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Article of the week: The World Health Organization 1973 classification system for grade is an important prognosticator in T1 non‐muscle‐invasive 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 accompanying 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.

The World Health Organization 1973 classification system for grade is an important prognosticator in T1 non‐muscle‐invasive bladder cancer

Elisabeth E. Fransen van de Putte*, Judith Bosschieter*, Theo H. van der Kwast§, Simone Bertz, Stefan Denzinger**, Quentin Manach††, Eva M. Compérat‡‡,
Joost L. Boormans§§, Michael A.S. Jewett¶¶, Robert Stoehr, Geert J.L.H. van Leenders§, Jakko A. Nieuwenhuijzen, Alexandre R. Zlotta¶¶***, Kees Hendricksen*,
Morgan Rouprêt††, Wolfgang Otto**, Maximilian Burger**, Arndt Hartmannand Bas W.G. van Rhijn***§§¶¶

*Department of Surgical Oncology (Urology), Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Department of Urology, VU University Medical Centre, Amsterdam, §Department of Pathology, §§Department of Urology, Erasmus MC Cancer Institute, Erasmus MC, Rotterdam, The Netherlands, Department of Pathology, ¶¶Department of Surgical Oncology (Urology), Princess Margaret Cancer Center, University Health Network, ***Department of Urology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada, Department of Pathology, University of Erlangen, Erlangen, **Department of Urology, Caritas St. Josef Medical Centre, University of Regensburg, Regensburg, Germany, ††Academic Department of Urology and ‡‡Department of Pathology, Pitie-Salpétrière Hospital, Assistance-Publique pitaux de Paris, Pierre et Marie Curie Medical School, University Paris, Paris, France

Abstract

Objectives

To compare the prognostic value of the World Health Organization (WHO) 1973 and 2004 classification systems for grade in T1 bladder cancer (T1‐BC), as both are currently recommended in international guidelines.

Patients and Methods

Three uro‐pathologists re‐revised slides of 601 primary (first diagnosis) T1‐BCs, initially managed conservatively (bacille Calmette–Guérin) in four hospitals. Grade was defined according to WHO1973 (Grade 1–3) and WHO2004 (low‐grade [LG] and high‐grade [HG]). This resulted in a lack of Grade 1 tumours, 188 (31%) Grade 2, and 413 (69%) Grade 3 tumours. There were 47 LG (8%) vs 554 (92%) HG tumours. We determined the prognostic value for progression‐free survival (PFS) and cancer‐specific survival (CSS) in Cox‐regression models and corrected for age, sex, multiplicity, size and concomitant carcinoma in situ.

Results

At a median follow‐up of 5.9 years, 148 patients showed progression and 94 died from BC. The WHO1973 Grade 3 was negatively associated with PFS (hazard ratio [HR] 2.1) and CSS (HR 3.4), whilst WHO2004 grade was not prognostic. On multivariable analysis, WHO1973 grade was the only prognostic factor for progression (HR 2.0). Grade 3 tumours (HR 3.0), older age (HR 1.03) and tumour size >3 cm (HR 1.8) were all independently associated with worse CSS.

Conclusion

The WHO1973 classification system for grade has strong prognostic value in T1‐BC, compared to the WHO2004 system. Our present results suggest that WHO1973 grade cannot be replaced by the WHO2004 classification in non‐muscle‐invasive BC guidelines.

 

 

Editorial: Predicting progression in T1 non‐muscle‐invasive bladder cancer: back to histology

Stage pT1 bladder carcinomas (BCs) represent a difficult clinical scenario as they have different outcomes and are associated with a high risk of progression to muscle‐invasive tumours. The optimal therapeutic approach for individual patients in this setting is still unclear: conservative treatment with BCG instillation and intravesical chemotherapy may lead to disease progression and death, while radical cystectomy may represent a mutilating overtreatment for patients with tumours that may have low potential for progression.

