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Urinary Bladder Neoplasms: HELP
Articles by Harry W. Herr
Based on 87 articles published since 2010
(Why 87 articles?)
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Between 2010 and 2020, H. W. Herr wrote the following 87 articles about Urinary Bladder Neoplasms.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4
1 Guideline NCCN Guidelines Insights: Bladder Cancer, Version 5.2018. 2018

Flaig, Thomas W / Spiess, Philippe E / Agarwal, Neeraj / Bangs, Rick / Boorjian, Stephen A / Buyyounouski, Mark K / Downs, Tracy M / Efstathiou, Jason A / Friedlander, Terence / Greenberg, Richard E / Guru, Khurshid A / Hahn, Noah / Herr, Harry W / Hoimes, Christopher / Inman, Brant A / Jimbo, Masahito / Kader, A Karim / Lele, Subodh M / Meeks, Joshua J / Michalski, Jeff / Montgomery, Jeffrey S / Pagliaro, Lance C / Pal, Sumanta K / Patterson, Anthony / Petrylak, Daniel P / Plimack, Elizabeth R / Pohar, Kamal S / Porter, Michael P / Preston, Mark A / Sexton, Wade J / Siefker-Radtke, Arlene O / Tward, Jonathan / Wile, Geoffrey / Johnson-Chilla, Alyse / Dwyer, Mary A / Gurski, Lisa A. · ·J Natl Compr Canc Netw · Pubmed #30181416.

ABSTRACT: The NCCN Clinical Practice Guidelines in Oncology for Bladder Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with bladder cancer. These NCCN Guidelines Insights discuss important updates to the 2018 version of the guidelines, including implications of the 8th edition of the AJCC Cancer Staging Manual on treatment of muscle-invasive bladder cancer and incorporating newly approved immune checkpoint inhibitor therapies into treatment options for patients with locally advanced or metastatic disease.

2 Guideline Bladder Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology. 2017

Spiess, Philippe E / Agarwal, Neeraj / Bangs, Rick / Boorjian, Stephen A / Buyyounouski, Mark K / Clark, Peter E / Downs, Tracy M / Efstathiou, Jason A / Flaig, Thomas W / Friedlander, Terence / Greenberg, Richard E / Guru, Khurshid A / Hahn, Noah / Herr, Harry W / Hoimes, Christopher / Inman, Brant A / Jimbo, Masahito / Kader, A Karim / Lele, Subodh M / Meeks, Joshua J / Michalski, Jeff / Montgomery, Jeffrey S / Pagliaro, Lance C / Pal, Sumanta K / Patterson, Anthony / Plimack, Elizabeth R / Pohar, Kamal S / Porter, Michael P / Preston, Mark A / Sexton, Wade J / Siefker-Radtke, Arlene O / Sonpavde, Guru / Tward, Jonathan / Wile, Geoffrey / Dwyer, Mary A / Gurski, Lisa A. · ·J Natl Compr Canc Netw · Pubmed #28982750.

ABSTRACT: This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on systemic therapy for muscle-invasive urothelial bladder cancer, as substantial revisions were made in the 2017 updates, such as new recommendations for nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab. The complete version of the NCCN Guidelines for Bladder Cancer addresses additional aspects of the management of bladder cancer, including non-muscle-invasive urothelial bladder cancer and nonurothelial histologies, as well as staging, evaluation, and follow-up.

3 Guideline Bladder cancer. 2013

Clark, Peter E / Agarwal, Neeraj / Biagioli, Matthew C / Eisenberger, Mario A / Greenberg, Richard E / Herr, Harry W / Inman, Brant A / Kuban, Deborah A / Kuzel, Timothy M / Lele, Subodh M / Michalski, Jeff / Pagliaro, Lance C / Pal, Sumanta K / Patterson, Anthony / Plimack, Elizabeth R / Pohar, Kamal S / Porter, Michael P / Richie, Jerome P / Sexton, Wade J / Shipley, William U / Small, Eric J / Spiess, Philippe E / Trump, Donald L / Wile, Geoffrey / Wilson, Timothy G / Dwyer, Mary / Ho, Maria / Anonymous4410755. ·Vanderbilt-Ingram Cancer Center. ·J Natl Compr Canc Netw · Pubmed #23584347.

ABSTRACT: Bladder cancer is the fourth most common cancer in the United States. Urothelial carcinoma that originates from the urinary bladder is the most common subtype. These NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) provide recommendations on the diagnosis and management of non-muscle-invasive and muscle-invasive urothelial carcinoma of the bladder. This version of the guidelines provides extensive reorganization and updates on the principles of chemotherapy management.

4 Editorial Editorial comment. 2012

Herr, Harry W. · ·Urology · Pubmed #22516353.

ABSTRACT: -- No abstract --

5 Editorial Kuhn's paradigms: are those closest to treating bladder cancer the last to appreciate the paradigm shift? 2011

Bajorin, Dean F / Herr, Harry W. · ·J Clin Oncol · Pubmed #21502548.

ABSTRACT: -- No abstract --

6 Editorial Editorial comment. 2010

Herr, Harry W. · ·Urology · Pubmed #20152490.

ABSTRACT: -- No abstract --

7 Editorial Editorial comment. 2010

Herr, Harry W. · ·Urology · Pubmed #20152487.

ABSTRACT: -- No abstract --

8 Review Cystoscopy and intravesical bacille Calmette-Guérin therapy in antibiotic-naïve patients with bladder cancer with asymptomatic bacteriuria: An update. 2016

Herr, Harry W. ·Department of Urology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. ·Arab J Urol · Pubmed #27489733.

