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Editorial: The bladder cancer conundrum: how do we treat the right tumour with the right treatment, at the right time?

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The bladder cancer conundrum is how to accurately determine the type of tumour, treatment and timing that is ideal for each patient? This is epitomised by the use of neoadjuvant chemotherapy (NAC) for muscle‐invasive bladder cancer (MIBC). MIBC is a deadly disease; if untreated, the 2‐year mortality rate is 85% [1] and even if treated the overall survival (OS) rate at 5 years is 50%. In this context, NAC is appealing because it may improve outcomes. In 2003, a landmark study by Grossman et al. [2] examined NAC prior to radical cystectomy (RC) for MIBC. The median survival (44 vs 77 months, P = 0.06) and pT0 rates, which equate to the best survival rates (30% vs 15%, P < 0.001), were improved with NAC. A meta‐analysis of 11 randomised control trials in >3000 patients reported an OS benefit of 5% at 5 years with platinum‐based NAC [3]. Whilst NAC improves outcomes, especially for those patients who achieve pT0, it is also important to examine outcomes for patients with persistent MIBC and to determine if NAC is helpful in those patients.

In this issue of the BJUI, Lane et al. [4] attempt to answer this question by examining outcomes for patients with persistent MIBC after RC alone or NAC followed by RC. Using Surveillance, Epidemiology, and End Results (SEER)‐Medicare data, the authors examined 1505 patients that underwent RC alone and 381 patients that received NAC and RC from 2004 to 2011. The authors report that after propensity weighted Kaplan–Meier analysis, the 5‐year OS rate was improved amongst patients that received NAC and RC as compared to patients that had RC alone if there was pT2–T4N0M0 disease on final pathology (43.5% vs 37.2%, P = 0.001). However, there was no difference in cancer‐specific survival (CSS) for NAC with RC compared to only RC (53.7% vs 58.4%, P = 0.76). After adjusting for confounders, the authors found similar results. The use of NAC and RC was found to have an OS benefit (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.67–0.94; P = 0.006) for pT2–4N0M0 patients but not a CSS benefit (HR 0.88, 95% CI 0.72–1.08; P = 0.23).

Since previous studies have established the value of NAC in patients that are down‐staged to pT0 disease, the authors also focused their subset analysis on patients not down‐staged and instead had persistent MIBC. On subset analysis, NAC and RC patients with pT2N0M0 disease had an OS but no CSS benefit. For pT3–T4N0M0 patients, there was no OS or CSS benefit. This may suggest that a subset of non‐responders, such as those with pT2 disease, may experience some benefit from NAC despite persistent disease. Lastly, it is worth noting that whilst NAC improves outcomes, is better tolerated before surgery than adjuvant therapy, and is supported by high‐quality evidence, utilisation remains suboptimal. In this study [4], 381 of 1886 patients (or only 20%) had NAC and only 55% of these received cisplatin‐based therapy. Utilisation patterns vary and updated studies may show different results though. Overall, the authors should be congratulated for a study that is relevant, thoughtful and directed at an important clinical topic.

In this study [4], one issue that is raised is the challenges of accurate preoperative staging. The authors in this paper analysed patients according to pathological stage to limit confounding, as determining the exact stage of patients prior to NAC and RC cannot be done exactly. In this study, pT2 patients had on OS benefit after NAC but pT3–4 patients did not benefit. Clinical staging relies on transurethral resection, imaging and examination under anaesthesia to establish the diagnosis. Without final staging, it is difficult to precisely parse out which patients are clinical T2 vs T3 disease before RC. Predicting which patients are non‐responders is particularly important because these patients may be exposed unnecessarily to the risks of chemotherapy and may have delays in surgery that can negatively impact their outcomes. Therefore, even if the optimal treatment is known, identifying which patients will benefit can be challenging.