The ability to discriminate those patients who will probably progress to carcinoma invading bladder muscle is therefore crucial. Among prognostic factors associated with progression to muscle invasion, tumour grade is one of the most important. In their important paper, van de Putte et al. [1] aimed to compare the prognostic value of the WHO 1973 and 2004 grading systems, the latter being recommended by the AUA guidelines as the most widely accepted in the USA [2], although it has not been proven superior to the other [3].

The authors collected transurethral resections from 601 primary T1 BCs, initially managed conservatively (BCG), from four institutions, and three pathologists reviewed the slides. Importantly, a second transurethral resection was performed if the muscularis propria was absent and/or the initial resection was incomplete. Grade was assigned according to the WHO 1973 (G1–3) and WHO 2004 (low grade [LG] and high grade [HG]) systems. None of the cases was classified as G1. The prognostic value of both grading systems for progression‐free and cancer‐specific survival was then assessed. Notably, the author found WHO1973 G3 to be significantly negatively associated with progression‐free survival and cancer‐specific survival on multivariable analysis, while the WHO 2004 grading system was not. Importantly, intra‐observer variability was assessed in 66 cases and was found to be almost perfect for the WHO 1973 and moderate to substantial for the WHO 2004 system, while inter‐observer variability ranged from moderate to substantial for both systems. One of the reasons for the lack of prognostic potential of the WHO 2004 system, as underscored by the authors, is the fact that the morphological criteria defined in the WHO 2004 system cause an important shift of many cases from the G2 to HG category, rendering it an almost one‐tier system with consequently very few LG tumours. Other studies have assessed the prognostic value of the WHO 1973 and WHO 2004 systems [3] but so far no clear superiority emerged for one system over the other, probably because of relatively low sample sizes.

Other clinical prognostic factors associated with progression to muscle‐invasive tumours include tumour dimension, the presence of multiple lesions, the presence of carcinoma in situ, lymphovascular invasion and level of lamina propria invasion. Regarding the latter prognostic factor, different studies have defined T1 sub‐staging according to invasion above (T1a), within (T1b) or beyond (T1c) the muscularis mucosae and vascular plexus; however, this approach has been found not to be applicable in >40% of cases because of difficulties in identifying the vascular plexus or lack of orientation of the specimens. A more friendly and reproducible method has been proposed by some of the authors of the study, consisting of a categorization of T1 BCs into microinvasive (T1m) and extensively invasive (T1e) tumours, which has been demonstrated to be applicable in 100% of cases and more reproducible [4]. Further study incorporating T1 sub‐staging together with grade may prove very useful.

Different studies have been performed to identify prognostic markers at the molecular level; however, despite huge efforts, no molecular biomarker with prognostic potential is currently suitable for clinical application [5]. Moreover, in six studies that investigated T1 sub‐stage and molecular markers in the same series, T1 sub‐stage showed the highest prognostic value [4]. More recently, subtyping BC into basal‐like and genomically unstable or squamous cell carcinoma‐like tumours has emerged as a promising tool for dividing T1 BCs into low‐ and high‐risk categories [6]; however, such an approach must be combined with the prognostic value of the classic histological variables discussed so far before eventually being integrated into prognostic tools.

In this regard, van de Putte et al. [1] have shown that tumour grade still represents a powerful marker in T1 BC and that the WHO 2004 grading system cannot replace the WHO 1973 system as a prognosticator of T1 BC; therefore, as recommended by the European Association of Urology guidelines, the WHO 1973 grading system categories should always be present in the pathology reports.

 

References

  1. van de Putte EEF, Bosschieter J, van der Kwast TH et al. The World Health Organization 1973 classification system for grade is an important prognosticator in T1 non‐muscle‐invasive bladder cancer. BJU Int 2018; 122: 978–85
  2. Chang SS, Boorjian SA, Chou R et al. Diagnosis and treatment of non‐muscle invasive bladder cancer: AUA/SUO guideline. J Urol 2016; 196: 1021–93
  3. Babjuk M, Bohle A, Burger M et al. EAU guidelines on non‐muscle‐invasive urothelial carcinoma of the bladder: update 2016. Eur Urol 2017; 71: 447–614
  4. van Rhijn BW, Liu L, Vis AN et al. Prognostic value of molecular markers, sub‐stage and European Organisation for the Research and Treatment of Cancer risk scores in primary T1 bladder cancer. BJU Int 2012; 110: 1169–76
  5. Munari E, Chaux A, Maldonado L et al. Cyclin A1 expression predicts progression in pT1 urothelial carcinoma of bladder: a tissue microarray study of 149 patients treated by transurethral resection. Histopathology 2015; 66: 262–9
  6. Patschan O, Sjodahl G, Chebil G et al. A molecular pathologic framework for risk stratification of stage T1 urothelial carcinoma. Eur Urol 2015; 68: 824–32

