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ABSTRACT: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Micropapillary bladder cancer is a high grade variant with poor prognosis. There is no consensus about patients with micropapillary bladder cancer receiving neoadjuvant chemotherapy, but many suggest that radical cystectomy should not be delayed. Data from this study suggest that patients with micropapillary bladder cancer have a similar rate of response to neoadjuvant chemotherapy to that of patients with urothelial carcinoma. If these patients have pT0 disease, their survival is significantly improved at 2 years. OBJECTIVE: To describe the pathological outcomes of patients with muscle-invasive micropapillary bladder cancer who have undergone neoadjuvant chemotherapy. PATIENTS AND METHODS: A total of 82 patients with muscle-invasive micropapillary bladder cancer were treated between 1997 and 2010. After excluding those with metastatic disease, micropapillary histology only at radical cystectomy (RC), and chemo-radiation as primary treatment, 44 patients remained. All patients had ≥cT2 disease before chemotherapy/surgery. The median follow-up after RC was 28 months. Neoadjuvant chemotherapy was initiated in 29 (66%) patients and all patients underwent RC (93%) or partial cystectomy (7%). RESULTS: Micropapillary histology was diagnosed at first transurethral resection in 37 (84%) patients. Final RC pathology revealed pT0 in 15 (34%) patients and positive lymph nodes in 13 (31%) patients. Down-staging to pT0 occurred in 13 (45%) of those who received neoadjuvant chemotherapy compared with two (13%) of those who did not (P = 0.049). Patients with pT0 disease with micropapillary histology had higher overall survival rates (25 vs. 92%) and lower rates of bladder cancer recurrence (21 vs. 79%) at the 24-month follow-up. CONCLUSIONS: Almost half of the patients responded completely to neoadjuvant chemotherapy with a pT0 rate of 45%; therefore, patients with the micropapillary variant of urothelial carcinoma should not be excluded from consideration for neoadjuvant chemotherapy.
BJU International 02/2013; · 2.84 Impact Factor
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ABSTRACT: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Intravesical bacille Calmette-Guérin (BCG) is generally considered to be contraindicated in immunologically compromised patients with bladder cancer because it may be ineffective and potentially toxic. Therefore, there is little experience with BCG in individuals with impaired immune systems. The present study provides evidence that intravesical BCG is safe and effective in the short term against non-muscle-invasive bladder cancer affecting patients who were receiving immunosuppressive medications. This included anti-rejection drugs to support a solid organ transplant, high-dose steroids for autoimmune inflammatory diseases, and the first description of BCG use in patients who were receiving concomitant systemic chemotherapy for unrelated malignant neoplasms. OBJECTIVE: To investigate the outcomes of bacille Calmette-Guérin (BCG) therapy in patients with bladder cancer who were immunologically compromised. PATIENTS AND METHODS: In all, 45 immunosuppressed patients with high-grade non-muscle-invasive bladder cancer received BCG therapy. Twelve had functioning organ transplants, 23 were undergoing systemic chemotherapy for unrelated cancers, and 10 were taking steroids for autoimmune or related diseases. Patients received a 6-week induction course of BCG therapy. Relapsing patients were eligible for retreatment. All patients were followed for median (range) of 40 (12-72) months. End points were response to BCG and 5-year recurrence-free, progression-free and overall survival rates. RESULTS: In all, nine of the 12 transplant patients responded completely to one or two cycles of BCG compared with 99% (32/33) of other immunosuppressed patients. Half the patients with unrelated cancers and autoimmune diseases recurred vs all but one of the transplant patients (P = 0.008). Of the 12 transplant patients, six of 12 progressed vs five of 33 (15%) of the other patient groups (P = 0.02). Five patients died (11%), two of bladder cancer (both in transplant patients), and three of unrelated causes. BCG was well tolerated. None of the patients developed bacterial or BCG sepsis. Although this is largest series evaluating BCG in transplant and other immune-suppressed patients, it represents few patients and results must be interpreted with caution. CONCLUSIONS: We conclude that intravesical BCG is safe and effective in immunologically compromised patients with bladder cancer. Transplant patients fare worse and should be considered for early cystectomy if they fail BCG therapy.