Fortunately, there is an exciting future for MIBC on the horizon. First, traditionally bladder cancer staging relies on determining the depth of invasion. In the future, more refined categorisation may help better characterise tumour subtypes. Through innovative multiplatform analyses, an improved understanding of distinct subtypes in bladder cancer has emerged [5]. Consequently, better subtype recognition may herald more targeted, and effective, therapy. Next, it is essential to determine the right type of treatment. Now, NAC is the standard of care for MIBC. However, there are several exciting trials examining other effective options to be used alternatively or synergistically. For example, the use of immunotherapy in the preoperative space is being studied and may shift how we manage MIBC. Lastly, the question of timing is key. Now, the order of surgery and systemic therapy may be a new frontier and perhaps the most significant question we are trying to solve. The possibility of understanding new subtypes of tumours and having new treatment options may require new timing for specific therapies in certain patients. It is conceivable that certain subtypes would be best managed with systemic therapy immediately whilst others with upfront surgery.

Certainly, more work needs to be done. So, what can we do now? We can promote the overall well‐being of our patients. Urologists can be conduits to help patients live healthy lifestyles and engage in behaviours that will promote psychological stability and physical strength. Encouraging daily activity, increasing fruit and vegetable consumption and, if needed, weight loss are options. Smoking cessation represents an imperative opportunity where urologists can make a positive impact [6]. Prehabilitation programmes focused on preparation for surgery can be done during NAC or while waiting for surgery and incorporate these elements. In this way, waiting time is leveraged to make small but cumulative improvements – ‘a little bit at a time’ is possible.

For now, we will continue to study the bladder cancer conundrum: subtypes of tumours, various treatments, and the best timing for therapy. Regardless of these results, it is likely patients with bladder cancer will still need some combination of surgery, systematic therapy and supportive care while they heal. In the interim, promoting well‐being is one way to help patients live healthier lives whilst making them more resilient to undergo whatever treatments may emerge next.

by Matthew Mossanen and Adam S. Kibel

References

  1. Prout, GR, Marshall, VF. The prognosis with untreated bladder tumors. Cancer 1956; 9: 551– 8
  2. Grossman, HB, Natale, RB, Tangen, CM et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med 2003; 349: 859– 66
  3. Advanced Bladder Cancer Overview Collaboration. Neoadjuvant chemotherapy for invasive bladder cancer. Cochrane Database Syst Rev 2005; 2: CD005246.
  4. Lane, G, Risk, M, Fan, Y, Krishna, S, Konety, B. Persistent muscle‐invasive bladder cancer after neoadjuvant chemotherapy: an analysis of Surveillance, Epidemiology and End Results‐Medicare data. BJU Int 2019; 123: 818– 25
  5. Robertson, AG, Kim, J, Al‐Ahmadie, H et al. Comprehensive molecular characterization of muscle‐invasive bladder cancer. Cell 2018; 174: 1033
  6. Mossanen, M, Caldwell, J, Sonpavde, G, Lehmann, LS. Treating patients with bladder cancer: is there an ethical obligation to include smoking cessation counseling? J Clin Oncol 2018; 36: 3189– 91

Video: Centralisation of RC for bladder cancer in England

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

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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

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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

 

1 Goossens-Laan CA, Gooiker GA, van Gijn W et al. A systematic review and meta-analysis of the relationship between hospital/surgeon volume and outcome for radical cystectomy: an update for the ongoing debate. Eur Urol 2011; 59: 775–83

 

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: 217–24 166

 

 3 Finks JF, Osborne NH, Birkmeyer JD. Trends in hospital volume and operative mortality for high-risk surgery. N Engl J Med 2011; 364: 2128–37

 

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. e7–532.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: 319–27

 

6 Birkmeyer JD, Siewers AE, Marth NJ, Goodman DC. Regionalization of high-risk surgery and implications for patient travel times. JAMA 2003; 290: 2703–8

 

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

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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 George’s 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: Detecting SNs in patients with BCa intra-operatively

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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.