 

Video: Centralisation of RC for bladder cancer in England

Centralisation of radical cystectomies for bladder cancer in England, a decade on from the ‘Improving Outcomes Guidance’: the case for super centralisation

Read the full article

Abstract

Objective

To analyse the impact of centralisation of radical cystectomy (RC) provision for bladder cancer in England, on postoperative mortality, length of stay (LoS), complications and re-intervention rates, from implementation of centralisation from 2003 until 2014. In 2002, UK policymakers introduced the ‘Improving Outcomes Guidance’ (IOG) for urological cancers after a global cancer surgery commission identified substantial shortcomings in provision of care of RCs. One key recommendation was centralisation of RCs to high-output centres. No study has yet robustly analysed the changes since the introduction of the IOG, to assess a national healthcare system that has mature data on such institutional transformation.

Patients and Methods

RCs performed for bladder cancer in England between 2003/2004 and 2013/2014 were analysed from Hospital Episode Statistics (HES) data. Outcomes including 30-day, 90-day, and 1-year all-cause postoperative mortality; median LoS; complication and re-intervention rates, were calculated. Multivariable statistical analysis was undertaken to describe the relationship between each surgeon and the providers’ annual case volume and mortality.

Results

In all, 15 292 RCs were identified. The percentage of RCs performed in discordance with the IOG guidelines reduced from 65% to 12.4%, corresponding with an improvement in 30-day mortality from 2.7% to 1.5% (P = 0.024). Procedures adhering to the IOG guidelines had better 30-day mortality (2.1% vs 2.9%; P = 0.003) than those that did not, and better 1-year mortality (21.5% vs 25.6%; P < 0.001), LoS (14 vs 16 days; P < 0.001), and re- intervention rates (30.0% vs 33.6%; P < 0.001). Each single extra surgery per centre reduced the odds of death at 30 days by 1.5% (odds ratio [OR] 0.985, 95% confidence interval [CI] 0.977–0.992) and 1% at 1 year (OR 0.990, 95% CI 0.988–0.993), and significantly reduced rates of re-intervention.

Conclusion

Centralisation has been implemented across England since the publication of the IOG guidelines in 2002. The improved outcomes shown, including that a single extra procedure per year per centre can significantly reduce mortality and re-intervention, may serve to offer healthcare planners an evidence base to propose new guidance for further optimisation of surgical provision, and hope for other healthcare systems that such widespread institutional change is achievable and positive.

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Editorial: Examining the role of centralisation of radical cystectomy for bladder cancer

Despite the high risk of postoperative complications and/or death, radical cystectomy (RC) is currently considered as the standard of care for patients with muscle-invasive bladder cancer (MIBC) without clinical evidence of metastases at initial diagnosis. As an alternative, trimodality bladder-sparing therapy with a potentially more favourable toxicity profile has been developed over recent decades, but definitive surgery may provide better cancer control outcomes, especially in fit individuals. Consequently, efforts have been made recently to improve RC quality by introducing new concepts in the perioperative management of patients with MIBC. For example, the implementation of robot-assisted techniques and enhanced recovery protocols may help to reduce surgical stress and facilitate discharge after early rehabilitation. Nonetheless, such valuable interventions are more likely to be delivered at expert centres in MIBC management.