BJU International 01/2013; · 2.84 Impact Factor
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ABSTRACT: OBJECTIVE: To review our experience managing bladder cancer (BCa) in patients who have had renal transplantation. Optimal oncologic treatment can be challenging due to the immunosuppressed state and higher comorbidity. METHODS: From January 2000 to August 2011, we identified 17 patients with a history of renal transplantation who were treated for BCa. Clinical, demographic, and oncologic data were collected. Patients treated with intravesical bacillus Calmette-Guérin (BCG) were assessed for complications. RESULTS: BCa diagnosis occurred at a median of 88.1 months after renal transplantation. Median age was 62.4 years and median follow-up was 9.2 months. The most common presentation was gross hematuria (58.8%), and the median Charlson comorbidity index was 5. Twelve patients were identified with non-muscle invasive (NMI) BCa. Four patients with NMI BCa received intravesical BCG, with no urinary tract infection, fever, or BCG-associated sepsis. Four patients were identified with muscle-invasive bladder cancer (MIBC), and 1 patient had biopsy proven metastatic disease. Five patients underwent radical cystectomy (RC) with diversion, 7 underwent transurethral resection and surveillance, 3 underwent chemotherapy, and 1 received palliative radiation for metastatic disease. Overall, 6 patients were deceased, 4 of whom died of disease at a median of 9.7 months from the time of BCa diagnosis. CONCLUSION: Treatment of patients with BCa after renal transplantation is challenging because of immunosuppression and overall high comorbidity. Optimal management with stage-appropriate therapy should be considered in appropriate patients. Intravesical BCG may be considered in select patients, although overall efficacy may be reduced.
Urology 01/2013; · 2.43 Impact Factor
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ABSTRACT: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Bladder cancer patients with lamina propria invasion (T1 disease) and residual T1 disease on restaging transurethral resection of bladder tumour (re-TURBT) are at a very high risk for recurrence and progression. Despite this risk, most patients are treated with a bladder preserving approach and not immediate radical cystectomy (RC). In this study we have shown that a quarter of patients with T1 bladder cancer and residual T1 on re-TURBT who are treated with immediate RC are found to have carcinoma invading bladder muscle at RC and 5% have lymph node metastases. We have also found that >30% of patients treated with deferred RC after initial bladder-preserving therapy harbour carcinoma invading bladder muscle and almost 20% of these patients have lymph node metastases. Thus, immediate RC should be considered in all patients with T1 bladder cancer and residual T1 on re-TURBT. OBJECTIVE: To report the overall survival (OS) and cancer-specific survival (CSS) of patients with residual T1 bladder cancer on restaging transurethral resection of the bladder tumour (re-TURBT). MATERIALS AND METHODS: We performed a retrospective review of 150 evaluable patients treated for T1 bladder cancer with residual T1 disease found on re-TURBT between 1990 and 2007. Patients were treated with immediate radical cystectomy (RC) or a bladder-preserving approach (deferred or no RC). A univariate Cox proportional hazards regression model was used to test the association between treatment approach and survival. RESULTS: Residual T1 bladder cancer was found in 150 evaluable patients, of whom 57 received immediate RC and 93 were treated with a bladder-preserving approach. Fourteen out of 57 patients receiving immediate RC and 8/26 patients receiving deferred RC had carcinoma invading bladder muscle in the RC specimen. Three out of 57 and 5/26 patients had lymph node metastases in the RC specimen. Median follow-up was 3.74 years. Thirty-nine patients died during follow-up, 16 from bladder cancer. There was no significant association between immediate RC and CSS (hazard ratio [HR] 1.15, 95% confidence interval [CI] 0.43-3.09, P = 0.8) or OS (HR 0.79, 95% CI 0.4-1.53, P = 0.5). CONCLUSIONS: Because of the low number of events we cannot conclude whether RC offers a survival advantage in patients with residual T1 bladder cancer on re-TURBT. Since a quarter of patients had carcinoma invading bladder muscle, RC should be considered in these patients. A larger, preferably randomized, study with longer follow-up is needed.
BJU International 11/2012; · 2.84 Impact Factor
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ABSTRACT: PURPOSE: Urachal carcinomas are rare urologic neoplasms that arise along the urachal remnant from the umbilicus to the dome of the bladder. No published study has examined the diagnostic accuracy of modern preoperative testing to differentiate urachal carcinoma from a benign urachal cyst and spare resection of potentially benign urachal tissue. Our objective was to determine if a urachal mass can be safely diagnosed preoperatively. MATERIALS AND METHODS: 104 patients with a urachal mass treated between 1979 and 2011. Exclusion criteria were unresectable metastatic disease at presentation, patients that did not undergo surgery, and management by transurethral resection alone. Of the patients that remained, only 65 had both preoperative diagnostic testing and definitive pathologic results available for analysis. Mean age was 51 years, 86% were Caucasian and 65% were male. Accuracy of diagnosis based on preoperative tests was compared to final pathology (cancer or benign). RESULTS: Fifty-seven tumors (87%) were malignant and the majority of masses (83%) were adenocarcinoma. Compared to computed tomography, cytology, and exploration under anesthesia, transurethral resection of the bladder tumor has the highest sensitivity (0.93), specificity (1), and positive predictive value (1), but a low negative predictive value (0.5). Limitations included small cohort size and few benign urachal masses for comparison. CONCLUSIONS: No test has a high enough negative predictive value to prevent excision of a urachal mass. With few treatment options for localized, advanced, and metastatic urachal cancer, these data suggest that early excision remains the best treatment for a suspicious urachal mass.