ABSTRACT: Urologists often insist on sterile urine before invasive outpatient urological procedures, and urine culture and antibiotics are usually given before cystoscopy or instillation of bacille Calmette-Guérin (BCG) therapy, especially in patients who have positive urine cultures. Our experience suggests that cystoscopy and induction BCG therapy can be performed safely, even in patients with asymptomatic bacteriuria, without pretreatment or prophylactic antibiotics. The rate of subsequent febrile urinary tract infection is <4% in both infected and uninfected patients. Pretreatment antibacterial therapy does not appear to be necessary before these two outpatient urological procedures in patients with bladder cancer. Such strategy facilitates timely interventions and reduces the possibility of antibiotic resistance.

9 Review Role of Repeat Resection in Non-Muscle-Invasive Bladder Cancer. 2015

Herr, Harry W. ·From Memorial Sloan Kettering Cancer Center, New York, New York. ·J Natl Compr Canc Netw · Pubmed #26285248.

ABSTRACT: Repeat transurethral resection (TUR) is indicated for high-grade non-muscle-invasive bladder tumors. Repeat TUR is a diagnostic, therapeutic, prognostic, and predictive procedure. Repeat TUR achieves optimal local control by removing residual tumors after initial TUR, improves staging accuracy, provides additional histologic material favoring accurate diagnosis, allocates appropriate therapy with improved outcomes, facilitates response to intravesical therapy, and provides important prognostic information.

10 Review Clinical value of transurethral second resection of bladder tumor: systematic review. 2014

Dobruch, Jakub / Borówka, Andrzej / Herr, Harry W. ·Department of Urology, Center of Postgraduate Medical Education, Warsaw, Poland; Young Academic Urologists of European Association of Urology Bladder Cancer Group. Electronic address: kubadobr@wp.pl. · Department of Urology, Center of Postgraduate Medical Education, Warsaw, Poland. · Department of Urology, Memorial Sloan Kettering Cancer Center, New York, NY. ·Urology · Pubmed #25129540.

ABSTRACT: OBJECTIVE: To systematically review prospective trials aimed at the role of restaging transurethral resection (reTUR) to define the group of patients with bladder cancer who would benefit. MATERIALS AND METHODS: A systematic review of the literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines was conducted. RESULTS: Of 120 trials, 7 met the inclusion criteria. Most studied populations were high-risk non-muscle-invasive bladder cancer patients. Low-risk cancers as well as muscle-invasive disease were analyzed in only 1 trial. Consistently through the publications, reTUR improved staging with the rates of muscle-invasive disease mounting to 17.6% when primary resection was deemed to be complete. Although all trials corroborated staging role of reTUR, only 4 provided recurrence and progression outcomes, the first being significantly lower in the group of second early resection. In 2 studies with the longest follow-up and the greatest number of patients with high-risk non-muscle-invasive bladder cancer, progression rates were found to be improved. In one trial, reTUR was associated with better response to bacille Calmette-Guérin. CONCLUSION: The data convincingly suggest that early second resection improves staging and reduces the recurrence as well as progression rates of high-risk bladder tumors. reTUR brings benefit to those subjected to bacille Calmette-Guérin. However, additional surgery would not modify treatment plan in those with low-risk disease.

11 Review Narrow-band imaging evaluation of bladder tumors. 2014

Herr, Harry W. ·Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA, herrh@mskcc.org. ·Curr Urol Rep · Pubmed #24652533.

ABSTRACT: Narrow-band imaging (NBI) is a novel optical method designed to enhance visual detection of bladder tumors over conventional white-light imaging (WLI) cystoscopy. Current experience with NBI cystoscopy in evaluating and treating non-muscle-invasive bladder tumors is reviewed. A comprehensive literature search was conducted including all published studies and abstracts investigating NBI cystoscopy in patients with bladder cancer. Comprehensive cystoscopic images are provided to illustrate differences between NBI and WLI cystoscopy. Early experience suggests that NBI cystoscopy detects more bladder tumors than does WLI cystoscopy, and NBI-assisted fulguration and transurethral resection (TUR) appear to result in fewer tumor recurrences. Questions remain, however, such as the following: Does NBI cystoscopy detect high-grade tumors, such as carcinoma in situ, that are missed by WLI cystoscopy? Would false positives lead to an unaccepted number of negative biopsies? And how might observer bias skew results? In addition, a major drawback of current studies is that the quality of cystoscopy and TUR by individual surgeons has not been addressed. Although clinical trials are just beginning, NBI cystoscopy holds promise that this new optical method may improve visualization of bladder tumors over conventional WLI cystoscopy. Further prospective and comparative trials are required to determine whether NBI will play a role in evaluating and treating urothelial tumors in individual patients.

