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Editorial: Palliative care in patients with bladder cancer: an opportunity for value improvement?

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The concept of improving value in healthcare translates, in practical terms, to maximizing patient outcomes per dollar spent [1]. Palliative care has been shown to improve quality of life and possibly survival while reducing overall treatment costs amongst the seriously ill by as much as 33% per patient [2]. In this context, appropriate integration of palliative services within urological oncology care can serve as a mechanism for improving value in the field.

In this issue of BJUI, Hugar et al. [3] provide a valuable characterization of the current state of palliative care service utilization for patients with bladder cancer. Within a contemporary population of Medicare beneficiaries, the authors found receipt of palliative care services by only 4.1% of patients with advanced bladder cancer (defined as those with T4, N+, or M+ disease). Most interestingly, this value did not differ in a statistically significant manner from the rate of utilization amongst a broader cohort including all patients with muscle‐invasive (i.e. T2) bladder cancer collectively, nor did the rate of utilization vary by time.

These findings suggest that, generally, clinicians are not taking advantage of a high‐value service for patients with bladder cancer. Furthermore, the fact that utilization rates are not distinctly higher for those who meet criteria for early palliative care under American Society for Clinical Oncology guidelines (i.e. those with metastatic or locally advanced disease) indicates that barriers to adoption may be rooted in factors beyond simple recognition of advanced malignancy.  Considered in the context of this study showing no momentum towards increasing adoption, one must consider what clinical or policy interventions could alter current utilization trends. For more info follow grid-nigeria .

The authors appropriately identify that absence of physician buy‐in and a traditional lack of emphasis on cost‐conscious care are among the possible explanations for the low, flat utilization figures they observed. Indeed, fee‐for‐service reimbursement is generally oriented towards rewarding volume over quality and is known to encourage inefficiencies, high costs, service duplication, and a lack of care coordination. As such, a powerful corrective counterbalance to these forces could include restructuring reimbursement such that clinicians’ financial incentives become more closely aligned with patient outcomes and goals [4]. Palliative care is merely one of the high‐value services that stands to be more appropriately integrated into clinical practice under such reforms.

Value‐oriented alternative payment models, such as bundled payments, have been shown to improve coordination of care amongst providers [5]. And, in fact, there are already data suggesting that integration of palliative services into an improved care coordination environment yields improved outcomes. Check here at spiritofthesea  for more details. For example, a comprehensive care management plan known as the Aetna Compassionate Care Programme was shown to decrease lengths of inpatient hospitalization while resulting in overall end‐of‐life cost savings of 22% [6].

As the appropriate rate of palliative care utilization in muscle‐invasive bladder cancer remains open to debate, so too does the question of which interventions could assist in moving towards that level. In that sense, employing reimbursement incentives as a driver of more appropriate utilization of palliative care services should be viewed as but one of many potential approaches to improve the practice patterns illustrated in the present study. Future research will be necessary to better elucidate both the barriers to palliative care adoption as well as the most effective tactics to overcome them. The authors should be commended for providing the preliminary contextual data for these conversations, as urologists seek to integrate palliative services properly into high‐value care delivery for patients with advanced malignancy.

 

References

  1. Kaplan, RS, Porter, ME. How to solve the cost crisis in health care. Harv Bus Rev 2011; 89: 46– 52
  2. Brumley, R, Enguidanos, S, Jamison, P et al. Increased satisfaction with care and lower costs: results of a randomized trial of in‐home palliative care. J Am Geriatr Soc 2007; 55: 993– 1000
  3. Hugar, L, Lopa, S, Yabes, J et al. Palliative care use among patients with bladder cancer. BJU Int 2019; 123: 968– 75
  4. Miller, HD. From volume to value: better ways to pay for health care. Health Aff (Millwood) 2009;28: 1418– 28
  5. Bakker, DH, Struijs, JN, Baan, CB et al. Early results from adoption of bundled payment for diabetes care in the Netherlands show improvement in care coordination. Health Aff (Millwood)2012; 31: 426– 33
  6. Spettell, CM, Rawlins, WS, Krakauer, R et al. A comprehensive case management program to improve palliative care. J Palliat Med 2009; 12: 827– 32

 

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

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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 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
Read the full article

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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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

Editorial: The burden of urological cancers in low‐ and middle‐income countries

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The burden of cancer in low‐ and middle‐income countries (LMICs) continues to rise [1]. Evaluation of geographical differences in cancer mortality statistics is specifically of interest in LMICs as (inter)national guidelines are potentially less embedded in standard care, and objective measurements to assess underlying mechanisms/explanations for the burden of cancer are often lacking. Monitoring mortality statistics in these countries can thus help assess the effectiveness of national and regional health systems in treating and caring for patients with cancer [1].