The Journal of urology 10/2012; · 4.02 Impact Factor
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ABSTRACT: PURPOSE: To investigate trends in urinary diversion usage and surgeon characteristics in the utilization of incontinent and continent urinary diversions using data from American Board of Urology. METHODS: Annualized case log data for urinary diversions were obtained from the American Board of Urology for urologists certifying or recertifying, from 2002 to 2010. We evaluated the association between surgeon characteristics and the use of any urinary diversion or the type of urinary diversion. RESULTS: Of 5,096 certifying or recertifying urologist case logs examined, 37% (n=1,868) performed any urinary diversions. The median number was 4 per year (IQR 2-6),4% (n=222) performed =10 per year. On multivariable analysis, younger urologists, those self-identified as oncologists or female urologists, certifying in more recent years, in larger practice areas, or outside of the Northeast region of the United States were more likely to perform any urinary diversions. Only 9% (n=471) of the total cohort performed any continent urinary diversions. The likelihood of performing any continent urinary diversions increased with the number of urinary diversions (p <0.0001), and as the volume of urinary diversions increased, the proportion of these made up by continent urinary diversions also increased (p <0.0005). Surgeons in private practice settings or located in the Northeast were less likely to perform continent urinary diversions. CONCLUSION: A minority of urologists performs any urinary diversions, and continent urinary diversions are most frequently performed by high volume surgeons. The type of urinary diversion a patient receives may depend, in part, on the characteristics of their surgeon.
The Journal of urology 09/2012; · 4.02 Impact Factor
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ABSTRACT: Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Cigarette smoking is the leading cause of urothelial carcinoma; however, the impact of smoking on outcomes after surgery for upper tract urothelial carcinoma is unknown. One study suggests that patients with a smoking history have an increased risk of recurrence in the bladder compared with never smokers but these patients did not differ with respect to time to pelvic recurrence or distant metastasis. We subdivided smokers into current and former smokers and performed multivariate analyses that showed that smoking status was not an independent predictor of recurrence when traditional prognostic factors were taken into account. In addition, competing risks analyses showed that although current smoking did not increase the risk of recurrence, it imparted a significant risk of dying compared with former and never smoking. OBJECTIVE: • To evaluate the impact of smoking exposure on oncological outcomes in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). MATERIALS AND METHODS: • Patient and disease characteristics from 288 patients with UTUC treated with RNU between 1995 and 2008 were collected from a prospectively maintained database at the Memorial Sloan-Kettering Cancer Center. • Disease recurrence was defined as distant metastases, or local failure in the operative site or regional nodes. • Factors associated with recurrence and death were determined. RESULTS: • The prevalence of current, former and never smoking at diagnosis was 19.1%, 55.2%, and 25.7%, respectively. • 71.0% of patients reported a ≥20 pack-year smoking history. • With a median follow-up of 4.02 years, disease recurrence occurred in 27% (n= 79) of patients and 41% (n= 117) died during follow-up. • While age at diagnosis, American Society of Anesthesiologists score, advanced stage, nodal involvement and high grade adversely affected recurrence-free survival, smoking status was not associated with risk of recurrence or death in multivariate analysis (P= 0.60). • Multivariate competing risks regression showed that current smokers faced a significantly higher risk of death than never smokers (hazard ratio 3.64, 95% confidence interval 1.59-8.34). CONCLUSIONS: • While smoking status at diagnosis and cumulative smoking exposure were not associated with UTUC recurrence, our findings highlight the substantial risk of death in patients with UTUC who are active smokers. • Treatment plans to promote smoking cessation are recommended for these patients.
BJU International 05/2012; · 2.84 Impact Factor
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ABSTRACT: The extent of lymphadenectomy needed to optimize oncologic outcomes after radical cystectomy (RC) for patients with regionally advanced bladder cancer (BCa) is unclear.
Evaluate the effect of the location of lymph node metastasis on recurrence-free survival (RFS) and cancer-specific survival (CSS) for patients undergoing RC with a mapping pelvic lymph node dissection (PLND).
A study of 591 patients undergoing RC with mapping PLND was completed between 2000 and 2010. Median follow-up was 30 mo.
RC with mapping PLND.