Radio-guided sentinel lymph node detection and lymph node mapping in invasive urinary bladder cancer: a prospective clinical study

Firas Aljabery1,2,*, Ivan Shabo2,3,4, Hans Olsson2,5, Oliver Gimm2,6 and Staffan Jahnson1,2

1 Department of Urology, Region Östergötland, Linköping University Hospital, Linköping, Sweden, 2 Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, sweden 3 Endocrine and Sarcoma Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden 4 Department of Breast and Endocrine Surgery, Karolinska University Hospital, Solna Stockholm, Sweden 5 Department of Pathology, Region Östergötland, Linköping University Hospital, Linköping, Sweden 6 Department of Surgery, Region Östergötland, Linköping University Hospital, Linköping, Sweden

Read the full article

Abstract

Objectives

To investigate the possibility of detecting sentinel lymph nodes (SNs) in patients with urinary bladder cancer (BCa) intra-operatively and whether the histopathological status of the identified SNs reflected that of the lymphatic field.

Patients and Methods

We studied 103 patients with BCa pathological stage T1–T4 who were treated with cystectomy and pelvic lymph node (LN) dissection during 2005–2011 at the Department of Urology, Linköping University Hospital. Radioactive tracer Nanocoll 70 MBq and blue dye were injected into the bladder wall around the primary tumour before surgery. SNs were detected ex vivo during the operation with a handheld Geiger probe (Gamma Detection System; Neoprobe Corp., Dublin, OH, USA). All LNs were formalin-fixed, sectioned three times, mounted on slides and stained with haematoxylin and eosin. An experienced uropathologist evaluated the slides.

Results

The mean age of the patients was 69 years, and 80 (77%) were male. Pathological staging was T1–12 (12%), T2–20 (19%), T3–48 (47%) and T4–23 (22%). A mean (range) number of 31 (7–68) nodes per patient were examined, totalling 3 253 nodes. LN metastases were found in 41 patients (40%). SNs were detected in 83 of the 103 patients (80%). Sensitivity and specificity for detecting metastatic disease by SN biopsy (SNB) varied between LN stations, with average values of 67% and 90%, respectively. LN metastatic density (LNMD) had a significant prognostic impact; a value of ≥8% was significantly related to shorter survival. Lymphovascular invasion (LVI) occurred in 65% of patients (n = 67) and was significantly associated with shorter cancer-specific survival (P < 0.001).

Conclusion

We conclude that SNB is not a reliable technique for peri-operative localization of LN metastases during cystectomy for BCa; however, LNMD has a significant prognostic value in BCa and may be useful in the clinical context and in BCa oncological and surgical research. LVI was also found to be a prognostic factor.

Read more articles of the week

Editorial: Positive messages for bladder cancer management in negative sentinel lymph node study