Interestingly, given that surgical experience mostly comes from surgical volume, numerous studies suggest that there is an inverse relationship between hospital as well as surgeon volume and morbidities for major surgeries including RC. Specifically, a recent meta-analysis showed that high-volume hospitals (odds ratio [OR] 0.55, 95% CI: 0.44–0.69; P < 0.001) and surgeons (OR 0.58, 95% CI: 0.46–0.73; P < 0.001) were significantly associated with a lower risk of death after RC [1]. As a result, centralisation of RC at high-output centres has been advocated worldwide to optimise perioperative management of patients with MIBC and improve short-term outcomes.

In this issue of the BJUI, Afshar et al. [2] eloquently show that such a healthcare policy can be effective at the population level. The authors impressively collected perioperative information on >15 000 RC patients from the Hospital Episode Statistics (HES) dataset in England, where the ‘Improving Outcomes Guidance’ (IOG) programme recommends since 2002 that RC should be performed by surgeons operating at least five cases per year at centres carrying out ≥50 procedures per year. Interestingly, they found that the proportion of RC performed in discordance with IOG guidelines decreased from 60.7% in 2003 to 12.4% in 2013. This resulted in a significant improvement in the overall 30-day crude mortality rate, with a reduction from 2.7% to 1.5% over the 11-year period (P = 0.02). After adjusting for available confounding, RC patients in the non-IOG-compliant group were more likely to die at 30 days (OR 1.41, 95% CI: 1.13–1.76) or 1 year (OR 1.31, 95% CI: 1.21–1.43) as compared to those in the IOG-compliant group. When analysing the incremental effect of hospital volume, each extra RC per year reduced the risk of death at 30 days and 1 year by 1.5% (OR 0.985, 95% CI: 0.977–0.992) and 1% (OR 0.990, 95% CI: 0.988–0.993), respectively. Although there was no significant difference in the odds of postoperative complications between the two groups (OR 0.96, 95% CI: 0.88–1.04), the risk of re-intervention was higher in the non-IOG-compliant group (OR 1.20, 95% CI: 1.12–1.30). It is noteworthy that, as observed for the risk of death, each extra RC decreased the risk of re-intervention (OR 0.99, 95% CI: 0.991–0.995). In conclusion, the findings by Afshar et al. [2] suggest that urologists have embraced centralisation of care for RC patients in England and this is likely to have positively affected the short-term outcomes.

Although, as acknowledged by the authors, many limitations related to the administrative nature of the HES dataset (e.g. missing data or coding errors) may have influenced the aforementioned results, other reports from the USA are consistent with this study. Specifically, it has been estimated that up to 40% of the decline in 30-day mortality after RC from 2000 to 2008 was attributable to centralisation of care [3]. In addition, other RC quality criteria, such as adequate pelvic lymph node dissection at the time of surgery, have improved after similar centralisation in the Netherlands between 2006 and 2012 [4]. As such, centralisation of RC offers many undisputable advantages, but given that travel distance to the treating facility may represent an important barrier for patients with MIBC seeking surgical care, concerns have been raised with regards to potential drawbacks, including increased time to definitive surgery. However, a recent report from the USA showed that, although centralisation of RC has led to a decrease overall access to the treating facilities, the process simultaneously improved access to high-volume centres [5]. It is noteworthy that hospital volume standards for centralisation of RC should not be set too high to avoid unreasonable travel burdens on patients with MIBC [6].

To summarise, centralisation of care is arguably the best way to go, to continue improving quality of RC and its associated short-term outcomes in the near future. Despite inherent limitations, virtually all available evidence, including the study by Afshar et al. [2], converge toward the general concept that RC patients should be managed by experienced urologists operating at expert centres with trained surgical teams.