We evaluated the impact of lymph node involvement by location on disease outcomes using the 2010 TNM staging system. Survival estimates were described using Kaplan-Meier methods. Gender, age, pathologic stage, histology, number of positive nodes, location of positive nodes, node density, use of perioperative chemotherapy, and grade were evaluated as predictors of RFS and CSS using multivariate Cox proportional hazard regression.
Overall, 114 patients (19%) had lymph node involvement, and 42 patients (7%) had pN3 disease. On multivariate analysis, the number of positive lymph nodes (one or two or more) was significantly associated with increased risk of cancer-specific death (hazard ratio [HR]: 1.9 [95% confidence interval (CI), 1.04-3.46], p=0.036; versus HR: 4.3 [95% CI, 2.25-8.34], p<0.0005). Positive lymph node location was not an independent predictor of RFS or CSS. Five-year RFS for pN3 patients undergoing RC with PLND was 25% (95% CI, 10-42). This finding was not statistically different from our pN1 and pN2 patients (38% [95% CI, 22-54] and 35% [95% CI, 11-60], respectively). This study is limited by the lack of prospective randomization and a control group.
The outcome for patients with involved common iliac lymph nodes was similar to the outcome for patients with primary nodal basin disease. These data support inclusion of the common iliac lymph nodes (pN3) in the nodal staging system for BCa. Lymph node location was not an independent predictor of outcome, whereas the number of positive lymph nodes was an independent predictor of worse oncologic outcome (pN1, pN2). Further refinements of the TNM system to provide improved prognostication are warranted.
European urology 02/2012; 61(5):1025-30. · 7.67 Impact Factor
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ABSTRACT: We compared renal function and oncologic outcomes of parenchymal sparing ureteral resection with radical nephroureterectomy for the treatment of upper tract urothelial carcinoma confined to the ureter.
Review of a large institutional database identified 367 patients treated for primary upper tract urothelial carcinoma with radical nephroureterectomy or parenchymal sparing ureteral resection from 1994 to 2009. Patients with known renal pelvis tumors, muscle invasive urothelial carcinoma, prior cystectomy, contralateral upper tract urothelial carcinoma, metastatic disease or chemotherapy were excluded, leaving 120 patients for analysis. Estimated glomerular filtration rate was calculated using the Modification of Diet in Renal Disease equation. Recurrence-free, cancer specific and overall survival were estimated using Kaplan-Meier analysis.
Radical nephroureterectomy was performed in 87 patients and parenchymal sparing ureteral resection in 33. Median age at surgery was 73 years in the radical nephroureterectomy group (IQR 64-76) vs 70 years (IQR 59-77) in the parenchymal sparing ureteral resection group (p = 0.5). The radical nephroureterectomy and parenchymal sparing ureteral resection cohorts had several disparate clinicopathological variables including preoperative hydronephrosis (80% vs 45%, p = 0.0006), stage (pT3 or greater 26% vs 9%, p = 0.01) and baseline estimated glomerular filtration rate (51 vs 63 ml/minute/1.73 m(2), p = 0.009). Patients who underwent radical nephroureterectomy experienced a significantly greater decrease in estimated glomerular filtration rate after surgery (median -7 vs 0 ml/minute/1.73 m(2), p <0.001). Median followup was 4.2 years. Of the patients 79 experienced cancer recurrence and 44 died (28 of upper tract urothelial carcinoma). There were no obvious differences in the rates of recurrence, cancer specific death or overall death by procedure type. However, due to the limited number of events we cannot exclude the possibility that there are large differences in oncologic outcomes by procedure type.
Parenchymal sparing ureteral resection is associated with superior postoperative renal function. However, the impact on cancer control cannot be determined conclusively due to the small sample size and putative selection bias.
The Journal of urology 12/2011; 187(2):429-34. · 4.02 Impact Factor
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ABSTRACT: Indications for partial nephrectomy (PN) in the treatment of renal cell carcinoma are evolving, particularly for larger, more complex tumors.
Compare single-institution outcomes for minimally invasive partial nephrectomy (MIPN) and open partial nephrectomy (OPN) for tumors>4-7 cm.
A total of 2290 patients underwent PN from 2002 to 2010 at Memorial Sloan-Kettering Cancer Center; 280 had >4-7 cm renal cortical tumors. Of these 280 patients, 230 had pT1b, 48 had pT3a, and 2 had angiomyolipomas; 226 underwent OPN and 54 underwent MIPN (16 robot-assisted and 37 laparoscopic procedures). Perioperative management was uniform on the clinical pathway. Perioperative data, clinicopathologic variables, complications within 30 d, and oncologic outcomes were reviewed.
Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Complications were reported from prospectively collected data based on a modified Clavien system. The Fisher exact and Mann-Whitney U tests were used for descriptive statistical analysis. Kaplan-Meier methods were used to estimate survival.