12 Review Critical analysis of bladder sparing with trimodal therapy in muscle-invasive bladder cancer: a systematic review. 2014

Ploussard, Guillaume / Daneshmand, Siamak / Efstathiou, Jason A / Herr, Harry W / James, Nicholas D / Rödel, Claus M / Shariat, Shahrokh F / Shipley, William U / Sternberg, Cora N / Thalmann, George N / Kassouf, Wassim. ·Department of Surgery, Division of Urology, McGill University, Montreal, Quebec, Canada; Department of Urology, Saint-Louis Hospital, Assistance Publique Hôpitaux de Paris, Paris, France. · University of Southern California Institute of Urology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA. · Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. · Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. · University of Birmingham, School of Cancer Sciences, Edgbaston, Birmingham, UK. · Department of Radiotherapy and Oncology, University of Frankfurt, Frankfurt, Germany. · Department of Urology, Medical University of Vienna, Vienna, Austria. · Department of Medical Oncology, San Camillo Forlanini Hospital, Rome, Italy. · Department of Urology, University of Berne, Berne, Switzerland. · Department of Surgery, Division of Urology, McGill University, Montreal, Quebec, Canada. Electronic address: wassim.kassouf@muhc.mcgill.ca. ·Eur Urol · Pubmed #24613684.

ABSTRACT: CONTEXT: Aims of bladder preservation in muscle-invasive bladder cancer (MIBC) are to offer a quality-of-life advantage and avoid potential morbidity or mortality of radical cystectomy (RC) without compromising oncologic outcomes. Because of the lack of a completed randomised controlled trial, oncologic equivalence of bladder preservation modality treatments compared with RC remains unknown. OBJECTIVE: This systematic review sought to assess the modern bladder-preservation treatment modalities, focusing on trimodal therapy (TMT) in MIBC. EVIDENCE ACQUISITION: A systematic literature search in the PubMed and Cochrane databases was performed from 1980 to July 2013. EVIDENCE SYNTHESIS: Optimal bladder-preservation treatment includes a safe transurethral resection of the bladder tumour as complete as possible followed by radiation therapy (RT) with concurrent radiosensitising chemotherapy. A standard radiation schedule includes external-beam RT to the bladder and limited pelvic lymph nodes to an initial dose of 40 Gy, with a boost to the whole bladder to 54 Gy and a further tumour boost to a total dose of 64-65 Gy. Radiosensitising chemotherapy with phase 3 trial evidence in support exists for cisplatin and mitomycin C plus 5-fluorouracil. A cystoscopic assessment with systematic rebiopsy should be performed at TMT completion or early after TMT induction. Thus, nonresponders are identified early to promptly offer salvage RC. The 5-yr cancer-specific survival and overall survival rates range from 50% to 82% and from 36% to 74%, respectively, with salvage cystectomy rates of 25-30%. There are no definitive data to support the benefit of using of neoadjuvant or adjuvant chemotherapy. Critical to good outcomes is proper patient selection. The best cancers eligible for bladder preservation are those with low-volume T2 disease without hydronephrosis or extensive carcinoma in situ. CONCLUSIONS: A growing body of accumulated data suggests that bladder preservation with TMT leads to acceptable outcomes and therefore may be considered a reasonable treatment option in well-selected patients. PATIENT SUMMARY: Treatment based on a combination of resection, chemotherapy, and radiotherapy as bladder-sparing strategies may be considered as a reasonable treatment option in properly selected patients.

13 Review Office-based management of nonmuscle invasive bladder cancer. 2013

Meeks, Joshua J / Herr, Harry W. ·Department of Urology, Northwestern University, Feinberg School of Medicine, 303 East Chicago Avenue, Tarry 16-703, Chicago, IL 60611, USA. ·Urol Clin North Am · Pubmed #24182970.

ABSTRACT: Bladder cancer is extremely common in the United States and extremely costly because of the high cost of surveillance. In some patients, office-based surveillance may be a safe, cost-reducing alternative. This article attempts to identify ideal candidates and highlights surveillance strategies that can be employed in an office-based setting.

14 Review Maintenance bacillus Calmette-Guérin treatment of non-muscle-invasive bladder cancer: a critical evaluation of the evidence. 2013

Ehdaie, Behfar / Sylvester, Richard / Herr, Harry W. ·Urology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. ehdaieb@mskcc.org ·Eur Urol · Pubmed #23711538.

ABSTRACT: CONTEXT: Despite the effectiveness of bacillus Calmette-Guérin (BCG) therapy in non-muscle-invasive bladder cancer (NIMBC) to delay recurrence and disease progression, the evidence supporting maintenance treatment and its optimal duration is unkown. OBJECTIVE: The purposes of this paper are to critically review the evidence supporting the use of maintenance BCG after an initial series of induction instillations and to illustrate the factors contributing to current dilemmas in establishing the optimal duration of BCG treatment. EVIDENCE ACQUISITION: The following terms were used in Medline database searches for original articles published before February 1, 2013: bladder cancer, urothelial cancer, bacillus Calmette-Guérin, maintenance, and induction. All randomized controlled trials and meta-analyses, including those based on indirect comparisons, were evaluated. EVIDENCE SYNTHESIS: Seven randomized studies compared induction BCG plus maintenance to induction alone, with or without retreatment with BCG on recurrence. All but one of these studies were underpowered and the largest study used a broad, composite end point: worsening-free survival. Seven meta-analyses have been conducted, three of which included data from observational cohort studies. They demonstrated the benefit of maintenance BCG to reduce disease recurrence and delay progression compared to various control groups; however, the analyses were based on suboptimal data. Although there is new evidence that 1 yr of maintenance BCG is sufficient treatment in intermediate-risk patients, the optimal duration of BCG maintenance remains unknown. A new randomized trial is proposed, which includes induction BCG with retreatment on recurrence as a control arm, to study this question. CONCLUSIONS: The optimal duration of BCG treatment in patients with NMIBC remains unknown and should be the subject of further studies. We recommend that in addition to 3 yr of maintenance BCG, guideline panels also include 1 yr of therapy and induction BCG with retreatment on recurrence as a possible treatment options for patients with NMIBC, albeit with a lower level of evidence and grade of recommendation.