Thomas Seisen 
Department of Urology, Pitie Salpetriere Hospital, Assistance Publique des Hopitaux de Paris, Paris Sorbonne University, Paris, France

 

Read the full article

 

References

 

 

2 Afshar M, Goodfellow H, Jackson-Spence F et al. Centralisation of radical cystectomies for bladder cancer in England, a decade on from the ‘Improving Outcomes Guidance: the case for super centralisation. BJU Int 2018; 121: 21724 166

 

 3 Finks JF, Osborne NH, Birkmeyer JD. Trends in hospital volume and operative mortality for high-risk surgery. N Engl J Med 2011; 364: 212837

 

4 Hermans TJ, Fransen van de Putte EE, Fossion LM et al. Variations in
pelvic lymph node dissection in invasive bladder cancer: a Dutch

 

nationwide population-based study during centralization of care. Urol
Oncol 2016;34:532. e7532.e12

 

5 Casey MF, Wisnivesky J, Le VH et al. The relationship between centralization of care and geographic barriers to cystectomy for bladder cancer. Bladder Cancer 2016; 2: 31927

 

6 Birkmeyer JD, Siewers AE, Marth NJ, Goodman DC. Regionalization of high-risk surgery and implications for patient travel times. JAMA 2003; 290: 27038

 

Article of the Week: Centralisation of RC for bladder cancer in England

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 accompanying editorial written by a prominent member of the urological community. This blog is 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.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video discussing the paper.

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

Centralisation of radical cystectomies for bladder cancer in England, a decade on from the ‘Improving Outcomes Guidance’: the case for super centralisation

Mehran Afshar*, Henry Goodfellow, Francesca Jackson-Spence, Felicity Evison§John Parkin§, Richard T. Bryan, Helen Parsons, Nicholas D. James§‡ and Prashant Patel§

 

*St Georges Hospital NHS Trust, London, UK, The Royal Free London NHS Trust, London, UK, University of Birmingham, Birmingham, UK, §University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK, and Clinical Trials Unit, Warwick Medical School, University of Warwick, Coventry, UK
Read the full article

Abstract

Objective

To analyse the impact of centralisation of radical cystectomy (RC) provision for bladder cancer in England, on postoperative mortality, length of stay (LoS), complications and re-intervention rates, from implementation of centralisation from 2003 until 2014. In 2002, UK policymakers introduced the ‘Improving Outcomes Guidance’ (IOG) for urological cancers after a global cancer surgery commission identified substantial shortcomings in provision of care of RCs. One key recommendation was centralisation of RCs to high-output centres. No study has yet robustly analysed the changes since the introduction of the IOG, to assess a national healthcare system that has mature data on such institutional transformation.

Patients and Methods

RCs performed for bladder cancer in England between 2003/2004 and 2013/2014 were analysed from Hospital Episode Statistics (HES) data. Outcomes including 30-day, 90-day, and 1-year all-cause postoperative mortality; median LoS; complication and re-intervention rates, were calculated. Multivariable statistical analysis was undertaken to describe the relationship between each surgeon and the providers’ annual case volume and mortality.

Results

In all, 15 292 RCs were identified. The percentage of RCs performed in discordance with the IOG guidelines reduced from 65% to 12.4%, corresponding with an improvement in 30-day mortality from 2.7% to 1.5% (P = 0.024). Procedures adhering to the IOG guidelines had better 30-day mortality (2.1% vs 2.9%; P = 0.003) than those that did not, and better 1-year mortality (21.5% vs 25.6%; P < 0.001), LoS (14 vs 16 days; P < 0.001), and re- intervention rates (30.0% vs 33.6%; P < 0.001). Each single extra surgery per centre reduced the odds of death at 30 days by 1.5% (odds ratio [OR] 0.985, 95% confidence interval [CI] 0.977–0.992) and 1% at 1 year (OR 0.990, 95% CI 0.988–0.993), and significantly reduced rates of re-intervention.

Conclusion

Centralisation has been implemented across England since the publication of the IOG guidelines in 2002. The improved outcomes shown, including that a single extra procedure per year per centre can significantly reduce mortality and re-intervention, may serve to offer healthcare planners an evidence base to propose new guidance for further optimisation of surgical provision, and hope for other healthcare systems that such widespread institutional change is achievable and positive.

Read more articles of the week

 

Article of the Week: Detection and oncological effect of CTC in patients with variant UCB histology treated with RC

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 accompanying editorial written by a prominent member of the urological community. This blog is 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.

