News Article | April 18, 2017
Philadelphia, PA, April 18, 2017 - In the past, all forms of metastatic prostate cancer have been considered incurable. In recent years, the FDA has approved six drugs for men with metastatic disease, all of which can increase survival. In a study published in Urology®, researchers demonstrate for the first time that an aggressive combination of systemic therapy (drug treatment) with local therapy (surgery and radiation) directed at both the primary tumor and metastasis can eliminate all detectable disease in selected patients with metastatic prostate cancer. While the study is only a first step, one-fifth of the patients treated had no detectable disease, with an undetectable prostate-specific-androgen (PSA) and normal blood testosterone, after 20 months. The results suggest that some men who have previously been considered incurable can possibly be cured; investigators also establish a new paradigm for testing various drug combinations in conjunction with local treatment of the prostate to determine which is the best approach (ie, has the highest undetectable disease rate). Such results could not have been achieved with any single therapy alone. According to lead investigator Howard I. Scher, MD, Chief of the Genitourinary Oncology Service at Memorial Sloan Kettering Cancer Center in New York City, "The sequential use of the three different modalities helped illustrate the role and importance of each in achieving the undetectable PSA with normal testosterone level end point, which represents a 'no-evidence of disease' status." Longer follow-up is needed to determine whether these patients were in fact cured. Twenty men with metastatic prostate cancer, five with extra-pelvic lymph nodal disease and 15 with bone with or without nodal disease, were treated with androgen deprivation therapy (ADT), radical surgery that included a retroperitoneal lymph node dissection as needed, and radiation therapy to visible metastatic lesions in bone. ADT was stopped after a minimum of six months if an undetectable PSA was achieved after combined modality therapy. Other patients were treated continuously. The combined treatment regimen including surgery was well tolerated. Matthew J. O'Shaughnessy, MD, PhD, Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, commented "While the role of local therapy in metastatic prostate cancer is still under investigation, aggressive resection of visible disease performed by experienced surgeons was critical to the outcome." Of the five patients with extra-pelvic lymph node involvement, four achieved an undetectable PSA after ADT and surgery, while the fifth needed radiation to reach this milestone. However, none achieved the primary end point of undetectable PSA with testosterone recovery at 20 months after initiation of therapy with ADT alone, although one patient had a PSA of Of the 15 patients with bone metastases, 14 (93%) reached an undetectable PSA when ADT, surgery, and radiation were used. Ultimately, four (27%) achieved the proposed end point, a PSA of 150 ng/dL at 20 months after the start of ADT, which remained undetectable in two patients for 27 and 46 months, respectively. Commenting on the study, Oliver Sartor, MD, Cancer Research, Department of Medicine and Urology, Tulane University School of Medicine, New Orleans, LA, stated, "The end point deserves special mention, as the end point of undetectable PSA after testosterone recovery has been previously discussed but rarely studied. The authors proposed that this end point may serve as a first step toward establishing a curative paradigm. Many in the field agree, but note that the longevity of effect is essential to prove the point of curability. Regardless, the movement toward a curative paradigm is much needed and the investigators are to be congratulated for setting forth a paradigm that can be used to assess the possibility of cure in a reasonable period of time." "A multimodal treatment strategy for patients who present with disease that is beyond the limits of curability by any single modality enables the evaluation of new approaches in order to prioritize large-scale testing in early stages of advanced disease. The end point also shifts the paradigm from palliation to cure," remarked Dr. Scher. It is expected that an upcoming Phase 2 trial will further test this endpoint and combined modality approach.
Bazzi W.M.,Sloan Kettering Cancer Center |
Sjoberg D.D.,Sloan Kettering Cancer Center |
Feuerstein M.A.,Sloan Kettering Cancer Center |
Maschino A.,Sloan Kettering Cancer Center |
And 6 more authors.