15 Review Repeated white light transurethral resection of the bladder in nonmuscle-invasive urothelial bladder cancers: systematic review and meta-analysis. 2011

Vianello, Alberto / Costantini, Elisabetta / Del Zingaro, Michele / Bini, Vittorio / Herr, Harry W / Porena, Massimo. ·Department of Medical-Surgical Specialties and Public Health, Urology Section, University of Perugia, Santa Maria della Misericordia Hospital, Sant'Andrea delle Fratte, Perugia, Italy. alberto.vianello@unipg.it ·J Endourol · Pubmed #21936670.

ABSTRACT: BACKGROUND AND PURPOSE: Transurethral resection of the bladder (TURB), the first step in treatment of patients with urothelial bladder cancers, is limited by technicalities, surgeon skill, and random chance. When high-risk superficial diseases are discovered, a repeated TURB is indicated. We reviewed current literature and performed a meta-analysis of the role of repeated TURB in the management of nonmuscle-invasive bladder cancers. METHODS: PubMed, MEDLINE, ISI Web of Knowledge, EBSCO, EMBASE, and Biomed Central databases were searched for reports in English from 1980 to June 2010. The end point was prevalence of persistent urothelial bladder cancer of any stage and grade at repeated TURB, assessed separately for T(a) and T(1) lesions at TURB. Persistence was presence at repeated TURB of same or lower stage cancer as at TURB; upstaging was presence of higher stage. RESULTS: There were 2327 original articles and 562 reviews retrieved. Data from 15 studies were pooled and analyzed. Prevalence of T(1) was reported in all and of T(a) in 8. Persistence rate prevalence at repeated TURB was 0.39 (95% confidence interval [CI]=0.26 to 0.54) for T(a) and 0.47 (95% CI=0.41 to 0.53) for T(1). Persistence was 19.4% to 56% and 15.2% to 55%, and upstaging occurred in 0% to 14.3% of T(a) and 0% to 24.4% of T(1) at repeated TURB, respectively. CONCLUSION: High percentages of persistence and upstaging confirm a repeated TURB is needed in patients with high-risk nonmuscle-invasive bladder cancer. Further investigation is encouraged taking risk stratification into consideration to evaluate the role of repeated TURB in low- and mid- risk diseases.

16 Review Role of re-resection in non-muscle-invasive bladder cancer. 2011

Herr, Harry W. ·Memorial Sloan-Kettering Cancer Center, New York, USA. herrh@MSKCC.ORG ·ScientificWorldJournal · Pubmed #21298219.

ABSTRACT: Restaging, or second transurethral resection (TUR), is essential to successful management of high-risk, non-muscle-invasive bladder cancer. Here we review the relevant literature documenting the role of restaging TUR. Cohort and randomized studies show that restaging TUR detects more tumors than initial TUR, improves clinical staging, and reduces the frequency of early tumor recurrences. Our conclusions show thatrestaging TUR improves the outcomes of high-risk,non-muscle-invasive bladder neoplasms.

17 Review Maximizing cure for muscle-invasive bladder cancer: integration of surgery and chemotherapy. 2011

Feifer, Andrew H / Taylor, Jennifer M / Tarin, Tatum V / Herr, Harry W. ·Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. ·Eur Urol · Pubmed #21257257.

ABSTRACT: CONTEXT: The optimal treatment strategy for muscle-invasive bladder cancer remains controversial. OBJECTIVE: To determine optimal combination of chemotherapy and surgery aimed at preserving survival of patients with locally advanced bladder cancer. EVIDENCE ACQUISITION: We performed a critical review of the published abstract and presentation literature on combined modality therapy for muscle-invasive bladder cancer. We emphasized articles of the highest scientific level, combining radical cystectomy and perioperative chemotherapy with curative intent to affect overall and disease-specific survival. EVIDENCE SYNTHESIS: Locally invasive, regional, and occult micrometastases at the time of radical cystectomy lead to both distant and local failure, causing bladder cancer deaths. Neoadjuvant and adjuvant chemotherapy regimens have been evaluated, as well as the quality of cystectomy and pelvic lymph node dissection. CONCLUSIONS: Prospective, randomized clinical trials argue strongly for neoadjuvant cisplatin-based chemotherapy followed by high-quality cystectomy performed by an experienced surgeon operating in a high-volume center. Adjuvant chemotherapy after surgery is also effective when therapeutic doses can be given in a timely fashion. Both contribute to improved overall survival; however, many patients receive only one or none of these options, and the barriers to receiving optimal, combined, systemic therapy and surgery remain to be defined. An aging, comorbid, and often unfit population increasingly affected by bladder cancer poses significant challenges in management of individual patients.