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I encourage you to read the study by Aljabery et al. [1] in this edition of BJUI. Their findings are based on some very solid methodology and I think provide a robust answer to their question, which often in science means a ‘negative’ result. The principle of sentinel lymph node biopsy (SLNB) needs no introduction. It is primarily intended to detect the principal LN draining a tumour, allowing its removal and pathological determination of LN metastasis status in that individual [2].The avoidance of an unnecessary LN dissection (LND) and its associated risks is at the heart of any SLNB strategy. On the other hand, particularly for bladder cancer, there is a recognition that a higher number of LNs removed at the time of surgery confers a survival advantage to patients through more accurate staging [3]. With greater numbers of LNs removed pN0 patients are more likely to be truly N0 and pN1 patients with limited metastases have a greater chance that all disease has been completely excised. Thus, when considering SLNB in bladder cancer there is the usual conflict between maximising oncological benefit and minimising surgical harm.Aljabery et al. [1] present an excellent series of cystectomies with a 100% negative margin rate and mean LN count of 30. The 40% rate of LN involvement, is perhaps partly due to the meticulous triple sectioning of each excised LN. Their SLN technique involved four cystoscopic injections to the bladder wall surrounding the tumour and focused on the biggest lesion in multiple tumour cases. The LNs were removed in their packets and studied after removal from the patient. While this is likely to be a more precise method for determining the site of the SLN, it clearly differs from the approach one would take if trying to avoid LND in negative-SLN cases. Furthermore, examination of LNs was performed after formalin fixation. Typically when using SLN techniques frozen sections are also used to guide surgeons during surgery.The results clearly show that SLNB using radiolabelled nanocolloid does not allow accurate identification of pathologically LN-negative patients who could then avoid a complete LN dissection. Sensitivity of the technique in the detection of positive LNs ranged from 67% to 90% at the various LN stations. Overall, of patients with an identifiable SLN that was negative, 19% of patients had positive LNs elsewhere (81% negative predictive value). Effectively one in five patients who might be reassured by a negative SLN result would in fact have undetected positive LNs left behind if this technique were employed. Furthermore, this estimation does not consider errors likely to be introduced with in situ SLN identification and the use of frozen-section analysis rather than non-time-critical analysis of formalin-fixed sections.In such a dangerous disease such inaccuracy is not tolerable and so I totally agree with the authors’ [1] findings that SLNB of pelvic LNs at the time of radical cystectomy for bladder cancer is not a reliable technique for identifying LN metastasis.The positive messages from this study [1] are worth noting by those learning and undertaking cystectomy. The authors’ meticulous approach to surgery is evident from the methodology described and the accumulation of such a well-characterised series. This must be a contributing factor in achieving a 100% negative surgical margin rate and such consistently high LN yields. This should certainly be the aim of all cystectomists. The appropriate time, skill and patience should be given to this step and it should not be compromised upon, particularly when developing robot-assisted or laparoscopic cystectomy services.The findings that T-stage, N-stage and lymphovascular invasion are linked to survival are not that surprising. However, the use of LN metastatic density as a prognostic marker is interesting, as it is not usually discussed in our multidisciplinary meetings. This measure incorporates nodal tumour burden and the extent of LND. The finding of better outcomes in those with a LN metastatic density of <8% reinforces the message that even in those with LN metastases, removing greater numbers of LNs may improve prognosis. Furthermore, the finding that 30% of unilateral LN-positive tumours also had contralateral LNs settles any arguments for unilateral LN dissections.In a recent systematic review of SLNB in bladder cancer [4], the negative predictive value was found to be 92% compared to 81% in the Aljabery et al. [1] study. The authors of the systematic review suggested that SLNB is a promising technique; perhaps in view of technology advances they reviewed that might improve future outcomes of SLNB. While improvements may be possible, current evidence would not encourage me to consider SLNB using radiolabelled nanocolloid for fear of impairing cancer outcomes.

Congratulations to Aljabery et al. [1] on their work. I hope you find reading their paper as constructive as I did.

Tim Dudderidge
Department of Urology, University Hospital Southampton,
Southampton, Hampshire, UK

Read the full article

References

1 Aljabery F, Shabo I, Olson H, Gimm O, Jahnson S. Radio-guided sentinel lymph node detection and lymph node mapping in invasive urinary bladder cancer: a prospective clinical study. BJU Int 2017; 120: 329–36

2 Gould EA, Winship T, Philbin PH, Kerr HH. Observations on a “sentinel node” in cancer of the parotid. Cancer 1960; 13: 77–8

3 Koppie TM, Vickers AJ, Vora K, Dalbagni G, Bochner BH. Standardization of pelvic lymphadenectomy performed at radical cystectomy. Cancer 2006; 107: 2368–74

4 Liss M, Noguchi J, Lee H, Vera D, Kader AK. Sentinel lymph node biopsy in bladder cancer: systematic review and technology update. Indian J Urol 2015; 31: 170–5

 

Video: Detecting SNs in patients with BCa intra-operatively

/by

Radio-guided sentinel lymph node detection and lymph node mapping in invasive urinary bladder cancer: a prospective clinical study

Read the full article

Abstract

Objectives

To investigate the possibility of detecting sentinel lymph nodes (SNs) in patients with urinary bladder cancer (BCa) intra-operatively and whether the histopathological status of the identified SNs reflected that of the lymphatic field.