Journal of Urology | Year: 2015
Purpose We analyzed the 23-year Memorial Sloan Kettering Cancer Center experience with surgical resection, and concurrent adrenalectomy and lymphadenectomy for locally advanced nonmetastatic renal cell carcinoma. Materials and Methods We retrospectively reviewed the records of 802 patients who underwent nephrectomy with or without concurrent adrenalectomy or lymphadenectomy for locally advanced renal cell carcinoma, defined as stage T3 or greater and M0. Patients who received adjuvant treatment within 3 months of surgery or had fewer than 3 months of followup or bilateral renal masses at presentation were excluded from analysis. Five and 10-year progression-free and overall survival was estimated by the Kaplan-Meier method. Differences between groups were analyzed by the log rank test. Results A total of 596 (74%) and 206 patients (26%) underwent radical and partial nephrectomy, respectively. Renal cell carcinoma progressed in 189 patients and 104 died of the disease. Median followup in patients without progression was 4.6 years. Symptoms at presentation, ASA® classification, tumor stage, histological subtype, grade and lymph node status were significantly associated with progression-free and overall survival. On multivariate analysis adrenalectomy use decreased with time but lymphadenectomy use increased (OR 0.82 vs 1.16 per year). Larger tumors were associated with a higher likelihood of concurrent adrenalectomy and lymphadenectomy. Conclusions In our series of patients with locally advanced nonmetastatic renal cell carcinoma survival was favorable in those in good health who were asymptomatic at presentation with T3 tumors and negative lymph nodes. Further, there has been a trend toward more selective use of adrenalectomy and increased use of lymphadenectomy. © 2015 American Urological Association Education and Research, Inc.
Hakimi A.A.,Urology Service |
Liu H.,Sloan Kettering Cancer Center |
Takeda S.,Sloan Kettering Cancer Center |
Voss M.H.,Sloan Kettering Cancer Center |
And 4 more authors.
Clinical Cancer Research | Year: 2013
Purpose: To investigate the impact of newly identified chromosome 3p21 epigenetic tumor suppressors PBRM1, SETD2, and BAP1 on cancer-specific survival (CSS) of 609 patients with clear cell renal cell carcinoma (ccRCC) from 2 distinct cohorts. Experimental Design: Select sequencing on 3p tumor suppressors of 188 patients who underwent resection of primary ccRCC at the Memorial Sloan-Kettering Cancer Center (MSKCC) was conducted to interrogate the genotype-phenotype associations. These findings were compared with analyses of the genomic and clinical dataset from our nonoverlapping The Cancer Genome Atlas (TCGA) cohort of 421 patients with primary ccRCC. Results: 3p21 tumor suppressors are frequently mutated in both the MSKCC (PBRM1, 30.3%; SETD2, 7.4%; BAP1, 6.4%) and the TCGA (PBRM1, 33.5%; SETD2, 11.6%; BAP1, 9.7%) cohorts. BAP1 mutations are associated with worse CSS in both cohorts [MSKCC, P = 0.002; HR 7.71; 95% confidence interval (CI) 2.08-28.6; TCGA, P = 0.002; HR 2.21; 95% CI 1.35-3.63]. SETD2 are associated with worse CSS in the TCGA cohort (P = 0.036; HR1.68; 95%CI 1.04-2.73). On the contrary, PBRM1 mutations, the second most common gene mutations of ccRCC, have no impact on CSS. Conclusion: The chromosome 3p21 locus harbors 3 frequently mutated ccRCC tumor suppressor genes. BAP1 and SETD2 mutations (6%-12%) are associated with worse CSS, suggesting their roles in disease progression. PBRM1 mutations (30%-34%) do not impact CSS, implicating its principal role in the tumor initiation. Future efforts should focus on therapeutic interventions and further clinical, pathologic, and molecular interrogation of this novel class of tumor suppressors. © 2013 American Association for Cancer Research.
Chen Y.-B.,Sloan Kettering Cancer Center |
Brannon A.R.,Sloan Kettering Cancer Center |
Toubaji A.,Sloan Kettering Cancer Center |
Dudas M.E.,Sloan Kettering Cancer Center |
And 9 more authors.