18 Guideline NCCN Guidelines Insights: Bladder Cancer, Version 2.2016. 2016

Clark, Peter E / Spiess, Philippe E / Agarwal, Neeraj / Bangs, Rick / Boorjian, Stephen A / Buyyounouski, Mark K / Efstathiou, Jason A / Flaig, Thomas W / Friedlander, Terence / Greenberg, Richard E / Guru, Khurshid A / Hahn, Noah / Herr, Harry W / Hoimes, Christopher / Inman, Brant A / Kader, A Karim / Kibel, Adam S / Kuzel, Timothy M / Lele, Subodh M / Meeks, Joshua J / Michalski, Jeff / Montgomery, Jeffrey S / Pagliaro, Lance C / Pal, Sumanta K / Patterson, Anthony / Petrylak, Daniel / Plimack, Elizabeth R / Pohar, Kamal S / Porter, Michael P / Sexton, Wade J / Siefker-Radtke, Arlene O / Sonpavde, Guru / Tward, Jonathan / Wile, Geoffrey / Dwyer, Mary A / Smith, Courtney. ·From Vanderbilt-Ingram Cancer Center; Moffitt Cancer Center; Huntsman Cancer Institute at the University of Utah; Patient Advocate; Mayo Clinic Cancer Center; Stanford Cancer Institute; Massachusetts General Hospital Cancer Center; University of Colorado Cancer Center; UCSF Helen Diller Family Comprehensive Cancer Center; Fox Chase Cancer Center; Roswell Park Cancer Institute; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; Memorial Sloan Kettering Cancer Center; Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute; Duke Cancer Institute; UC San Diego Moores Cancer Center; Dana-Farber/Brigham and Women's Cancer Center; Robert H. Lurie Comprehensive Cancer Center of Northwestern University; Fred & Pamela Buffett Cancer Center; Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine; University of Michigan Comprehensive Cancer Center; City of Hope Comprehensive Cancer Center; St. Jude Children's Research Hospital/The University of Tennessee Health Science Center; Yale Cancer Center/Smilow Cancer Hospital; The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute; University of Washington/Seattle Cancer Care Alliance; The University of Texas MD Anderson Cancer Center; University of Alabama at Birmingham Comprehensive Cancer Center; and National Comprehensive Cancer Network. ·J Natl Compr Canc Netw · Pubmed #27697976.

ABSTRACT: These NCCN Guidelines Insights discuss the major recent updates to the NCCN Guidelines for Bladder Cancer based on the review of the evidence in conjunction with the expert opinion of the panel. Recent updates include (1) refining the recommendation of intravesical bacillus Calmette-Guérin, (2) strengthening the recommendations for perioperative systemic chemotherapy, and (3) incorporating immunotherapy into second-line therapy for locally advanced or metastatic disease. These NCCN Guidelines Insights further discuss factors that affect integration of these recommendations into clinical practice.

19 Clinical Trial Multicenter Prospective Phase II Trial of Neoadjuvant Dose-Dense Gemcitabine Plus Cisplatin in Patients With Muscle-Invasive Bladder Cancer. 2018

Iyer, Gopa / Balar, Arjun V / Milowsky, Matthew I / Bochner, Bernard H / Dalbagni, Guido / Donat, S Machele / Herr, Harry W / Huang, William C / Taneja, Samir S / Woods, Michael / Ostrovnaya, Irina / Al-Ahmadie, Hikmat / Arcila, Maria E / Riches, Jamie C / Meier, Andreas / Bourque, Caitlin / Shady, Maha / Won, Helen / Rose, Tracy L / Kim, William Y / Kania, Brooke E / Boyd, Mariel E / Cipolla, Catharine K / Regazzi, Ashley M / Delbeau, Daniela / McCoy, Asia S / Vargas, Hebert Alberto / Berger, Michael F / Solit, David B / Rosenberg, Jonathan E / Bajorin, Dean F. ·Gopa Iyer, Bernard H. Bochner, Guido Dalbagni, S. Machele Donat, Harry W. Herr, Irina Ostrovnaya, Hikmat Al-Ahmadie, Maria E. Arcila, Jamie C. Riches, Andreas Meier, Caitlin Bourque, Maha Shady, Helen Won, Brooke E. Kania, Mariel E. Boyd, Catharine K. Cipolla, Ashley M. Regazzi, Asia S. McCoy, Hebert Alberto Vargas, Michael F. Berger, David B. Solit, Jonathan E. Rosenberg, and Dean F. Bajorin, Memorial Sloan Kettering Cancer Center · Gopa Iyer, Bernard H. Bochner, Guido Dalbagni, S. Machele Donat, Harry W. Herr, Hikmat Al-Ahmadie, David B. Solit, and Dean F. Bajorin, Weill Cornell Medical College · Arjun V. Balar, William C. Huang, Samir S. Taneja, and Daniela Delbeau, New York University Langone Medical Center, New York, NY · and Matthew I. Milowsky, Michael Woods, Tracy L. Rose, and William Y. Kim, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC. ·J Clin Oncol · Pubmed #29742009.

ABSTRACT: Purpose Neoadjuvant chemotherapy followed by radical cystectomy (RC) is a standard of care for the management of muscle-invasive bladder cancer (MIBC). Dose-dense cisplatin-based regimens have yielded favorable outcomes compared with standard-dose chemotherapy, yet the optimal neoadjuvant regimen remains undefined. We assessed the efficacy and tolerability of six cycles of neoadjuvant dose-dense gemcitabine and cisplatin (ddGC) in patients with MIBC. Patients and Methods In this prospective, multicenter phase II study, patients received ddGC (gemcitabine 2,500 mg/m

20 Clinical Trial Lymph node density for patient counselling about prognosis and for designing clinical trials of adjuvant therapies after radical cystectomy. 2012

Lee, Eugene K / Herr, Harry W / Dickstein, Rian J / Kassouf, Wassim / Munsell, Mark F / Grossman, H Barton / Dinney, Colin P N / Kamat, Ashish M. ·Department of Urology Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. ·BJU Int · Pubmed #22758775.