Detection and oncological effect of circulating tumour cells in patients with variant urothelial carcinoma histology treated with radical cystectomy

Armin Soave*, Sabine Riethdorf, Roland Dahlem*, Sarah Minner, Lars Weisbach*, Oliver Engel*, Margit Fisch*, Klaus Pantel† and Michael Rink*

 

*Department of Urology, Institute of Tumor Biology, and Department of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

 

 
Read the full article

How to Cite

Soave, A., Riethdorf, S., Dahlem, R., Minner, S., Weisbach, L., Engel, O., Fisch, M., Pantel, K. and Rink, M. (2017), Detection and oncological effect of circulating tumour cells in patients with variant urothelial carcinoma histology treated with radical cystectomy. BJU International, 119: 854–861. doi: 10.1111/bju.13782

Abstract

Objectives

To investigate for the presence of circulating tumour cells (CTC) in patients with variant urothelial carcinoma of the bladder (UCB) histology treated with radical cystectomy (RC), and to determine their impact on oncological outcomes.

Patients and methods

We prospectively collected data of 188 patients with UCB treated with RC without neoadjuvant chemotherapy. Pathological specimens were meticulously reviewed for pure and variant UCB histology. Preoperatively collected blood samples (7.5 mL) were analysed for CTC using the CellSearch® system (Janssen, Raritan, NJ, USA).

aotw-results-4

Results

Variant UCB histology was found in 47 patients (25.0%), most frequently of squamous cell differentiation (16.5%). CTC were present in 30 patients (21.3%) and 12 patients (25.5%) with pure and variant UCB histology, respectively. At a median follow-up of 25 months, the presence of CTC and non-squamous cell differentiation were associated with reduced recurrence-free survival (RFS) and cancer-specific survival (pairwise P ≤ 0.016). Patients without CTC had better RFS, independent of UCB histology, than patients with CTC with any UCB histology (pairwise P < 0.05). In multivariable analyses, the presence of CTC, but not variant UCB histology, was an independent predictor for disease recurrence [hazard ratio (HR) 3.45; P < 0.001] and cancer-specific mortality (HR 2.62; P = 0.002).

Conclusion

CTC are detectable in about a quarter of patients with pure or variant UCB histology before RC, and represent an independent predictor for outcomes, when adjusting for histological subtype. In addition, our prospective data confirm the unfavourable influence of non-squamous cell-differentiated UCB on outcomes.

Read more articles of the week

Editorial: Detection and oncological effect of CTC in patients with variant UCB histology treated with RC

I read this article from Hamburg-Eppendorf with great interest [1]. The treatment of invasive urothelial carcinoma has not significantly progressed in the last 30 years, with survivals currently that are little changed since the first introduction of multi-drug platinum-based chemotherapy in the 1980s. Moreover, the broad application of chemotherapy, whether it is in the preoperative or postoperative domains, is associated with significant morbidity in this generally elderly population. As 60–80% of patients are cured by surgery alone, the broad use of chemotherapy in any setting results in unnecessary morbidity and occasionally mortality in some patients unnecessarily. Multiple patients have a permanent reduction in renal function when platinum is used in this setting. The decision to treat preoperatively is limited by inaccurate clinical staging and in the postoperative setting may be compromised by slow or incomplete surgical recovery.

The measurement of preoperative circulating tumour cells (CTC) provides us with a rational approach to more accurately select patients for neoadjuvant chemotherapy and would seem according to this article to independently predict disease recurrence, even when considering aggressive variant histologies. Examining Figure 2, one finds that even with variant histology, 60% of patients will not recur after cystectomy if they are CTC negative. The differences are even more profound in pure urothelial carcinoma, where the presence of detectable CTC decreases survival by 50%. The authors are to be congratulated for providing us with a potential rational methodology to determine the benefit from neoadjuvant chemotherapy in patients with bladder cancer prior to cystectomy. Next we should await the analysis of clinical trials stratified by CTC status.

