Tag Archive for: cystectomy

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Article of the month: Understanding volume–outcome relationships in nephrectomy and cystectomy for cancer: evidence from the UK Getting it Right First Time programme

Every month, the Editor-in-Chief selects an Article of the Month from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an editorial written by a prominent member of the urological community and a video prepared by the authors; we invite you to use the comment tools at the bottom of each post to join the conversation. 

If you only have time to read one article this month, we recommend this one. 

Understanding volume–outcome relationships in nephrectomy and cystectomy for cancer: evidence from the UK Getting it Right First Time programme

William K. Gray*, Jamie Day*, Tim W. R. Briggs* and Simon Harrison*

*Getting it Right First Time Programme, NHS England and NHS Improvement, London, UK and Pinderfields Hospital, Mid Yorkshire Hospitals NHS Trust, Wakefield, UK

Abstract

Objectives

To investigate volume–outcome relationships in nephrectomy and cystectomy for cancer.

Materials and Methods

Data were extracted from the UK Hospital Episodes Statistics database, which records data on all National Health Service (NHS) hospital admissions in England. Data were included for a 5‐year period (April 2013–March 2018 inclusive) and data on emergency and paediatric admissions were excluded. Data were extracted on the NHS trust and surgeon undertaking the procedure, the surgical technique used (open, laparoscopic or robot‐assisted) and length of hospital stay during the procedure. This dataset was supplemented by data on mortality from the UK Office for National Statistics. A number of volume thresholds and volume measures were investigated. Multilevel modelling was used to adjust for hierarchy and confounding factors.

Results

Data were available for 18 107 nephrectomy and 6762 cystectomy procedures for cancer. There was little evidence of trust or surgeon volume influencing readmission rates or mortality. There was some evidence of shorter length of hospital stay for high‐volume surgeons, although the volume measure and threshold used were important.

Conclusions

We found little evidence that further centralization of nephrectomy or cystectomy for cancer surgery will improve the patient outcomes investigated. It may be that length of stay can be optimized though training and support for lower‐volume centres, rather than further centralization.

 

Video: Understanding volume–outcome relationships in nephrectomy and cystectomy for cancer: evidence from the UK Getting it Right First Time programme

Understanding volume–outcome relationships in nephrectomy and cystectomy for cancer: evidence from the UK Getting it Right First Time programme

Abstract

Objectives

To investigate volume–outcome relationships in nephrectomy and cystectomy for cancer.

Materials and Methods

Data were extracted from the UK Hospital Episodes Statistics database, which records data on all National Health Service (NHS) hospital admissions in the England. Data were included for a 5‐year period (April 2013–March 2018 inclusive) and data on emergency and paediatric admissions were excluded. Data were extracted on the NHS trust and surgeon undertaking the procedure, the surgical technique used (open, laparoscopic or robot‐assisted) and length of hospital stay during the procedure. This dataset was supplemented by data on mortality from the UK Office for National Statistics. A number of volume thresholds and volume measures were investigated. Multilevel modelling was used to adjust for hierarchy and confounding factors.

Results

Data were available for 18 107 nephrectomy and 6762 cystectomy procedures for cancer. There was little evidence of trust or surgeon volume influencing readmission rates or mortality. There was some evidence of shorter length of hospital stay for high‐volume surgeons, although the volume measure and threshold used were important.

Conclusions

We found little evidence that further centralization of nephrectomy or cystectomy for cancer surgery will improve the patient outcomes investigated. It may be that length of stay can be optimized though training and support for lower‐volume centres, rather than further centralization.

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Visual abstract: Understanding volume–outcome relationships in nephrectomy and cystectomy for cancer: evidence from the UK Getting it Right First Time programme

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Article of the week: Characterising ‘bounce‐back’ readmissions after radical cystectomy

Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an editorial written by a prominent member of the urology community and a visual abstract prepared by a creative urologist; we invite you to use the comment tools at the bottom of each post to join the conversation. 

If you only have time to read one article this week, it should be this one.