ABSTRACT: OBJECTIVE: • To develop a clinical tool based on lymph node density (LND) for patient counselling after radical cystectomy and for design of clinical trials of adjuvant therapies after radical cystectomy. PATIENTS AND METHODS: • Using pooled data from two comprehensive cancer centres, we identified patients with lymph node metastases after radical cystectomy who received an adequate lymph node dissection according to existing literature (resection of eight or more nodes). • Only patients who had not received neoadjuvant or adjuvant chemotherapy were included to ensure that prediction models were based on the natural course of the disease. • Thresholds for LND ranging from 5% to 35%, in 5% increments, were used to dichotomize the study population. Within each set of two groups, the Kaplan-Meier product-limit estimator was used to estimate disease-specific survival (DSS) for each group, and Cox proportional hazards regression was used to test the significance of differences in DSS between the group with higher LND and the group with lower LND. • Tables and graphs showing the relationship between LND categories and 2-year and 5-year estimated DSS were created to aid in clinical decision-making. RESULTS: • LND was valuable as a tool for stratifying node-positive patients into different risk groups based on expected survival. • At each LND threshold from 10% to 35%, patients with higher LND had significantly worse DSS than patients with lower LND (P ≤ 0.001). • As expected, DSS in the higher-LND group worsened with each 5% increase in LND threshold: patients with LND > 35% had a 5-year DSS rate of 4%. • Using our data as a tool, multiple cut-offs can be employed to categorize patients into various risk groups with different risk. For example, patients with LND ≤ 10% have an estimated 5-year DSS rate of 61.9%, whereas patients with LND > 15% have an estimated 5-year DSS rate of 19.2%. CONCLUSIONS: • Patients with node-positive bladder cancer have poor outcomes, and survival varies widely according to LND. • Categorical LND should be used to risk-stratify patients for counselling regarding prognosis. • Furthermore, categorical LND should be used as a tool for designing and reporting on clinical trials of adjuvant therapies.

21 Article Trends in Management and Outcomes Among Patients with Urothelial Carcinoma Undergoing Radical Cystectomy from 1995 to 2015: The Memorial Sloan Kettering Experience. 2020

Almassi, Nima / Cha, Eugene K / Vertosick, Emily A / Huang, Chun / Wong, Nathan / Dason, Shawn / McPherson, Victor / Dean, Lucas / Benfante, Nicole / Sjoberg, Daniel D / Rosenberg, Jonathan E / Bajorin, Dean F / Herr, Harry W / Dalbagni, Guido / Bochner, Bernard H. ·Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York. · Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. ·J Urol · Pubmed #32294398.

ABSTRACT: PURPOSE: To evaluate trends in oncologic characteristics and outcomes, as well as perioperative management, among patients undergoing radical cystectomy at Memorial Sloan Kettering from 1995 to 2015. MATERIALS AND METHODS: We retrospectively reviewed our institutional database to analyze changes in disease recurrence probability, cancer-specific and all-cause mortality, incidence of muscle-invasive bladder cancer, use of perioperative chemotherapy, rate of positive soft-tissue surgical margins, and lymph node yield. RESULTS: In 2,740 patients with non-metastatic urothelial carcinoma undergoing radical cystectomy from 1995 to 2015, the 5-year probability of disease recurrence decreased from a peak of 42% in 1997 to 34% in 2013 (p=0.045), while 5-year probability of cancer-specific mortality likewise declined from 36% in 1997 to 24% in 2013 (p=0.009). Incidence of non-muscle-invasive disease before radical cystectomy did not change, comprising 30%-35% of patients across the study period. Use of neoadjuvant chemotherapy rose significantly: 57% of patients with muscle-invasive bladder cancer from 2010 to 2015 received it. We observed a corresponding rise in complete pathologic response (pT0) at radical cystectomy, as well as decreasing positive soft-tissue surgical margins (10% to 2.5%) and rising lymph node yield (7 to 24) from 1995 to 2015. CONCLUSIONS: Over a 21-year period, outcomes after radical cystectomy at our institution improved significantly, as probability of recurrence and cancer-specific mortality decreased. Increasing utilization of neoadjuvant chemotherapy, rising pT0 rates, decreased positive soft-tissue surgical margins, and increasing lymph node yields likely contributed, suggesting that optimized surgical and perioperative care led to improved cancer outcomes in patients undergoing radical cystectomy.

22 Article Neoadjuvant Gemcitabine-Cisplatin Plus Radical Cystectomy-Pelvic Lymph Node Dissection for Muscle-invasive Bladder Cancer: A 12-year Experience. 2020

Iyer, Gopa / Tully, Christopher M / Zabor, Emily C / Bochner, Bernard H / Dalbagni, Guido / Herr, Harry W / Donat, S Machelle / Russo, Paul / Ostrovnaya, Irina / Regazzi, Ashley M / Milowsky, Matthew I / Rosenberg, Jonathan E / Bajorin, Dean F. ·Department of Medicine, Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New York, NY. Electronic address: iyerg@mskcc.org. · Department of Medicine, Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New York, NY. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY. · Department of Surgery, Urology Service, Memorial Sloan Kettering Cancer Center, New York, NY. · Department of Medicine, Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY. · Division of Hematology/Oncology, Department of Medicine, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC. ·Clin Genitourin Cancer · Pubmed #32273235.