Read the full article
Michael O. Koch, Chairman and Professor of Urology

 

Indiana Cancer Pavilion, Indiana University School of Medicine, Indianapolis, IN, USA

 

Reference

 

 

Article of the Week: Identifying predictors of renal function decline after surgery

Every week the Editor-in-Chief selects the 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 accompanying editorial written by a prominent member of the urological community. This blog is 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.

Preoperative predictors of renal function decline after radical nephroureterectomy for upper tract urothelial carcinoma

Matthew Kaag, Landon Trost*, R. Houston Thompson*, Ricardo Favaretto†, Vanessa Elliott, Shahrokh F. Shariat‡, Alexandra Maschino†, Emily Vertosick†, Jay D. Raman and Guido Dalbagni†

Penn State Hershey Medical Center, Hershey, PA, *Mayo Clinic, Rochester, MN, †Memorial Sloan-Kettering Cancer Center, New York, NY, USA, and ‡Medical University of Vienna, Vienna, Austria

Read the full article
OBJECTIVES

To model renal function after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). To identify predictors of renal function decline after surgery, thereby allowing the identification of patients likely to be ineligible for cisplatin-based chemotherapy in the adjuvant setting.

PATIENTS AND METHODS

We retrospectively identified 374 patients treated with RNU for UTUC at three centres between 1995 and 2010. Estimated glomerular filtration rate (eGFR) was calculated using Chronic Kidney Disease Epidemiology Collaboration equation before RNU and at early (1–5 months after RNU) and late (>5 months) time points after RNU. Only patients deemed eligible for cisplatin-based chemotherapy before RNU (preoperative glomerular filtration rate [GFR] ≥60 mL/min/1.73 m2) were included. Multivariable analysis identified the preoperative predictors of eGFR after RNU at early postoperative and late postoperative time points.

RESULTS
A total of 163 patients had an eligible early post-RNU eGFR measurement and 172 had an eligible late eGFR measurement. The median eGFR declined by 32% and did not show a significant trend toward recovery over time (P = 0.4). On multivariable analysis preoperative eGFR and patient age were significantly associated with early and late postoperative eGFR, while Charlson comorbidity index score was significantly associated with late postoperative eGFR alone.
 

CONCLUSIONS
In patients with normal preoperative eGFR (≥60 mL/min/1.73 m2), renal function decreases by one-third after RNU and does not show evidence of recovery over time. Elderly patients and those with pre-RNU eGFR closer to 60 mL/min/1.73 m2 (lower eGFR in the present cohort) are more likely to be ineligible for adjuvant cisplatin-based chemotherapy regimens because of renal function loss after RNU.

 

Read more articles of the week

 

Editorial: ‘Discontent is the first necessity of progress’, Thomas A. Edison

This study from Kaag et al. [1] investigates predictors of renal functional decline after radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC). They evaluate early (2 months) and late (6 months) predictors of renal functional decline, finding that on a multivariable model only age at surgery and preoperative renal function were independently associated with early postoperative function. This is an intuitive finding whereby we expect older patients and those with lower renal function to have a more dramatic decrease in renal function after RNU.

Age, preoperative renal function, and Charlson score were associated with late functional recovery. The latter is a counterintuitive finding, as higher Charlson score was associated with less decrease in renal function. Charlson comorbidity was not significant on univariate analyses. Why it would become significant on multivariate is unclear. Whether it is an artifact related to study methodology or is a real phenomenon will require further study.

Unquestionably, this study [1] adds to the growing discontent of our current management of UTUC. The authors cogently discuss the issues related to better risk stratification as a natural consequence of instituting a neoadjuvant chemotherapy paradigm in those with high-risk disease. Multiple retrospective studies have failed to show a benefit of adjuvant chemotherapy, whereas now we have a matched-cohort study showing significant rates of downstaging and complete remission [2], and as well significantly improved 5-year survival, with institution of a neoadjuvant paradigm [3]. One cannot view the dismal outcomes of this disease without being discontent and wishing for progress. We need to continue getting out the message to not only urologists who reflexively institute RNU in patients with a risk-unstratified upper tract filling defect, but as well many medical oncologists who can only function based on guidance from level I data, which for this disease, will be a long time coming.