Patients and Methods

We studied 103 patients with BCa pathological stage T1–T4 who were treated with cystectomy and pelvic lymph node (LN) dissection during 2005–2011 at the Department of Urology, Linköping University Hospital. Radioactive tracer Nanocoll 70 MBq and blue dye were injected into the bladder wall around the primary tumour before surgery. SNs were detected ex vivo during the operation with a handheld Geiger probe (Gamma Detection System; Neoprobe Corp., Dublin, OH, USA). All LNs were formalin-fixed, sectioned three times, mounted on slides and stained with haematoxylin and eosin. An experienced uropathologist evaluated the slides.

Results

The mean age of the patients was 69 years, and 80 (77%) were male. Pathological staging was T1–12 (12%), T2–20 (19%), T3–48 (47%) and T4–23 (22%). A mean (range) number of 31 (7–68) nodes per patient were examined, totalling 3 253 nodes. LN metastases were found in 41 patients (40%). SNs were detected in 83 of the 103 patients (80%). Sensitivity and specificity for detecting metastatic disease by SN biopsy (SNB) varied between LN stations, with average values of 67% and 90%, respectively. LN metastatic density (LNMD) had a significant prognostic impact; a value of ≥8% was significantly related to shorter survival. Lymphovascular invasion (LVI) occurred in 65% of patients (n = 67) and was significantly associated with shorter cancer-specific survival (P < 0.001).

Conclusion

We conclude that SNB is not a reliable technique for peri-operative localization of LN metastases during cystectomy for BCa; however, LNMD has a significant prognostic value in BCa and may be useful in the clinical context and in BCa oncological and surgical research. LVI was also found to be a prognostic factor.

View more videos

Article of the Week: Introduction of RARC within an established enhanced recovery programme

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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.

Introduction of robot-assisted radical cystectomy within an established enhanced recovery programme

Catherine Miller*,†, Nicholas J. Campain†, Rachel Dbeis†, Mark Daugherty†, Nicholas Batchelor†, Elizabeth Waine† and John S. McGrath†

 

*Urology Department, Torbay Hospital, Torquay, and †Exeter Surgical Health Services Research Unit, Royal Devon and Exeter NHS Foundation Trust, Exeter, Devon, UK

 

Read the full article

How to Cite

Miller, C., Campain, N. J., Dbeis, R., Daugherty, M., Batchelor, N., Waine, E. and McGrath, J. S. (2017), Introduction of robot-assisted radical cystectomy within an established enhanced recovery programme. BJU International, 120: 265–272. doi: 10.1111/bju.13702

Abstract

Objectives

To describe the implementation phase of a robot-assisted radical cystectomy (RARC) programme including side-effect profiles and impact on length of stay (LOS).

Patients and Methods

In all, 114 consecutive patients (82% male) underwent RARC and urinary diversion between April 2013 and December 2015 [ileal conduit (97 patients) and orthotopic neobladder (17)]. Surgery was performed by two surgeons within a designated regional cancer centre. No exclusion criteria were applied. All patients were managed on the Exeter Enhanced Recovery Pathway (ERP) in a unit where embedded enhanced recovery practice was already established. Data were collected prospectively on the national cystectomy registry – the British Association of Urological Surgeons (BAUS) Complex Operations Dataset.

aotw-aug-2017-2

Results

RARC was technically feasible in all but one case. The mean operating time was 3–5 h with an overall transfusion rate of 8.8%. There were higher-grade complications (Clavien–Dindo grade III–IV) in 18.4% of patients, with a 30-day mortality rate of 0.9%. The median (range) LOS after RARC was 7 (3–68) days, with a re-admission rate of 18.4%.