ABSTRACT: INTRODUCTION: The aim of this study was to determine drug delivery/toxicity, and pathologic/surgical outcomes of patients with muscle-invasive bladder cancer (MIBC) receiving neoadjuvant gemcitabine-cisplatin (GC) plus radical cystectomy-pelvic lymph node dissection (RC-PLND). PATIENTS AND METHODS: Chemotherapy and surgical/pathologic outcomes were retrospectively analyzed with 5-year survival follow-up at a referral center. Post-neoadjuvant chemotherapy (NAC) pathologic endpoints included complete response (pT0N0), residual non-MIBC (pTa/Tis/T1N0), and ≥ MIBC (≥ pT2 and/or N+). Associations of pathologic/surgical findings with overall survival (OS), disease-free survival (DFS), and surgical management with RC-PLND were analyzed (Cox regression). RESULTS: Clinical T2a-T4aN0M0 MIBC patients (n = 154) from January 2000-October 2012 received GC plus RC-PLND. Patients (n = 117; 76%) received GC × 4 and 136 (88%) GC × 3. Five-year OS was 61% (95% confidence interval [CI], 53-71). Median number of resected lymph nodes (LNs) was 19. Down-staging was observed as follows: pT0N0: 21%; pTa/Tis/T1N0: 25%, with similar 5-year OS (85% and 89%, respectively). Five-year OS for < pT2 versus ≥ pT2 residual disease was 87% (95% CI, 78%-98%) versus 38% (95% CI, 27%-53%); P < .001. Post-NAC stage ≥ pT2 (HR, 6.79; 95% CI, 2.63-17.53; P < .001), positive LN (HR, 3.64; 95% CI, 1.84-7.19; P < .001), and positive margins (HR, 4.15; 95% CI, 1.68-10.25; P = .002) were associated with increased risk of all-cause death (multivariable analysis). An HR of 0.97 (95% CI, 0.94-1.00) was observed for each additional node removed, but this effect was not statistically significant (P = .056). CONCLUSIONS: Neoadjuvant GC achieves meaningful pathologic responses. Patients with ≥ pT2 residual disease, positive margins, or positive LN post-chemotherapy have inferior survival.

23 Article Propensity-matched analysis of patient-reported outcomes for neoadjuvant chemotherapy prior to radical cystectomy. 2019

Feuerstein, Michael A / Goldstein, Leah / Reaves, Brieyona / Sun, Arony / Goltzman, Michael / Morganstern, Bradley A / Shabsigh, Ahmad / Bajorin, Dean F / Rosenberg, Jonathan E / Donat, S Machele / Herr, Harry W / Laudone, Vincent P / Atkinson, Thomas M / Li, Yuelin / Dalbagni, Guido / Rapkin, Bruce / Bochner, Bernard H. ·Department of Surgery-Urology Service, Memorial Sloan Kettering Cancer Center, 170 E. 77th St, New York, NY, 10075, USA. mfeuerste1@northwell.edu. · Department of Surgery-Urology Service, Memorial Sloan Kettering Cancer Center, 170 E. 77th St, New York, NY, 10075, USA. · Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA. ·World J Urol · Pubmed #30798382.

ABSTRACT: PURPOSE: To evaluate patient-reported outcomes (PROs) for bladder cancer patients undergoing neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) using longitudinal data and propensity-matched scoring analyses. METHODS: 155 patients with muscle-invasive bladder cancer scheduled for RC completed the European Organization for Research and Treatment of Cancer questionnaires, EORTC QLQ-C30, EORTC QLQ-BLM30, Fear of Recurrence Scale, Mental Health Inventory and Satisfaction with Life Scale within 4 weeks of surgery. A propensity-matched analysis was performed comparing pre-surgery PROs among 101 patients who completed NAC versus 54 patients who did not receive NAC. We also compared PROs pre- and post-chemotherapy for 16 patients who had data available for both time points. RESULTS: In propensity-matched analysis, NAC-treated patients reported better emotional and sexual function, mental health, urinary function and fewer financial concerns compared to those that did not receive NAC. Longitudinal analysis showed increases in fatigue, nausea and appetite loss following chemotherapy. CONCLUSION: Propensity-matched analysis did not demonstrate a negative effect of NAC on PRO. Several positive associations of NAC were found in the propensity-matched analysis, possibly due to other confounding differences between the two groups or actual clinical benefit. Longitudinal analysis of a small number of patients found small to modest detrimental effects from NAC similar to toxicities previously reported. Our preliminary findings, along with known survival and toxicity data, should be considered in decision-making for NAC.

24 Article Genomic Differences Between "Primary" and "Secondary" Muscle-invasive Bladder Cancer as a Basis for Disparate Outcomes to Cisplatin-based Neoadjuvant Chemotherapy. 2019

Pietzak, Eugene J / Zabor, Emily C / Bagrodia, Aditya / Armenia, Joshua / Hu, Wenhuo / Zehir, Ahmet / Funt, Samuel / Audenet, Francois / Barron, David / Maamouri, Noelia / Li, Qiang / Teo, Min Yuen / Arcila, Maria E / Berger, Michael F / Schultz, Nikolaus / Dalbagni, Guido / Herr, Harry W / Bajorin, Dean F / Rosenberg, Jonathan E / Al-Ahmadie, Hikmat / Bochner, Bernard H / Solit, David B / Iyer, Gopa. ·Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: pietzake@MSKCC.org. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. ·Eur Urol · Pubmed #30290956.