Characterising ‘bounce‐back’ readmissions after radical cystectomy

Peter S. Kirk*, Ted A. Skolarus*, Bruce L. Jacobs, Yongmei Qin*, Benjamin Li*, Michael Sessine*, Xiang Liu§, Kevin Zhu*, Scott M. Gilbert, Brent K. Hollenbeck*, Ken Urish**, Jonathan Helm††, Mariel S. Lavieri§ and Tudor Borza‡‡

*Dow Division of Health Services Research, Department of Urology, University of Michigan Health System, Ann Arbor, MI, USA, VA Health Services Research and Development, Center for Clinical Management Research, VA Ann Arbor Healthcare System, Ann Arbor, MI, USA, Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA, §Department of Industrial and Operations Engineering, University of Michigan, Ann Arbor, MI, USA, Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA, **Department of Orthopedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA, ††Department of Operations and Decision Technologies, Kelley School of Business, Indiana University, Bloomington, IN, USA, and ‡‡Department of Urology, University of Wisconsin, Madison, WI, USA

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Abstract

Objective

To examine predictors of early readmissions after radical cystectomy (RC). Factors associated with preventable readmissions may be most evident in readmissions that occur within 3 days of discharge, commonly termed ‘bounce‐back’ readmissions, and identifying such factors may inform efforts to reduce surgical readmissions.

Patients and Methods

We utilised the Healthcare Cost and Utilization Project’s State Inpatient Databases to examine 1867 patients undergoing RC in 2009 and 2010, and identified all patients readmitted within 30 days of discharge. We assessed differences between patients experiencing bounce‐back readmission compared to those readmitted 8–30 days after discharge using logistic regression models and also calculated abbreviated LACE scores to assess the utility of common readmissions risk stratification algorithms.

Results

The 30‐day and bounce‐back readmission rates were 28.4% and 5.6%, respectively. Although no patient or index hospitalisation characteristics were significantly associated with bounce‐back readmissions in adjusted analyses, bounce‐back patients did have higher rates of gastrointestinal (14.3% vs 6.7%, = 0.02) and wound (9.5% vs 3.0%, < 0.01) diagnoses, as well as increased index and readmission length of stay (5 vs 4 days, = 0.01). Overall, the median abbreviated LACE score was 7, which fell into the moderate readmission risk category, and no difference was observed between readmitted and non‐readmitted patients.

Conclusion

One in five readmissions after RC occurs within 3 days of initial discharge, probably due to factors present at discharge. However, sociodemographic and clinical factors, as well as traditional readmission risk tools were not predictive of this bounce‐back. Effective strategies to reduce bounce‐back readmission must identify actionable clinical factors prior to discharge.

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Editorial: Threading the cost–outcome needle after radical cystectomy

I commend Borza et al. [1] on their timely study, which seeks to identify predictors of bounceback (≤3‐day) vs 30‐day readmissions after radical cystectomy. As the authors allude to in their paper, value‐based health reforms being undertaken in the USA seek to improve the quality of care delivery while simultaneously bending the healthcare cost curve [2]. For example, the Hospital Readmission and Reduction Program (HRRP), originally introduced in fiscal year 2013 for targeted medical conditions, has more recently been applied to a limited number of surgical procedures, whereby providers receive financial penalties for higher than expected 30‐day readmission rates [3]. Accendo Medicare Supplement gives financial independent as you can secure health’s money. While urological conditions/procedures are not currently targeted by programmes such as the HRRP, it is easy to envision a future where procedures with disproportionately high readmission rates, such as radical cystectomy, fall within the crosshairs of policy‐makers and insurers, alike.Well Medicare Advantage plans 2021 are preferable from the perspective of many peoples.