Median follow-up for OPN and MIPN was 29 and 13 mo, respectively. There were no statistically significant differences in age, gender, preoperative American Society of Anesthesiologists score, laterality, histologic subtype, tumor size, tumor stage, or margin status between procedures. Univariate analysis revealed significantly greater values in the OPN group for preoperative eGFR, renal artery clamp time, estimated blood loss, use of renal hypothermia, and length of stay. Differences in overall survival and recurrence-free survival were not statistically significant; however, short median follow-up times limit comparison. There was no significant difference in the number of complications grade≥3 (p=0.1) or urine leaks requiring intervention (p=0.7). Limitations include the retrospective nature of the study and the possibility of selection bias.
OPN and MIPN procedures performed in patients with tumors>4-7 cm offer acceptable and comparable results in terms of operative, functional, and convalescence measures, regardless of approach.
European urology 12/2011; 61(3):593-9. · 7.67 Impact Factor
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ABSTRACT: Bacillus Calmette-Guérin (BCG) is the standard intravesical treatment of high-risk noninvasive (Ta, T1, Tis) bladder cancer. Maintenance BCG is recommended for maximum efficacy.
We compared our results in a large cohort of high-risk bladder cancer patients who received BCG without maintenance with published results from randomized maintenance BCG trials.
A cohort of 1021 patients underwent restaging transurethral resection for high-risk (Ta, T1, Tis) bladder cancer.
Patients received a 6-wk induction course of BCG therapy. Responding patients did not receive maintenance BCG. Relapsing patients were eligible for retreatment with BCG. All patients were followed for a minimum of 5 yr.
End points were 5-yr tumor- and progression-free survival rates.
Of 816 complete responders to induction BCG, 2- and 5-yr recurrence-free survival rates were 73% and 46%, respectively. The progression-free survival rate was 89%. Progression-free survival time was 56 mo (95% confidence interval, 55-58 mo). Thirty-two percent of the patients required another course of BCG therapy. We cannot exclude that maintenance BCG may benefit patients beyond 5 yr over induction BCG alone and selective BCG retreatments.
Our results with BCG treatment without maintenance of patients with high-risk non-muscle-invasive bladder cancer compare favorably with trials in which comparable patients received maintenance BCG.
European urology 07/2011; 60(1):32-6. · 7.67 Impact Factor
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ABSTRACT: To create a preoperative multivariable model to identify patients at risk of muscle-invasive (pT2+) upper tract urothelial carcinoma (UTUC) and/or non-organ confined (pT3+ or N+) UTUC (NOC-UTUC) who potentially could benefit from radical nephroureterectomy (RNU), neoadjuvant chemotherapy and/or an extended lymph node dissection.
We retrospectively analysed data from 324 consecutive patients treated with RNU between 1995 and 2008 at a tertiary cancer centre. Patients with muscle-invasive bladder cancer were excluded, resulting in 274 patients for analysis. Logistic regression models were used to predict pT2+ and NOC-UTUC. Pre-specified predictors included local invasion (i.e. parenchymal, renal sinus fat, or periureteric) on imaging, hydronephrosis on imaging, high-grade tumours on ureteroscopy, and tumour location on ureteroscopy. Predictive accuracy was measured by the area under the curve (AUC).
The median follow-up for patients without disease recurrence or death was 4.2 years. Overall, 49% of the patients had pT2+, and 30% had NOC-UTUC at the time of RNU. In the multivariable analysis, only local invasion on imaging and ureteroscopy high grade were significantly associated with pathological stage. AUC to predict pT2+ and NOC-UTUC were 0.71 and 0.70, respectively.
We designed a preoperative prediction model for pT2+ and NOC-UTUC, based on readily available imaging and ureteroscopic grade. Further research is needed to determine whether use of this prediction model to select patients for conservative management vs RNU, neoadjuvant chemotherapy, and/or extended lymphadenectomy will improve patient outcomes.
BJU International 06/2011; 109(1):77-82. · 2.84 Impact Factor
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ABSTRACT: The types of surveillance recommended after radical cystectomy and the degree of patient compliance are not well characterized. We identified the pattern of post-cystectomy surveillance recommended in the oncologic community and assessed compliance to a predetermined schedule among a small group of urologists.
A survey was sent inquiring about the number of patients followed after cystectomy, physician specialty, type of practice, whether the followup schedule was stage dependent, the frequency of office visits and the type of tests. To assess noncompliance to a strict followup schedule we analyzed the records of 647 patients who underwent radical cystectomy.