Torres‐Roman et al. [2] deserve to be congratulated for their efforts to monitor mortality rates for prostate cancer at both a regional and national level in Peru. The CONCORD initiative from the WHO previously reported prostate cancer statistics for Peru, but data were limited to the capital area of Lima [1]. Torres‐Raman et al. [2] report prostate cancer mortality rates between 2005 and 2014 based on data from the Peruvian Ministry of Health, which covers ~70% of all healthcare providers in Peru. Apart from an overall increase of 15% in mortality rates, substantial variation was observed by geographical region. Mortality rates increased by 16% in the coastal region and highlands, whereas in the rainforest region the rates decreased by 19% [2]. One potential explanation for these observed differences could be the difference in ethnic and racial characteristics. The coastal region in Peru has a strong African influence and also has a larger proportion of men aged >65 years. In addition to potential differences in access to healthcare, some of the variation in prostate cancer mortality statistics most likely reflects a deficiency in reporting systems. Even though this study has its limitations due to missing data and lack of information on other important variables, such as ethnicity and socioeconomic status, it provides a first base for a critical assessment of prostate cancer care in Peru.

Studies like this one from Torres‐Roman et al. [2] show that there is a need for improvement and standardisation of (prostate) cancer care in LMICs, but also a need for improvement in data capturing, so that objective measurements can be put in place. The years of healthy life lost due to prostate cancer, as well as other urological cancers, in LMICs is increasing substantially. Even though each tumour group has its own specifications in terms of prevention and control, an epidemiological assessment of cancer burden based on the experience for urological cancers (i.e., prostate, bladder, kidney and testicular) can therefore inform future assessments of cancer burden. The urological tumour group covers both common and less common cancers (e.g. prostate vs kidney cancer), sex‐specific and cancers that affect both sexes (e.g. testicular vs bladder cancer), cancers with less known risk factors and those strongly linked with lifestyle risk factors (e.g. prostate vs bladder cancer).

It is encouraging to see an increase in the number of studies evaluating the burden of cancer in LMICs [3]; however, given the consistency in observations of an increase in mortality, there is an urgent need to further invest in prevention and management, as well as the infrastructure to collect all relevant data at a national level in these LMICs. Accurate information about cancer burden and how this varies between regions is essential to plan for an adequate health‐system response.

References

  1. Allemani, C, Matsuda, T, Carlo, V et al. Global surveillance of trends in cancer survival 2000‐14 (CONCORD‐3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population‐based registries in 71 countries. Lancet 2018; 391: 1023– 75
  2. Torres‐Roman, J, Ruiz, E, Martinez‐Herrera, J et al. Prostate cancer mortality rates in Peru and its geographic regions. BJU Int 2019; 123: 595– 601
  3. Carioli, G, Vecchia, C, Bertuccio, P et al. Cancer mortality predictions for 2017 in Latin America. Ann Oncol 2017; 28: 2286– 97

 

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

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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. 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 Hôpitaux de Paris, Pierre et Marie Curie Medical School, University Paris, Paris, France

Read the full article

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.

 

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

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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

 

Article of the month: Effect of timing of an immediate instillation of mitomycin C after TUR in 941 patients with NMIBC

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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 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.

The effect of timing of an immediate instillation of mitomycin C after transurethral resection in 941 patients with non-muscle-invasive bladder cancer

Judith Bosschieter*, R. Jeroen A. van Moorselaar*, André N. Vis*, Tessa van Ginkel*, Birgit I. Lissenberg‐Witte†, Goedele M.A. Beckers* and Jakko A. Nieuwenhuijzen*

 

Departments of *Urology and †Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands

 

Read the full article

Abstract

Objective

To investigate whether the timing of an immediate instillation of mitomycin C (on the day of transurethral resection of bladder tumour [TURBT] or 1 day later) has an impact on time to recurrence of non‐muscle‐invasive bladder cancer (NMIBC).

Patients and Methods

All patients with NMIBC who were enrolled in a prospective trial between 1998 and 2003, and treated with an early mitomycin C instillation (on the day of TURBT or 1 day later), were selected. Statistical analysis was performed with Kaplan–Meier curves and multivariable Cox regression.