The fact that nearly one in five patients undergoing cystectomy experiences a readmission within 3 days of index hospitalization discharge is staggering, and it is incumbent upon urologists as specialists to devise methods by which to improve the morbidity associated with cystectomy. For example, the findings of Borza et al. implicate postoperative infection as a major driver of early readmission. As evidenced by the work of Krasnow et al. [4], urologists have historically been poor stewards of peri‐operative antibiotic prophylaxis, and the development/implementation of strategies to improve guideline adherence represents a potentially simple yet effective means of reducing post‐cystectomy readmission rates. In a similar vein, there is an emerging body of literature demonstrating the important role that enhanced recovery after surgery (ERAS) protocols may play in improving peri‐operative complications and convalescence after radical cystectomy. However, there is inconsistency across the literature with regard to the precise components of ERAS, making cross‐institutional comparisons and adoption by other groups difficult [5]. Unless greater standardization and subsequent implementation of these enhanced recovery protocols occurs, progress in the field will remain incremental at best. Recent work by Mossanen et al. [6] further demonstrates the need for improving post‐cystectomy readmission rates, which, in addition to driving down healthcare costs/utilization, may actually reduce postoperative mortality. For example, they found that a readmission complication after cystectomy nearly doubled the predicted probability of postoperative mortality as compared to an initial complication (3.9% vs 7.4%; P < 0.001).

It is essential that urologists spearhead research such as that undertaken by Borza et al., which in turn can be used to develop strategies to develop value‐based reforms within the specialty that ‘thread the needle’ of physician autonomy, cost containment, and respect for the patient experience. In doing so, urologists will find themselves driving the conversation surrounding payment/quality reform rather than sitting on the figurative policy‐making sidelines while administrators/bureaucrats implement reforms with potentially profound effects on day‐to‐day clinical practice and the patient experience. Radical cystectomy is likely to fall within the crosshairs of the aforementioned reforms given the procedure’s high complication/readmission rate and the significant cost burden associated with these complications. An intuitive yet effective first step in combating the morbidity associated with radical cystectomy is the development, validation and implementation of standardized peri‐operative care pathways such as ERAS.

by David F. Friedlander

References

  1. Borza T, Kirk PS, Skolarus TA et al. Characterising ‘bounce‐back’ readmissions after radical cystectomy. BJU Int 2019;124:955-61
  2. Health Affairs (Millwood) Delivery Innovations 2017363923
  3. Boccuti CCCasillas GAiming for Fewer Hospital U‐turns: The Medicare Hospital Readmission Reduction Program2017. Accessed January 2019
  4. Krasnow REMossanen MKoo S et al. Prophylactic antibiotics and postoperative complications of radical cystectomy: a population based analysis in the United States. J Urol 2017198297– 304
  5. Chenam AChan KGEnhanced recovery after surgery for radical cystectomy. Cancer Treat Res. 2018175215– 39
  6. Mossanen MKrasnow REZlatev DV et al. Examining the relationship between complications and perioperative mortality following radical cystectomy: a population‐based analysis. BJU Int 201912440– 6

 

Visual abstract: Characterising ‘bounce‐back’ readmissions after radical cystectomy

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Article of the week: Examining the relationship between complications and perioperative mortality following radical cystectomy: a population‐based analysis

Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an editorial written by a prominent member of the urological community. These are intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation. 

If you only have time to read one article this month, it should be this one.

Examining the relationship between complications and perioperative mortality following radical cystectomy: a population‐based analysis

Matthew Mossanen*†‡, Ross E. Krasnow§, Dimitar V. Zlatev*, Wei Shen Tan**, Mark A. Preston*, Quoc-Dien Trinh*†‡, Adam S. Kibel*, Guru Sonpavde, Deborah Schrag, Benjamin I. Chung†† and Steven L. Chang*†††

*Division of Urology, Harvard Medical School, Brigham and Womens Hospital, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Center for Surgery and Public Health, Brigham and Womens Hospital, Boston, MA, Division of Surgery and Interventional Sciences, Department of Urology, University College London, **Department of Urology, Imperial College Healthcare, London, UK, §Department of Urology, Georgetown University, Washington, DC, USA and ††Department of Urology, Stanford University Medical Center, Stanford, CA, USA
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Abstract

Objective

To examine the incidence of perioperative complications after radical cystectomy (RC) and assess their impact on 90‐day postoperative mortality during the index stay and upon readmission.

