patients ranging in age from 73-83 years with the tumour located on the glans penis, coronal sulcus or foreskin. We report a case of a 55-year-old with disease located on the ventral aspect of the shaft of the penis. The tumour was invasive into the deep dermal connective tissue, comparatively superficial to all previous documented cases. He subsequently underwent a partial penectomy. The case is discussed with a brief review of the literature.
Canadian Urological Association journal = Journal de l'Association des urologues du Canada 10/2010; 4(5):E129-32. · 1.24 Impact Factor
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Robert S Svatek,
Shahrokh F Shariat,
Robert E Lasky,
Eila C Skinner,
Giacomo Novara,
Seth P Lerner,
Yves Fradet,
Patrick J Bastian,
Wassim Kassouf,
Pierre I Karakiewicz,
Hans-Martin Fritsche,
Stefan C Müller, Jonathan I Izawa,
Vincenzo Ficarra,
Arthur I Sagalowsky,
Mark P Schoenberg,
Arlene O Siefker-Radtke,
Randall E Millikan,
Colin P N Dinney
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ABSTRACT: The role of adjuvant chemotherapy for patients with high-risk urothelial carcinoma of the bladder (UCB) is not well defined. Here we address the value of adjuvant chemotherapy in patients undergoing radical cystectomy for UCB in an off-protocol routine clinical setting.
We collected and analyzed data from 11 centers contributing retrospective cohorts of patients with UCB treated with radical cystectomy without neoadjuvant chemotherapy. Patients were grouped into quintiles based on their risk of disease progression using estimates from a fitted multivariable Cox proportional hazards model. The association of adjuvant chemotherapy with survival was explored across separate quintiles.
The cohort consisted of 3,947 patients, 932 (23.6%) of whom received adjuvant chemotherapy. Adjuvant chemotherapy was independently associated with improved survival (hazard ratio, 0.83; 95% confidence interval, 0.72-0.97%, P = 0.017). However, the effect of adjuvant chemotherapy was significantly modified by the individual's risk of disease progression such that an increasing benefit from adjuvant chemotherapy was seen across higher-risk subgroups (P < 0.001). There was a significant improvement in survival between the treated and nontreated patients in the highest-risk quintile (hazard ratio, 0.75; 95% confidence interval, 0.62-0.90; P = 0.002). This group was characterized by an estimated 32.8% 5-year probability of cancer-specific survival, with 86.6% of patients having both advanced pathologic stage (> or =T(3)) and nodal involvement.
Adjuvant chemotherapy is associated with a significant improvement in survival for patients treated in an off-protocol clinical setting. Selective administration in patients at the highest risk for disease progression, such as those with advanced pathologic stage and nodal involvement, may optimize the therapeutic benefit of adjuvant chemotherapy.
Clinical Cancer Research 09/2010; 16(17):4461-7. · 7.74 Impact Factor