American Journal of Surgical Pathology | Year: 2014
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome is an autosomal dominant disorder in which germline mutations of fumarate hydratase (FH) gene confer an increased risk of cutaneous and uterine leiomyomas and renal cancer. HLRCC-associated renal cancer is highly aggressive and frequently presents as a solitary mass. We reviewed the clinicopathologic features of 9 patients with renal tumors presenting as sporadic cases but who were later proven to have FH germline mutations. Histologically, all tumors showed mixed architectural patterns, with papillary as the dominant pattern in only 3 cases. Besides papillary, tubular, tubulopapillary, solid, and cystic elements, 6 of 9 tumors contained collecting duct carcinoma-like areas with infiltrating tubules, nests, or individual cells surrounded by desmoplastic stroma. Prominent tubulocystic carcinoma-like component and sarcomatoid differentiation were identified. Although all tumors exhibited the proposed hallmark of HLRCC (large eosinophilic nucleolus surrounded by a clear halo), this feature was often not uniformly present throughout the tumor. Prior studies have shown that a high level of fumarate accumulated in HLRCC tumor cells causes aberrant succination of cellular proteins by forming a stable chemical modification, S-(2-succino)-cysteine (2SC), which can be detected by immunohistochemistry. We thus explored the utility of detecting 2SC by immunohistochemistry in the differential diagnosis of HLRCC tumors and other high-grade renal tumors and investigated the correlation between 2SC staining and FH molecular alterations. All confirmed HLRCC tumors demonstrated diffuse and strong nuclear and cytoplasmic 2SC staining, whereas all clear cell (184/184, 100%), most high-grade unclassified (93/97, 96%), and the large majority of "type 2" papillary (35/45, 78%) renal cell carcinoma cases showed no 2SC immunoreactivity. A subset of papillary (22%) and rare unclassified (4%) tumors showed patchy or diffuse cytoplasmic staining without nuclear labeling, unlike the pattern seen with confirmed HLRCC tumors. Sequencing revealed no germline or somatic FH alterations in 14 tumors that either exhibited only cytoplasmic 2SC staining (n=5) or were negative for 2SC (n=9), despite their HLRCC-like morphologic features. Our results emphasize the pivotal role of pathologic examination in the diagnosis of HLRCC patients and indicate immunohistochemical detection of 2SC as a useful ancillary tool in the differentiation of HLRCC renal tumors from other high-grade renal cell carcinomas. © 2014 by Lippincott Williams and Wilkins.
Wiedemann L.,University Paris Est Creteil |
Cornu J.-N.,University Paris Est Creteil |
Haab E.,University Paris Est Creteil |
Peyrat L.,University Paris Est Creteil |
And 4 more authors.
BJU International | Year: 2013
Objectives To describe the surgical technique of transcorporal artificial urinary sphincter (AUS) implantation. To assess the efficacy of the AUS on continence and erectile function. Patients and Methods A prospective evaluation was conducted between December 2007 and October 2012 at a tertiary referral centre of all male patients treated by transcorporal AUS (AMS800™, AmericanMedicalSystems, Minnetonka, MN, USA) implantation for stress urinary incontinence (SUI) recurrence, after failure of previous anti-incontinence surgery. Functional urinary outcomes were assessed according to daily pad use, the Urinary Symptom Profile questionnaire, and International Consultation on Incontinence Questionnaire - Short-Form. Erectile function was evaluated using the five-item International Index of Erectile Function (IIEF-5) questionnaire and patient satisfaction was assessed by Patient Global Impression of Improvement questionnaire. Data were collected by telephone interview. Results A total of 23 patients were included. Their mean (sd; range) age was 70 (7; 60-85) years. Of these, 18 patients had urethral atrophy and/or erosion after placement of AUS (11 patients), male sling (four patients) or both (three patients), and five patients had severe urethral atrophy after pelvic radiation therapy. The implantation of the AUS with transcorporal cuff placement was successful in all patients, with no peri-operative complications. Follow-up data over 1 year were available for 17 patients. After a median (sd; range) follow-up of 20 (15; 2-59) months, eight patients were perfectly dry (no pad use and no symptoms), five achieved social continence (less than one pad/day), and four still had SUI (required two or more pads/day). Among six patients who had good preoperative erectile function and were sexually active, four had no decrease in their IIEF-5 score. Conclusions Transcorporal AUS cuff placement is a useful alternative for challenging cases of male SUI after failure of previous surgical treatment, urethral atrophy or erosion. Erectile function can be maintained despite dissection of the corporal body. © 2013 BJU International.
Stattin P.,Umeå University |
Carlsson S.,Urology Service |
Carlsson S.,Gothenburg University |
Holmstrom B.,Umeå University |
And 7 more authors.