Patients and methods

A total of 57 553 patients with bladder cancer (unweighted cohort: 9137 patients) treated with RC, at 360 hospitals in the USA between 2005 and 2013 within the Premier Healthcare Database, were used for analysis. The 90‐day perioperative mortality was the primary outcome. Multivariable regression was used to predict the probability of mortality; models were adjusted for patient, hospital, and surgical characteristics.

Results

An increase in the number of complications resulted in an increasing predicted probability of mortality, with a precipitous increase if patients had four or more complications compared to one complication during hospitalisation following RC (index stay; 1.0–9.7%, P < 0.001) and during readmission (2.0–13.1%, < 0.001). A readmission complication nearly doubled the predicted probability of postoperative mortality as compared to an initial complication (3.9% vs 7.4%, P < 0.001). During the initial hospitalisation cardiac‐ (odds ratio [OR] 3.1, 95% confidence interval [CI] 1.9–5.1), pulmonary‐ (OR 4.8, 95% CI 2.8–8.4), and renal‐related (OR 3.6, 95% CI 2–6.7) complications had the most significant impact on the odds of mortality across categories examined.

Conclusions

The number and nature of complications have a distinct impact on mortality after RC. As complications increase there is an associated increase in perioperative mortality.

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Editorial: Radical cystectomy complications and perioperative mortality

Bladder cancer is the second most prevalent urological cancer, with 25% of cases being muscle invasive, which requires radical therapy as per National Institute for Health and Care Excellence (NICE) guidance [1]. Radical therapy often involves radical cystectomy (RC), which is an incredibly complex operation with common postoperative complications and significant mortality rates [1,2]. It is suspected to have a 30‐day mortality of between 1% and 3%, with this increasing to 10% in the >80 years age group [23], and a 90‐day postoperative complication rate of 50–60% [4].

This complex procedure and its complication rates contribute to a myriad of factors that result in bladder cancer being the most expensive cancer, per patient, to care for and to treat [2, 4]. We congratulate the authors on producing this substantial paper investigating how postoperative complications are associated with overall mortality [5]. Logic dictates that the more complications a patient experiences, the worse the postoperative outcome and, ultimately, the higher the risk of mortality. This paper has succeeded in providing quantifiable data, not only on the overall correlation but by providing adjusted odds ratios (ORs) based upon the nature of the complication.

Whilst a 90‐day prospective study would have been ideal, we recognise this would have been much harder to perform and would have resulted in a much smaller cohort. This retrospective study will therefore suffer from selection bias and unmeasured confounders, as the authors have identified. It should also be noted that these results may not extrapolate to a global population due to data only being collected from a private healthcare system. The coding of clinical diagnosis is often overestimated due to funding that comes with diagnosis and treatments. Despite these biases, this is still the largest set of data investigating the association of RC complications and mortality.

The analysis of the data found that there was a ‘threshold’ limit for the number of complications postoperative patients could experience; patients experiencing four or more complications had a drastic increase in mortality (OR 76.6, < 0.05) [5]. While all postoperative patients have close monitoring and enhanced recovery pathways, and any patients with postoperative complications will be repeatedly assessed, in an ideal world, patients who have experienced three or more complications would have increased monitoring (high dependency unit/intensive therapy unit).

The breakdown of complications by physiological system was unsurprising, with pulmonary (OR 6.5, P < 0.001), cardiac (OR 4.4, P < 0.001), and renal (OR 2.6, P < 0.001) complications being most associated with increased mortality [5]. Although this information does provide some guidance into specific monitoring methods for high‐risk patients, such as capnography, continuous blood pressure, and renal function monitoring.