Read the full article

Surena F. Matin

Department of Urology, MD Anderson Cancer Center, Houston, TX, USA

References

1 Kaag M, Trost L, Thompson RH et al. Pre-operative predictors of renal function decline following radical nephroureterectomy for upper tract urothelial carcinoma. BJU Int 2014; 114: 674–9

2 Matin SF, Margulis V, Kamat A et al. Incidence of downstaging and complete remission after neoadjuvant chemotherapy for high-risk upper tract transitional cell carcinoma. Cancer 2010; 116: 3127–34

3 Porten S, Siefker-Radtke AO, Xiao L et al. Neoadjuvant chemotherapy improves survival of patients with upper tract urothelial carcinoma. Cancer 2014; 120: 1794–9

Article of the week: Impact of blood transfusion during radical cystectomy

Every week the Editor-in-Chief selects the 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 accompanying editorial written by a prominent member of the urological community. This blog is 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.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from Dr. Kluth discussing his paper.

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

Impact of peri-operative blood transfusion on the outcomes of patients undergoing radical cystectomy for urothelial carcinoma of the bladder

Luis A. Kluth1,3, Evanguelos Xylinas1,4, Malte Rieken1,5, Maya El Ghouayel1, Maxine Sun1, Pierre I. Karakiewicz6, Yair Lotan7, Felix K.-H. Chun3, Stephen A. Boorjian8, Richard K. Lee1, Alberto Briganti9 , Morgan Rouprêt10, Margit Fisch3, Douglas S. Scherr1 and Shahrokh F. Shariat1,2,11

1Department of Urology and 2Division of Medical Oncology, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY, USA, 3Department of Urology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany, 4Department of Urology, Cochin Hospital, Assistance Publique-Hopitaux de Paris, Paris Descartes University, Paris, France, 5Department of Urology, University Hospital of Basel, Basel, Switzerland, 6Department of Urology, University of Montreal, Montreal, QC, Canada, 7Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA, 8Department of Urology, Mayo Medical School and Mayo Clinic, Rochester, MN, USA, 9Department of Urology, Vita-Salute University, Milan, Italy, 10Department of Urology of la Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris, University Paris VI, Faculté de Médicine Pierre et Marie Curie, Paris, France, and 11Department of Urology, Medical University of Vienna, Vienna, Austria

L.A.K. and E.X. contributed equally to this work

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OBJECTIVE

• To determine the association between peri-operative blood transfusion (PBT) and oncological outcomes in a large multi-institutional cohort of patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB).

PATIENTS AND METHODS

• We conducted a retrospective analysis of 2895 patients treated with RC for UCB.

• Univariable and multivariable Cox regression models were used to analyse the effect of PBT administration on disease recurrence, cancer-specific mortality, and any-cause mortality.

RESULTS

• Patients’ median (interquartile range [IQR]) age was 67 (60, 73) years and the median (IQR) follow-up was 36.1 (15, 84) months.

• Patients who received PBT were more likely to have advanced disease (P < 0.001), high grade tumours (P = 0.047) and nodal metastasis (P = 0.004).

• PBT was associated with a higher risk of disease recurrence (P = 0.003), cancer-specific mortality (P = 0.017), and any-cause mortality (P = 0.010) in univariable, but not multivariable, analyses (P > 0.05).

• In multivariable analyses, pathological tumour stage, pathological nodal stage, soft tissue surgical margin, lymphovascular invasion and administration of adjuvant chemotherapy were independent predictors of disease recurrence, cancer-specific mortality and any-cause mortality (all P values <0.002).

CONCLUSIONS

• Patients with UCB who underwent RC and received PBT had a greater risk of disease recurrence, cancer-specific mortality and any-cause mortality in univariable, but not multivariable, analysis.

• Although the greater need for PBT with more advanced disease is probably caused by a number of factors, including surgical and cancer-related factors, the present analysis showed that the disease characteristics rather than need for PBT led to worse outcomes.

 

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