The overall response rate to the survey was 37% (123 of 330). Of the respondents 96% were urologists, with 72% from United States academic centers, 13% from non-United States academic centers and 14% in private practice. In addition, 21% reported following yearly more than 100 patients after cystectomy, 29% between 51 and 100 patients, and 43% between 1 and 50. Of the respondents 60% tailored the followup schedule based on pathological stage. Computerized tomography of the abdomen and pelvis, chest x-ray and urine cytology were the most frequent tests used. Computerized tomography of the chest, magnetic resonance imaging and abdominal ultrasound were used occasionally.
There was significant deviation from a predetermined followup schedule. There was no uniformity among urological oncologists in post-cystectomy surveillance and there was lack of compliance to a predetermined followup schedule.
The Journal of urology 06/2011; 185(6):2091-6. · 4.02 Impact Factor
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Hikmat A Al-Ahmadie,
Gopa Iyer,
Manickam Janakiraman,
Oscar Lin,
Adriana Heguy,
Satish K Tickoo,
Samson W Fine,
Anuradha Gopalan,
Ying-bei Chen,
Arjun Balar,
Jamie Riches,
Bernard Bochner, Guido Dalbagni,
Dean F Bajorin,
Victor E Reuter,
Matthew I Milowsky,
David B Solit
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ABSTRACT: FGFR3 mutations are common in low-grade urothelial carcinoma and represent a potential therapeutic target in this disease. Their incidence and functional role in high-grade urothelial carcinoma (HGUC), which displays an increased propensity for recurrence and muscularis propria invasion, is less well defined. We developed a mass spectrometry-based genotyping assay to define the incidence of FGFR3 mutations in a large clinically annotated set of urothelial carcinomas. FGFR3 mutations were found in 17% of HGUC versus 84% of low-grade lesions. Retrospective pathological review of the class of FGFR3 mutant HGUC revealed unique histological features, characterized by a bulky, exophytic component with branching papillary architecture as well as irregular nuclei with a koilocytoid appearance. The predictive value of this histological appearance was confirmed using a prospective set of 49 additional HGUCs. Prospective histological review was able to correctly predict for the presence of an FGFR3 mutation in 13/24 HGUC specimens that exhibited the distinct morphology (54%). All 25 specimens lacking the defined histological features were FGFR3 wild-type for a negative predictive value of 100%. Macrodissection of individual tumours confirmed the presence of the FGFR3 mutant allele in non-invasive and invasive, low and high-grade regions of individual tumours and in the lymph node metastases of patients whose tumours possessed the characteristic morphological signature, suggesting that FGFR3 mutations are not restricted to the more clinically indolent regions of HGUCs. These data suggest that histological screening of HGUCs followed by confirmatory genotyping can be used to enrich for the population of HGUCs most likely to harbour activating mutations in the FGFR-3 receptor tyrosine kinase. Histological review could thus aid in the development of targeted inhibitors of FGFR-3 by facilitating the identification of the subset of patients most likely to harbour activating mutations in the FGFR3 gene.
The Journal of Pathology 06/2011; 224(2):270-9. · 6.32 Impact Factor
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ABSTRACT: To investigate the utility of (11)C-acetate positron emission tomography/computed tomography (PET/CT) for staging of bladder cancer and response assessment after neoadjuvant chemotherapy.
Seventeen patients underwent (11)C-acetate PET/CT ≤1 month before radical cystectomy (RC) and pelvic lymph node dissection (PLND). Ten patients had undergone neoadjuvant chemotherapy prior to PET. Histopathology from RC and PLND (n = 16) or nodal biopsy (n = 1) served as gold standard.
Eight of 10 residual tumors showed abnormal (11)C-acetate uptake; two cases of residual TiS were false negative, three cases were false positive, and three true negative. Three patients showed true positive uptake in LN. False positive uptake occurred in 14 LN regions secondary to granulomatous disease after prior intravesical Bacillus Calmette-Guerin (BCG) therapy.
(11)C-acetate has good sensitivity for bladder cancer and LN metastases. However, false positive uptake due to inflammation or granulomatous infection can occur, limiting the staging utility of (11)C-acetate after prior intravesical BCG therapy.
Molecular imaging and biology: MIB: the official publication of the Academy of Molecular Imaging 04/2011; 14(2):245-51. · 2.47 Impact Factor
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ABSTRACT: •To evaluate the effect of preoperative cisplatin-based chemotherapy on the regional lymph nodes of patients with bladder cancer who attain pathological T0 status in the bladder after chemotherapy followed by radical cystectomy.
•Patients who underwent radical cystectomy at MSKCC for urothelial carcinoma of the bladder were retrospectively reviewed. •Those patients achieving pT0 status after preoperative chemotherapy were identified and classified into two groups, those rendered pT0: (i) after receiving neoadjuvant chemotherapy and (ii) after receiving definitive chemotherapy (defined in this case as chemotherapy given for unresectable or regionally metastatic disease). •These two groups were analyzed separately for lymph node status at cystectomy and regional lymph node recurrence.