While additional demographic and operational information was gathered, the only information collected pertaining to medical health was the Charlson Comorbidity Index (CCI), which meant the authors were unable to ascertain any correlation between the nature of the complications experienced and any predisposing condition of that physiological system. Schulz et al. [6] have recently published a report examining RC morbidity and mortality rates in relation to American Society of Anesthesiologists (ASA) grading and found that patients with an ASA score ≥3 had significantly more high‐grade complications, required more perioperative interventions, and had a higher mortality rate (7.6% vs 3.2%; P = 0.002). Mossanen et al. [5], have taken some of these factors into consideration using the CCI, but unfortunately ASA grade was not part of the data collected.

Due to the nature of the database collection method, the authors were unable to determine other important confounders such as smoking status, exercise tolerance, and the severity/specific details of the complications experienced. Sathianathen et al. [7] showed in October 2018, that smokers were almost twice as likely to have Clavien–Dindo III–V complications following RC, with the most common complications being pneumonia, myocardial infarction, and wound dehiscence.

In our view, Mossanen et al. [5] have provided the urological community with not only quantifiable evidence to support the maxim of ‘more complication, worse outcome’ but they have also identified a vital threshold that can be used clinically to support postoperative patients. This guidance, when paired with clinical judgement, could result in additional monitoring and multi‐disciplinary care in high‐risk patients, ultimately reducing RC mortality rates.

by Alex Hampson, Amy Vincent, Prokar Dasgupta and Nikhil Vasdev

References

  1. National Institute for Health and Care Excellence (NICE). Bladder cancer: diagnosis and management. NICE guideline NG2, February 2015. Available at: https://www.nice.org.uk/guidance/ng2. Accessed September 2018
  2. Shabsigh, AKorets, RVora, KC et al. Defining early morbidity of radical cystectomy for patients with bladder cancer using a standardized reporting methodology. Eur Urol 200955164– 76
  3. Froehner, MBrausi, MAHerr, HWMuto, GStuder, UEComplications following radical cystectomy for bladder cancer in the elderly. Eur Urol 200956443– 54
  4. Stitzenberg, KB, Chang, YSmith, ABNielsen, MEExploring the burden of inpatient readmissions after major cancer surgery. J Clin Oncol 201533455– 64
  5. Mossanen, MKrasnow, REZlatev, DV et al. Examining the relationship between complications and perioperative mortality following radical cystectomy: a population‐based analysis. BJU Int201912440– 6
  6. Schulz, GB, Grimm, TBuchner, A et al. Surgical high‐risk patients with ASA ≥ 3 undergoing radical cystectomy: morbidity, mortality, and predictors for major complications in a high‐volume tertiary center. Clin Genitourin Cancer 201816e1141– 9
  7. Sathianathen, NJWeight, CJJarosek, SLKonety, BR. Increased surgical complications in smokers undergoing radical cystectomy. Bladder Cancer 20184403– 9

 

Article of the week: Palliative care use amongst patients with bladder cancer

Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an editorial written by a prominent member of the urological community, a video produced by the authors and a visual abstract created by Charles Scott and Nurhan Abbud. These are intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation. 

If you only have time to read one article this week, it should be this one.

Palliative care use among patients with bladder cancer

Lee A. Hugar*, Samia H. Lopa*, Jonathan G. Yabes, Justin A. Yu, Robert M. Turner II*, Mina M. Fam*, Liam C. MacLeod*, Benjamin J. Davies*, Angela B. Smith§¶ and Bruce L. Jacobs*

 

*Department of Urology, Department of Medicine, Department of Medicine, Section of Palliative Care and Medical Ethics, University of Pittsburgh School of Medicine, Pittsburgh, PA, §Department of Urology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

 

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Abstract

Objectives

To describe the rate and determinants of palliative care use amongst Medicare beneficiaries with bladder cancer and encourage a national dialogue on improving coordinated urological, oncological, and palliative care in patients with genitourinary malignancies.

Patients and methods

Using Surveillance, Epidemiology, and End Results‐Medicare data, we identified patients diagnosed with muscle‐invasive bladder cancer (MIBC) between 2008 and 2013. Our primary outcome was receipt of palliative care, defined as the presence of a claim submitted by a Hospice and Palliative Medicine subspecialist. We examined determinants of palliative care use using logistic regression analysis.