Conclusions

The present series shows that RARC can be safely implemented in a unit experienced in robot-assisted surgery (RAS). Case-selection in this setting is not deemed necessary. There are benefits in terms of lower transfusion rates and reduced LOS. The side-effect profile appears to differ from that of open RC, and despite the fact that complication rate is equivalent; ‘technical’ complications are over-represented in the RAS group. As such, they should improve with experience, recognition, and modification of surgical technique. ERPs can be safely applied to all patients undergoing RARC to maximise the benefits of minimally invasive surgery.

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Editorial: Speeding up recovery from radical cystectomy: how low can we go?

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Radical cystectomy (RC) is the ‘gold standard’ treatment for muscle-invasive bladder cancer (BCa) [1]. It offers the best chance of cure in patients with curable disease and excellent palliation in those with local symptoms from advanced disease. Longitudinal reports suggest many patients accept and adapt to the impact of RC, leading to minimal overall impact on their quality of life [2]. As such, RC also offers a viable alternative to BCG for patients with high-risk non-muscle-invasive BCa. Whilst I recognize the vital role that chemotherapy and radiotherapy play in treating this disease, and that radiotherapy may be a better choice for some patients than RC, it is the morbidity from RC that hinders its wider use and encourages alternatives [3]. For example, studies in the USA show that up to one-third of patients with muscle-invasive cancers do not receive radical treatment [4], and implementation of centralized cancer services in the UK has only now shown survival improvements, as morbidity from RC comes down [5]. The lowering of peri-operative morbidity and mortality from RC is changing the face of the operation and increasing its use.

In this month’s issue of BJUI, Miller et al. [6] combine robot-assisted minimal access surgery with enhanced recovery to report outcomes in a consecutive series of ‘state-of-the-art’ RCs in their study from Exeter, UK. The authors show consistent improvements in outcome, such that length of stay halved over the duration of study recruitment. Importantly, recovery becomes more predictable (as shown by the converging mean and median length of stay figures), although it is unclear as to how many patients had prolonged stays. Whilst the authors should be congratulated for their efforts in delivering this service and for charting its implementation so meticulously, some key descriptive findings are missing. For example, what is the extent of the variation in their outcomes (range and quartiles) and do the data differ among surgeons? What happened to the 25% of patients who stayed longer than 10 days? Did all patients receive all components of their enhanced recovery programme, and if not, which were the most impactful? How did length of stay and complication rates differ by reconstructive choice and reconstructive location (intra- or extracorporeal)? Did patient selection stay the same over time, or did improved outcomes lower the ‘fit for cystectomy’ bar? Many of these answers will be missing, given that the primary source of information was the BAUS major operations registry. This self-completed dataset is extremely valuable for comparisons between units and trends over times, but has limited data complexity and granularity. Finally, whilst the field is moving towards total intracorporeal surgery, the reported complication rates appear similar for extra- and intracorporeal reconstruction, questioning the need for the added complexity of intracorporeal surgery.

Economists, commissioners and patients will want to know the importance of the forces driving these improved outcomes. Do the better outcomes reflect centralization of services, the team’s learning curve, the meticulous use of enhanced recovery or minimally invasive surgery through robotics? The latter has vastly different cost implications from the others. My guess is that, whilst all of these aspects were important, it was volume of service (from centralization) and enhanced recovery that were the main contributors. I speak having had a similar experience in my unit, although we started robotic surgery at a later date than did the present authors, and in the knowledge that this group previously published the dramatic impact of enhanced recovery on their length of stays after open RC [7].

Regardless of these concerns, the outcomes are to be welcomed by urologists and patients, and the team should be congratulated. As length of hospital stay becomes shorter, our next scientific focus should be on out-of-hospital recovery. We rarely see data on time taken to return to normal activity and on how patients adjust after surgery. Whilst return to work is important for younger patients, many patients with bladder cancer are retired so for these patients it is return to quality of life that matters most. This question becomes even more important in an era of centralized care, where many patients recover away from their surgical teams and, conversely, surgical teams are less aware of problems and outcomes. Perhaps it will be out of the hospital that the effort and cost of minimally invasive surgery are justified.