Journal of the National Cancer Institute | Year: 2014
Background The effect of prostate-specific antigen (PSA) screening on prostate cancer mortality remains debated, despite evidence from randomized trials. We investigated the association between prostate cancer incidence, reflecting uptake of PSA testing, and prostate cancer mortality. Methods The study population consisted of all men aged 50 to 74 years residing in eight counties in Sweden with an early increase in prostate cancer incidence and six counties with a late increase during two time periods. Incidence of metastatic prostate cancer was investigated in the period from 2000 to 2009, and prostate cancer-specific mortality and excess mortality were investigated in the period from 1990 to 1999 and the period from 2000 to 2009 by calculating rate ratios for high- vs low-incidence counties and rate ratios for the period from 2000 to 2009 vs the period from 1990 to 1999 within these two groups. All statistical tests were two-sided. Results There were 4 528 134 person-years at risk, 1577 deaths from prostate cancer, and 1210 excess deaths in men with prostate cancer in high-incidence counties and 2 471 373 person-years at risk, 985 prostate cancer deaths, and 878 excess deaths in low-incidence counties in the period from 2000 to 2009. Rate ratios in counties with high vs low incidence adjusted for time period were 0.81 (95% confidence interval [CI] = 0.73 to 0.90) for prostate cancer-specific mortality and 0.74 (95% CI = 0.64 to 0.86) for excess mortality, and the rate ratio of metastatic prostate cancer was 0.85 (95% CI = 0.79 to 0.92). Conclusions The lower prostate cancer mortality in high-incidence counties reflecting a high PSA uptake suggests that moreintense as compared with less-intense opportunistic PSA screening reduces prostate cancer mortality. © The Author 2014.
Cronin A.M.,Urology Service |
Godoy G.,Urology Service |
Vickers A.J.,Urology Service
Journal of Urology | Year: 2010
Purpose: Biochemical recurrence serves as a surrogate end point after radical prostatectomy. Many definitions of biochemical recurrence are currently used in the research literature. We examined various definitions in a large clinical cohort to explore whether estimation differs by definition. Materials and Methods: The cohort included 5,473 patients who underwent radical prostatectomy from 1985 to 2007 at our cancer center. Separate analysis was done with 12 definitions of biochemical recurrence used in published studies. Cox regression was done to estimate HRs for established predictors. Predictive accuracy was determined using the concordance index. Results: Depending on the definition the recurrence-free probability was 86% to 91% at 3 years and 81% to 87% at 5 years. HRs tended to be smaller for the most inclusive definitions but were fairly similar across all definitions. The univariate HR was 2.1 to 2.4 for log prostate specific antigen, 2.4 to 2.6 for clinical stage T2b vs T2a or less and 9.8 to 15 for biopsy Gleason grade 8 or greater vs 6 or less. Multivariate HRs were more homogeneous across the definitions. The concordance index was 0.79 to 0.83 and 0.83 to 0.87 for the preoperative and postoperative nomograms, respectively. Conclusions: Estimates of risk ratios and predictive accuracy are generally robust to the biochemical recurrence definition. For clinical research, groups using different definitions will come to similar conclusions on prognostic factors. The definition should be factored into studies comparing overall recurrence probabilities. © 2010 American Urological Association Education and Research, Inc.
Kim P.H.,Urology Service |
Sukhu R.,Sloan Kettering Cancer Center |
Cordon B.H.,Urology Service |
Sfakianos J.P.,Urology Service |
And 5 more authors.
BJU International | Year: 2014
Objective To assess the ability of reflex UroVysion fluorescence in situ hybridization (FISH) testing to predict recurrence and progression in patients with non-muscle-invasive bladder cancer (NMIBC) with suspicious cytology but negative cystoscopy. Patients and Methods Patients under NMIBC surveillance were followed with office cystoscopy and urinary cytology every 3-6 months. Between March 2007 and February 2012, 500 consecutive patients with suspicious cytology underwent reflex FISH analysis. Clinical and pathological data were reviewed retrospectively. Predictors for recurrence, progression and findings on subsequent cystoscopy (within 2-6 months after FISH) were evaluated using univariate and multivariate Cox regression. Results In all, 243 patients with suspicious cytology also had negative surveillance cystoscopy. Positive FISH was a significant predictor of recurrence (hazard ratio [HR] = 2.35, 95% confidence interval [CI]: 1.42-3.90, P = 0.001) in multivariate analysis and for progression (HR = 3.01, 95% CI: 1.10-8.21, P = 0.03) in univariate analysis, compared with negative FISH. However, positive FISH was not significantly associated with evidence of tumour on subsequent surveillance cystoscopy compared with negative FISH (odds ratio = 0.8, 95% CI: 0.26-2.74, P = 1). Conclusions Positive FISH predicts recurrence and progression in patients under NMIBC surveillance with suspicious cytology but negative cystoscopy. However, there was no association between the FISH result and tumour recurrence in the immediate follow-up period. Reflex FISH testing for suspicious cytology might have limited ability to modify surveillance strategies in NMIBC. © 2013 The Authors. BJU International © 2013 BJU International.