•Of 169 pT0 patients, 24 patients (14%) had received neoadjuvant chemotherapy, whereas 17 patients (10%) had received definitive chemotherapy for unresectable or regionally metastatic disease. •No patient rendered pT0 after neoadjuvant chemotherapy had lymph node involvement at radical cystectomy or recurrence within the regional lymph node template. •Among patients with advanced disease rendered pT0 by definitive chemotherapy, 35% had lymph node involvement at radical cystectomy or subsequent recurrence within the dissection template.
•Patients achieving pT0 status after receiving neoadjuvant chemotherapy had no evidence of lymph node involvement at cystectomy. •Patients undergoing definitive chemotherapy for advanced disease followed by cystectomy experienced reduced rates of nodal involvement compared to the lymph node-positive rates predicted by preoperative clinical staging. However, there remains a risk of regional lymph node involvement in this group.
BJU International 02/2011; 108(8 Pt 2):E272-7. · 2.84 Impact Factor
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ABSTRACT: Over the past two decades, there has been an increasing focus on quality of life outcomes in urological diseases. Patient-reported outcomes research has relied on structured assessments that constrain interpretation of the impact of disease and treatments. In this study, we present content analysis and psychometric evaluation of the Quality of Life Appraisal Profile. Our evaluation of this measure is a prelude to a prospective comparison of quality of life outcomes of reconstructive procedures after cystectomy.
Fifty patients with bladder cancer were interviewed prior to surgery using the Quality of Life Appraisal Profile. Patients also completed the EORTC QLQ-C30 and demographics. Analysis included content coding of personal goal statements generated by the Appraisal Profile, examination of the relationship of goal attainment to content, and association of goal-based measures with QLQ-C30 scales.
Patients reported an average of 10 personal goals, reflecting motivational themes of achievement, problem solving, avoidance of problems, maintaining desired circumstances, letting go of roles and responsibilities, acceptance of undesirable situations, and attaining milestones. 503 goal statements were coded using 40 different content categories. Progress toward goal attainment was positively correlated with relationships and activities goals, but negatively correlated with health concerns. Associations among goal measures provided evidence for construct validity. Goal content also differed according to age, gender, employment, and marital status, lending further support for construct validity. QLQ-C30 functioning and symptom scales were correlated with goal content, but not with progress toward goal attainment, suggesting that patients may calibrate progress ratings relative to their specific goals. Alternately, progress may reflect a unique aspect of quality of life untapped by more standard scales.
The Brief Quality of Life Appraisal Profile was associated with measures of motivation, goal content and progress, as well as relationships with demographic and standard quality of life measures. This measure identifies novel concerns and issues in treating patients with bladder cancer, necessary for a more comprehensive evaluations of their health-related quality of life.
Health and Quality of Life Outcomes 02/2011; 9:10. · 2.11 Impact Factor
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ABSTRACT: Open radical nephroureterectomy (ORN) is the current standard of care for upper tract urothelial carcinoma (UTUC), but laparoscopic radical nephroureterectomy (LRN) is emerging as a minimally invasive alternative. Questions remain regarding the oncologic safety of LRN and its relative equivalence to ORN.
Our aim was to compare recurrence-free and disease-specific survival between ORN and LRN.
We retrospectively analyzed data from 324 consecutive patients treated with radical nephroureterectomy (RN) between 1995 and 2008 at a major cancer center. Patients with previous invasive bladder cancer or contralateral UTUC were excluded. Descriptive data are provided for 112 patients who underwent ORN from 1995 to 2001 (pre-LRN era). Comparative analyses were restricted to patients who underwent ORN (n=109) or LRN (n=53) from 2002 to 2008. Median follow-up for patients without disease recurrence was 23 mo.
All patients underwent RN.
Recurrence was categorized as bladder-only recurrence or any recurrence (bladder, contralateral kidney, operative site, regional lymph nodes, or distant metastasis). Recurrence-free probabilities were estimated using Kaplan-Meier methods. A multivariable Cox model was used to evaluate the association between surgical approach and disease recurrence. The probability of disease-specific death was estimated using the cumulative incidence function.
Clinical and pathologic characteristics were similar for all patients. The recurrence-free probabilities were similar between ORN and LRN (2-yr estimates: 38% and 42%, respectively; p=0.9 by log-rank test). On multivariable analysis, the surgical approach was not significantly associated with disease recurrence (hazard ratio [HR]: 0.88 for LRN vs ORN; 95% confidence interval [CI], 0.57-1.38; p=0.6). There was no significant difference in bladder-only recurrence (HR: 0.78 for LRN vs ORN; 95% CI, 0.46-1.34; p=0.4) or disease-specific mortality (p=0.9). This study is limited by its retrospective nature.