Fig. 1 Kaplan–Meier analysis showing time to recurrence for patients treated with an immediate instillation of MMC on the day of TURBT (Day‐0 group) or 1 day after (Day‐1 group).

Results

Administering an instillation of mitomycin C on the day of TURBT or 1 day later did not show a statistically significant difference in time to recurrence in a univariable model (log‐rank P = 0.99). After correcting for the number of scheduled adjuvant instillations, no statistically significant difference could be detected either: hazard ratio 1.05 (95% confidence interval 0.81–1.35, P = 0.74).

Conclusion

These data do not support the hypothesis that a very early instillation (on the day of TURBT) of mitomycin C decreases the risk of recurrence as compared with an early instillation (1 day after TURBT).

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Editorial: Postoperative intravesical chemotherapy has an important role in reducing subsequent bladder tumours – why is it not routine?

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Transurethral resection of bladder tumour (TURBT) is a frequent operation performed by urologists worldwide. Although on occasion the procedure can be quite challenging, the majority are relatively straightforward with little morbidity. In most cases, where the medical system allows, it is an outpatient procedure. Nonetheless, with the exception of small low‐grade tumours the patient is anaesthetised. It is costly, as the procedure requires medical clearance, an operating room team and equipment.

Most patients with bladder cancer have Ta or less frequently T1 tumours. Despite an initial TURBT, 30–80% of patients develop another tumour. Most are new tumours and some may be recurrences. The reasons for the high ‘recurrence’ rate are the continued impact of the carcinogen, e.g. cigarettes, incomplete resection, missed tumours, and tumour implantation on the altered urothelium. The urologist can help reduce these events by stressing the importance of limiting carcinogen exposure e.g. smoking cessation, striving to perform a complete TURBT, reviewing the entire bladder after the TURBT to avoid missing tumours (using narrow‐band imaging or fluorescent cystoscopy if available), and limiting implantation of tumour cells on the altered urothelial surface with the use of postoperative intravesical chemotherapy (POIVC).

There is a large body of evidence that POIVC reduces the chance of a subsequent tumour [1]. I became convinced that implantation occurs after animal studies demonstrated that bladder cancer cells placed into the bladder preferentially implant and grow only if the urothelial surface had been cauterised or otherwise damaged prior to exposure to the bladder cancer cells [2]. Prospective randomised trials eventually confirmed the benefit of POIVC [3]. The paper published in this issue of the BJUI by Bosschieter et al. [4] indicates that POIVC is equally effective if given the same day or the day after TURBT. Thus, if there are obstacles to instilling the medication on the day of the TURBT the drug can be administered the following day.

The evidence in favour of POIVC for bladder tumours is particularly impressive for Grade 1–2 Ta tumours. In my view, all patients with primary or ‘recurrent’ single or multiple papillary Grade 1–2 Ta tumours are the optimal candidates to receive POIVC [5]. POIVC is recommended by the European Association of Urology (EAU) and AUA/Society of Urologic Oncology (SUO) [6,7] yet, the adoption of this guideline is far from uniform. I queried my colleagues from the International Bladder Cancer group (IBCG), as they are conversant in the scientific basis for POIVC and represent several countries with different medical systems [8]. Their comments are pertinent and consistent with my understanding of the issues. Here are some of the common reasons for not following the guidelines: (i) Some urologists are not convinced that the reduction in the ‘recurrence’ rate is sufficient to use POIVC. (ii) The most common chemotherapeutic agent for POIVC in the USA is mitomycin C and it is expensive. The cost for 40 mg is ~$1000. It is approximately $500 in Europe. (iii) Hospitals have rules regarding the delivery of chemotherapy and the pharmacy and nursing departments may not make it easy to instil the drug in the postoperative setting. Some hospitals require notification a day before the surgery and the drug is wasted if the drug is not used. (iv) Urologists are concerned about extravasation and uncertainty of the tumour grade and stage. There may be other reasons but these help explain why POIVC is not routine.

On the other hand many patients with bladder cancer require frequent TURBTs. I am certain that following an uneventful TURBT or office cauterisation for Grade 1–2 Ta bladder cancer, they would choose to receive POIVC if properly informed. Urologists are proficient at judging whether a tumour fits the criteria for POIVC and if they underestimate the grade or stage the patient may still benefit. If urologists cannot instil the chemotherapy on the day of the TURBT, they can instil the drug the following day without compromising effectiveness. I believe it is our job to do what we can to help our patients and in this instance we should do our best to minimise subsequent tumour events, which includes the use of adjuvant chemotherapy.