Sprenkle P.C.,Urology Service |
Wren J.,Urology Service |
Maschino A.C.,Clinical Chemistry Service |
Feifer A.,Urology Service |
And 4 more authors.
Journal of Urology | Year: 2013
Purpose: We evaluated urine NGAL as a marker of acute kidney injury in patients undergoing partial nephrectomy. We sought to identify the preoperative clinical features and surgical factors during partial nephrectomy that are associated with renal injury, as measured by increased urine NGAL vs controls. Materials and Methods: Using patients treated with radical nephrectomy or thoracic surgery as controls, we prospectively collected and analyzed urine and serum samples from patients treated with partial or radical nephrectomy, or thoracic surgery between April 2010 and April 2012. Urine was collected preoperatively and at multiple time points postoperatively. Differences in urine NGAL levels were analyzed among the 3 surgical groups using a generalized estimating equation model. The partial nephrectomy group was subdivided based on a preoperative estimated glomerular filtration rate of less than 60, or 60 ml/minute/1.73 m2 or greater. Results: Of 162 patients included in final analysis more than 65% had cardiovascular disease. The median estimated glomerular filtration rate was greater than 60 ml/minute/1.73 m2 in the radical and partial nephrectomy, and thoracic surgery groups (61, 78 and 84.5 ml/minute/1.73 m2, respectively). Preoperatively, a 10 unit increase in the estimated glomerular filtration rate was associated with a 4 unit decrease in urine NGAL in the partial nephrectomy group. Postoperatively, urine NGAL in the partial nephrectomy group was not higher than in controls and did not correlate with ischemia time. Patients with partial nephrectomy with a preoperative estimated glomerular filtration rate of less than 60 ml/minute/1.73 m2 had higher urine NGAL postoperatively than those with a higher preoperative estimated rate. Conclusions: Urine NGAL does not appear to be a useful marker for detecting renal injury in healthy patients treated with partial nephrectomy. However, patients with poorer preoperative renal function have higher baseline urine levels and appear more susceptible to acute kidney injury, as detected by urine levels and Acute Kidney Injury Network criteria, than those with a normal estimated glomerular filtration rate. © 2013 American Urological Association Education and Research, Inc.
Poon S.A.,Urology Service |
Silberstein J.L.,Urology Service |
Chen L.Y.,Urology Service |
Chen L.Y.,Sloan Kettering Cancer Center |
And 3 more authors.
Journal of Urology | Year: 2013
Purpose: Surgical treatment options for renal masses include radical vs partial nephrectomy and the open vs laparoscopic approach. Using American Board of Urology (ABU) case log data, we investigated contemporary trends in these treatment options, and how surgeon and practice characteristics may influence these trends. Materials and Methods: Annualized case log data for nephrectomy were obtained from the ABU for all urologists certifying or recertifying from 2002 to 2010. We evaluated trends in nephrectomy use. Logistic regression was used to evaluate surgeon and practice characteristics as predictors of partial and laparoscopic procedures. Results: From the 3,852 case logs submitted by nonpediatric urologists we analyzed a total of 48,384 nephrectomies. From 2002 to 2010 the proportion of annual nephrectomies performed as open radical nephrectomy gradually decreased from 54% to 29%. During the same period, there was a moderate gradual increase in laparoscopic radical nephrectomies (from 30% to 39%). The proportion of open partial nephrectomies remained stable at 15%, while laparoscopic partial nephrectomy increased from 2% to 17%. On multivariable analysis the use of partial nephrectomy and laparoscopy was predicted by urologist annual nephrectomy volume, initial or recertification status, subspecialty, practice area size and geographic region. Conclusions: Since 2002, the use of laparoscopic nephrectomy and partial nephrectomy has increased. However, the diffusion of these techniques is not uniform. Initial certification, higher surgical volume, and practicing in areas with more than 1,000,000 population and in the Northeast region were associated with greater use of laparoscopy and partial nephrectomy. Factors that affect the adoption of these techniques require further research. © 2013 American Urological Association Education and Research, Inc.