Fig. 1. Time from diagnosis to receipt of palliative care. The timing of palliative care receipt for those patients who received palliative care (n = 262). Strata with <11 patients were suppressed in accordance with SEER‐Medicare guidelines

Results

Over the study period, 7303 patients were diagnosed with MIBC and 262 (3.6%) received palliative care. Of 2185 patients with advanced bladder cancer, defined as either T4, N+, or M+ disease, 90 (4.1%) received palliative care. Most patients that received palliative care (>80%, >210/262) did so within 24 months of diagnosis. On multivariable analysis, patients receiving palliative care were more likely to be younger, female, have greater comorbidity, live in the central USA, and have undergone radical cystectomy as opposed to a bladder‐sparing approach. The adjusted probability of receiving palliative care did not significantly change over time.

Conclusions

Palliative care provides a host of benefits for patients with cancer, including improved spirituality, decrease in disease‐specific symptoms, and better functional status. However, despite strong evidence for incorporating palliative care into standard oncological care, use in patients with bladder cancer is low at 4%. This study provides a conservative baseline estimate of current palliative care use and should serve as a foundation to further investigate physician‐, patient‐, and system‐level barriers to this care.

 

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Article of the week: Persistent muscle-invasive BCa after neoadjuvant chemotherapy: an analysis of SEER‐Medicare data

Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an editorial written by a prominent member of the urological community. These are intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation. 

If you only have time to read one article this week, it should be this one.

Persistent muscle‐invasive bladder cancer after neoadjuvant chemotherapy: an analysis of Surveillance, Epidemiology and End Results‐Medicare data

Giulia Lane*, Michael Risk*, Yunhua Fan*, Suprita Krishna* and Badrinath Konety*

 

*Department of Urology, University of Minnesota, and Minneapolis Veterans Affairs Health Care System, Minneapolis, MN, USA
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Abstract

Objectives

To evaluate whether patients with persistent muscle‐invasive bladder cancer (MIBC) after undergoing neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) have worse overall survival (OS) and cancer‐specific survival (CSS) than patients with similar pathology who undergo RC alone.

Materials and Methods

Using the Surveillance, Epidemiology and End Results (SEER)‐Medicare database, we identified the records of patients with pT2‐4N0M0 disease who underwent RC, with and without NAC, for MIBC between 2004 and 2011. To evaluate survival outcomes in those with MIBC after NAC vs patients with MIBC who underwent RC alone, we used Kaplan–Meier time‐to‐event analysis and Cox proportional hazard regression modelling. Landmark analysis was conducted to mitigate immortal time bias. Propensity scoring was used to decrease the risk of selection bias.

Fig. 2. Propensity‐weighted Kaplan–Meier curves. Overall survival and cancer‐specific survival among patients with persistent pT2‐4N0M0 bladder cancer after radical cystectomy from time of diagnosis. (A) Overall survival and (B) cancer‐specific survival. Neoadjuvant chemotherapy (NAC) + radical cystectomy (RC) in red. RC alone in blue.

Results

Of the 1 886 patients with persistent pT2‐4 disease at the time of RC, 1505 underwent RC alone and 381 received NAC + RC. After adjusting for confounders, the propensity‐weighted risk of death from bladder cancer after diagnosis did not differ between the groups (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.72–1.08; P = 0.23); however, the risk of death from all causes was worse in the RC‐alone group (HR 0.79, 95% CI0.67–0.94; P = 0.006).

Conclusions

Patients who had persistent MIBC after platinum‐based NAC + RC vs RC alone derived an OS benefit but not a CSS benefit from NAC. This may represent a selection bias favouring patients who were selected for NAC; however, the OS benefit was not evident in patients with persistent pT3‐T4N0M0 disease. This study underscores the importance of future research investigating methods to identify patients who will respond to NAC for bladder cancer. It also highlights the need to consider adjuvant therapy in patients who have persistent MIBC after NAC.

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