Mark S. Soloway

Memorial Hospital Hollywood, Miami, FL, USA

References

  1. Perlis N, Zlotta AR, Beyene J, Finelli A, Fleshner NE, Kulkarni GS. Immediate post‐ transurethral resection of bladder tumor intravesical chemotherapy prevents non‐muscle invasive bladder tumor recurrence: an updated meta‐analysis on 2548 patients and quality –of‐evidence review. Eur Urol 2013; 64: 421–30
  2. Weldon TE, Soloway MS. Susceptibility of urothelium to neoplastic cellular implantation. Urology 1975; 5: 824–7
  3. Tolley DA, Hargreave TB, Smith PH et al. Effect of intravesical mitomycin C on recurrence of newly diagnosed superficial bladder cancer: interim report from the Medical Research Council Subgroup on Superficial Bladder cancer. Br Med J 1988; 296: 1259–61
  4. Bosschchieter J, von Moorselaar JA, Vis AN et al. The effect of timing of an immediate instillation of mitomycin C after transurethral resection in 941 patients with non‐muscle‐invasive bladder cancer. BJU Int 2018; 122: 571–5
  5. Klaassen Z, Soloway MS. European Association of Urology and American Urological Association/Society of Urologic Oncology guidelines on risk categories for non‐muscle‐invasive bladder cancer may lead to overtreatment for low‐grade Ta bladder tumors. Urology 2017; 105: 14–7
  6. Babjuk M, Böhle A, Burger M et al. EAU guidelines in non‐muscle invasive urothelial carcinoma of the bladder: update 2016. Eur Urol 2017; 71: 447–61
  7. Chang SS, Boorjian SA, Chou R et al. Diagnosis and treatment of non‐muscle invasive bladder cancer: AUA/SUO guideline. J Urol 2016; 196: 1021–9
  8. Brausi M, Witjes F, Lamm D et al. A review of current guidelines and best proactive recommendations for the management of nonmuscle invasive bladder cancer by the International Bladder Cancer Group. J Urol 2011; 186: 2158–67

 

Article of the Week: Impact of bladder cancer on health‐related quality of life

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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.

Impact of bladder cancer on health‐related quality of life

Angela B. Smith*†, Byron Jaeger‡, Laura C. Pinheiro§, Lloyd J. Edwards‡, Hung-Jui Tan*†, Matthew E. Nielsen*†¶ and Bryce B. Reeve†§

 

*Department of Urology , †Lineberger Comprehensive Cancer Center, Multidisciplinary Genitourinary Oncology, ‡Department of Biostatistics, Gillings School of Global Public Health, §Department of Health Policy and Management, Gillings School of Global Public Health , and Department of Epidemiology, Gillings School of Global Public Health, UNC, Chapel Hill, NC, USA

 

Read the full article

Abstract

Objectives

To identify changes in health‐related quality of life (HRQoL) after diagnosis of bladder cancer in older adults in comparison with a group of adults without bladder cancer (controls).

Patients and Methods

Data from the Surveillance, Epidemiology and End Results registries were linked with Medicare Health Outcomes Survey (MHOS) data. Medicare beneficiaries aged ≥65 years in the period 1998–2013, who were diagnosed with bladder cancer between baseline and follow‐up through the MHOS, were matched with control subjects without cancer using propensity scores. Linear mixed models were used to estimate predictors of HRQoL changes.

Results

After matching, 535 patients with bladder cancer (458 non‐muscle‐invasive bladder cancer [NMIBC] and 77 with muscle‐invasive bladder cancer [MIBC]) and 2 770 control subjects without cancer were identified. Both patients with NMIBC and those with MIBC reported significant declines in HRQoL scores over time vs controls: physical component summary −2 and −5.3 vs −0.4, respectively; bodily pain −1.9 and −3.6 vs −0.7; role physical −2.7 and −4.7 vs −0.7; general health −2.4 and −6.1 vs 0; vitality −1.2 and −3.5 vs −0.1; and social functioning −2.1 and −5.7 vs −0.8. All scores ranged from 0 to 100. When stratified by time since diagnosis, HRQoL improved over 1 year for some domains (role physical), but remained lower across most domains.

Conclusions

After diagnosis, patients with bladder cancer experienced significant declines in physical, mental and social HRQoL relative to controls. Decrements were most pronounced among individuals with MIBC. Methods to better understand and address HRQoL decrements among patients with bladder cancer are needed.

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