James W.F. Catto
Academic Urology Unit, University of Sheffield, Sheffield, UK

 

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References

 

1 Witjes JA, Comperat E, Cowan NC et al. EAU guidelines on muscle- invasive and metastatic bladder cancer: summary of the 2013 guidelines. Eur Urol 2014; 65: 778–92

 

2 Hardt J, Filipas D, Hohenfellner R, Egle UT. Quality of life in patients with bladder carcinoma after cystectomy: first results of a prospective study. Qual Life Res 2000; 9: 1–12

 

3 Shabsigh A, Korets R, Vora KC et al. Defining early morbidity of radical cystectomy for patients with bladder cancer using a standardized reporting methodology. Eur Urol 2009; 55: 164–74

 

4 Gore JL, Litwin MS, Lai J et al. Use of radical cystectomy for patients with invasive bladder cancer. J Natl Cancer Inst 2010; 102: 802–11

 

5 Hounsome LS, Verne J, McGrath JS, Gillatt DA. Trends in operative caseload and mortality rates after radical cystectomy for bladder cancer in England for 1998–2010. Eur Urol 2015; 67: 1056–62

 

6 Miller C, Campain NJ, Dbeis R et al. Introduction of robot-assisted radical cystectomy within an established enhanced recovery programme. BJU Int 2017; 120: 265–72

 

7 Smith J, Pruthi RS, McGrath J. Enhanced recovery programmes for patients undergoing radical cystectomy. Nat Rev Urol 2014; 11: 437–4

 

Should we abandon live surgery: reflections after Semi-Live 2017

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Prokar_v2Ever since 2002, I have performed live surgery almost every year where it is transmitted to an audience eager to learn. This year I was invited by Markus Hohenfellner to the unique conference, Semi Live 2017 in Heidelberg. To say that it was an eye opener is perhaps stating the obvious. One look at the program will show you that the worlds most respected Urological surgeons had been invited to participate, but with a difference. There was no live surgery. Instead videos of operations – open, laparoscopic and robotic were shared with the attendees “warts and all” as a learning experience. These were not videos designed to show the best parts of an operation. There were plenty of difficult moments, do’s and don’ts and troubleshooting, but all this was achieved without causing harm or potential harm to a single patient.

My highlights were laparoscopic sacrocolpopexy (Gaston), robotic IVC thrombectomy up to the right atrium (Zhang) and reconstructive surgery for the buried penis (Santucci). The event takes place every 2 years and the videos are all available on the meeting app which can be downloaded here and is an outstanding educational resource.

We were treated to a heritage session which included the superstars Walsh, Hautmann, Clayman, Mundy, Schroder and Ghoneim. This was followed by our host Markus Hohenfellner comparing and contrasting the art of Cystectomy and reconstruction by Ghoneim, Stenzl and Studer.

 

Open surgery is certainly not dead yet. The session ended with Seven Pillars of Wisdom from Egypt which turned out to be a big hit on Twitter.

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The editor’s choice session, a new innovation for 2017, allowed me to showcase the Best of BJUI Step by Step, a section that has now replaced Surgery Illustrated with fully indexed and citable HD videos and short papers.

Has live surgery had its day?

Many on Twitter seemed to agree that in 20 years time we might look back and say that it was not the right thing to do.

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Surgeons do not operate “live” every day. Most doctors in a survey, would not subject themselves or their families to be patients during live surgery. Talk about hypocrisy!! Why should it be any different for our patients? Live surgery is NOT a blood sport practised in Roman times….

The counterpoint is that patients often have the services of the best surgeons during live surgery, recorded, edited videos are not quite the same and that the whole affair has become safer thanks to patient advocates and strict guidelines from some organisations like the EAU. Others have banned the practice for good reason. While the debate continues, I for one came away feeling that Semi-Live was as educational, less stressful and much safer for our patients.

 

Prokar Dasgupta @prokarurol
Editor-in-Chief, BJUI 

 

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