ABSTRACT: BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is the standard of care for patients with muscle-invasive bladder cancer (MIBC). It is unknown whether this treatment strategy is appropriate for patients who progress to MIBC after treatment for prior noninvasive disease (secondary MIBC). OBJECTIVE: To determine whether clinical and genomic differences exist between primary and secondary MIBC treated with NAC and RC. DESIGN, SETTING, AND PARTICIPANTS: Clinicopathologic outcomes were compared between 245 patients with clinical T2-4aN0M0-stage primary MIBC and 43 with secondary MIBC treated with NAC and RC at Memorial Sloan Kettering Cancer Center (MSKCC) from 2001 to 2015. Genomic differences were assessed in a retrospective cohort of 385 prechemotherapy specimens sequenced by whole-exome or targeted exon capture by the Cancer Genome Atlas or at MSKCC. Findings were confirmed in an independent validation cohort of 94 MIBC patients undergoing prospective targeted exon sequencing at MSKCC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Pathologic response rates, recurrence-free survival (RFS), bladder cancer-specific survival (CSS), and overall survival (OS) were measured. Differences in somatic genomic alteration rates were compared using Fisher's exact test and the Benjamini-Hochberg false discovery rate method. RESULTS AND LIMITATIONS: Patients with secondary MIBC had lower pathologic response rates following NAC than those with primary MIBC (univariable: 26% vs 45%, multivariable: odds ratio=0.4 [95% confidence interval=0.18-0.84] p=0.02) and significantly worse RFS, CSS, and OS. Patients with secondary MIBC treated with NAC had worse CSS compared with cystectomy alone (p=0.002). In a separate genomic analysis, we detected significantly more likely deleterious somatic ERCC2 missense mutations in primary MIBC tumors in both the discovery (10.9% [36/330] vs 1.8% [1/55], p=0.04) and the validation (15.7% [12/70] vs 0% [0/24], p=0.03) cohort. CONCLUSIONS: Patients with secondary MIBC treated with NAC had worse clinical outcomes than similarly treated patients with primary MIBC. ERCC2 mutations predicted to result in increased cisplatin sensitivity were enriched in primary versus secondary MIBC. Prospective validation is still needed, but given the lack of clinical benefit with cisplatin-based NAC in patients with secondary MIBC, upfront RC or enrollment in clinical trials should be considered. PATIENT SUMMARY: A retrospective cohort study of patients with "primary" and "secondary" muscle-invasive bladder cancer (MIBC) treated with chemotherapy before surgical removal of the bladder identified lower response rates and shorter survival in patients with secondary MIBC. Tumor genetic sequencing of separate discovery and validation cohorts revealed that chemotherapy-sensitizing DNA damage repair gene mutations occur predominantly in primary MIBC tumors and may underlie the greater sensitivity of primary MIBC to chemotherapy. Prospective validation is still needed, but patients with secondary MIBC may derive greater benefit from upfront surgery or enrollment in clinical trials rather than from standard chemotherapy.

25 Article The Impact of Plasmacytoid Variant Histology on the Survival of Patients with Urothelial Carcinoma of Bladder after Radical Cystectomy. 2019

Li, Qiang / Assel, Melissa / Benfante, Nicole E / Pietzak, Eugene J / Herr, Harry W / Donat, Machele / Cha, Eugene K / Donahue, Timothy F / Bochner, Bernard H / Dalbagni, Guido. ·Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Epidemiology-Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: dalbagng@mskcc.org. ·Eur Urol Focus · Pubmed #28753857.

ABSTRACT: BACKGROUND: The clinical significance of the plasmacytoid variant (PCV) in urothelial carcinoma (UC) is currently lacking. OBJECTIVE: To compare clinical outcomes of patients with any PCV with that of patients with pure UC treated with radical cystectomy (RC). DESIGN, SETTING, AND PARTICIPANTS: We identified 98 patients who had pathologically confirmed PCV UC and 1312 patients with pure UC and no variant history who underwent RC at our institution between 1995 and 2014. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Univariable and multivariable Cox regression and Cox proportional hazards regression to determine if PCV was associated with overall survival (OS). RESULTS AND LIMITATIONS: Patients with PCV UC were more likely to have advanced tumor stage (p=0.001), positive lymph nodes (p=0.038), and receive neoadjuvant chemotherapy than those with pure UC (46% vs 22%, p<0.0001). The rate of positive soft tissue surgical margins was over five times greater in the PCV UC group compared with the pure UC group (21% vs 4.1%, respectively, p<0.0001). Median OS for the pure UC versus the PCV patients were 8 yr and 3.8 yr, respectively. On univariable analysis, PCV was associated with an increased risk of overall mortality (hazard ratio=1.34, 95% confidence interval: 1.02-1.78, p=0.039). However, on multivariable analysis adjusted for age, sex, neoadjuvant chemotherapy received, lymph node status, pathologic stage, and soft margin status, the association between PCV and OS was no longer significant (hazard ratio=1.06, 95% confidence interval: 0.78, 1.43, p=0.7). This retrospective study is limited by the lack of pathological reanalysis, and the impact of other concurrent mixed histology cannot be determined in this study. CONCLUSIONS: Patients with PCV features have a higher disease burden at RC compared with those with pure UC. However, PCV was not an independent predictor of survival after RC on multivariable analysis, suggesting that PCV histology should not be used as an independent prognostic factor. PATIENT SUMMARY: Plasmacytoid urothelial carcinoma is a rare and aggressive form of bladder cancer. Patients with plasmacytoid urothelial carcinoma had worse adverse pathologic features, but this was not associated with worse overall mortality when compared with patients with pure urothelial carcinoma.

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