Based on the results of this retrospective study, no evidence indicates that oncologic control is compromised for patients treated with LRN in comparison with ORN.
European urology 11/2010; 58(5):645-51. · 7.67 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: The prognostic impact of primary tumor location on outcomes for patients with upper-tract urothelial carcinoma (UTUC) is still contentious.
To test the association between tumor location and disease recurrence and cancer-specific survival (CSS) in patients treated with radical nephroureterectomy (RNU) for UTUC.
Prospectively collected data were retrospectively reviewed from 324 consecutive patients treated with RNU between 1995 and 2008 at a single tertiary referral center. Patients who had previous radical cystectomy, preoperative chemotherapy, previous contralateral UTUC, or metastatic disease at presentation were excluded. This left 253 patients for analysis. Tumor location was categorized as renal pelvis or ureter based on the location of the dominant tumor. Recurrences in the bladder only, in nonbladder sites, and in any site were analyzed.
All patients were treated with RNU.
Recurrence-free survival and CSS probabilities were estimated using Kaplan-Meier and Cox regression analyses.
Median follow-up for survivors was 48 mo. The 5-yr recurrence-free probability (including bladder recurrence) and CSS estimates were 32% and 78%, respectively. On multivariable analysis, pathologic stage was the only predictor for disease recurrence (p=0.01). Tumor location was not an independent predictor for recurrence (hazard ratio: 1.19; p=0.3), and there was no difference in the probability of disease recurrence between ureteral and renal pelvic tumors (p=0.18). On survival analysis, we also found no differences between ureteral and renal pelvic tumors on probability of CSS (p=0.2). On multivariate analysis, pathologic stage (p<0.0001) and nodal status (p=0.01) were associated with worse CSS. This study is limited by its retrospective nature.
Our study did not show any differences in recurrence and CSS rates between patients with ureteral and renal pelvic tumors treated with RNU.
European urology 10/2010; 58(4):574-80. · 7.67 Impact Factor
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Matthew G Kaag,
Rebecca L O'Malley,
Padraic O'Malley,
Guilherme Godoy,
Mang Chen,
Marc C Smaldone,
Ronald L Hrebinko,
Jay D Raman,
Bernard Bochner, Guido Dalbagni,
Michael D Stifelman,
Samir S Taneja,
William C Huang
[show abstract]
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ABSTRACT: Nephroureterectomy alone fails to adequately treat many patients with advanced upper tract urothelial carcinoma (UTUC). Perioperative platinum-based chemotherapy has been proposed but requires adequate renal function.
Our aim was to determine whether the ability to deliver platinum-based chemotherapy following nephroureterectomy is affected by postoperative changes in renal function.
We retrospectively reviewed data on 388 patients undergoing nephroureterectomy for UTUC between 1991 and 2009. Four institutions were included.
All patients underwent nephroureterectomy.
All patients had serum creatinine measured before and after surgery. The value closest to 3 mo after surgery was taken as the postoperative value (range: 2-52 wk). Estimated glomerular filtration rate (eGFR) was calculated using the abbreviated Modification of Diet in Renal Disease study equation. eGFR values before and after surgery were compared using the paired t test. We chose an eGFR of 45 and 60 ml/min per 1.73 m(2) as possible cut-offs for chemotherapy eligibility and compared eligibility before and after surgery using the chi-square test.
Our cohort of 388 patients included 233 men (60%) with a median age of 70 yr. Mean eGFR decreased by 24% after surgery. Using a cut-off of 60 ml/min per 1.73 m(2), 49% of patients were eligible for chemotherapy before surgery, but only 19% of patients remained eligible postoperatively. Using a cut-off of 45 ml/min per 1.73 m(2), 80% of patients were eligible preoperatively, but only 55% remained eligible after surgery. This distribution persisted when we limited the analysis to patients with advanced pathologic stage (T3 or higher). Patients older than the median age of 70 yr were more likely to be ineligible for chemotherapy both pre- and postoperatively by either definition, and they were significantly more likely to have an eGFR <45 ml/min per 1.73 m(2) postoperatively, regardless of their starting eGFR. This study is limited by its retrospective nature, and there was some variability in the timing of postoperative serum creatinine measurements.
eGFR is significantly diminished after nephroureterectomy, particularly in elderly patients. These changes in renal function likely affect eligibility for adjuvant cisplatin-based therapy. Accordingly, we suggest strong consideration of neoadjuvant regimens.
European urology 10/2010; 58(4):581-7. · 7.67 Impact Factor
