Tag Archive for: #blcsm

Posts

Editorial: Time to re-evaluate and refine re-TUR in bladder cancer?

In this issue of BJUI, Gontero et al. [1] present data from a large multi-centre study that should allow us to re-evaluate and refine the indications for re-transurethral resection (TUR) in bladder cancer.

Herr [2] first described this procedure in 1999 and for the past 16 years the indications have remained largely unchanged and are summarised in the latest European Association of Urology guidelines on non-muscle-invasive bladder cancer (NMIBC) [3]:

  • After incomplete initial TUR of bladder tumour (TURBT).
  • If there is no muscle in the specimen after initial resection.
  • In all T1 tumours.
  • In all Grade 3 tumours except primary carcinoma in situ.

In a multi-centre retrospective study of 2 451 patients with high-grade (HG)/Grade 3 (G3) T1 NMIBC treated with BCG, Gontero et al. [1]examined 935 patients who had re-TUR (38% of the total, itself a low figure). Patients were divided into four groups according to the presence or absence of detrusor muscle in the first TURBT specimen:

  • No muscle, no re-TUR
  • No muscle, re-TUR
  • Muscle, no re-TUR
  • Muscle, re-TUR

The authors found that re-TUR only had a positive impact on recurrence, progression, cancer-specific and overall survival, if detrusor muscle was not present in the original specimen. Importantly, in the presence of detrusor muscle in the original specimen, re-TUR did not improve outcomes. The authors conclude that re-TUR may be unnecessary in HG/G3 T1 patients if detrusor muscle is present at the first TURBT.

These findings are important for two reasons: firstly, Herr’s [2] paper was the first to draw attention to the finding that TURBT, a routine urological procedure, was often carried out inadequately. In recent years, the importance of carrying out a high-quality TURBT has been increasingly recognised [4], whilst the presence of detrusor muscle in the TURBT specimen has been shown to be a good measure of the technical quality of a TURBT [5]. This paper [1] further reinforces the importance of obtaining detrusor muscle in the first TURBT. Indeed, as failure to do so results in the patient having to have a second operation and delays their treatment, perhaps we should start to think of a failure to obtain detrusor muscle at the first TURBT in much the same way as positive margin rates are used as a measure of the quality of radical prostatectomy and by inference, the skill of the surgeon.

Secondly, re-TUR arguably serves one overarching purpose: to identify patients with muscle-invasive bladder cancer (MIBC) who have been under-staged by an inadequate first TURBT and who without a re-TUR would be inadequately treated.

Although a secondary role of re-TUR is to identify patients with residual NMIBC, which has some prognostic value, in practice it rarely changes the patient’s management in this setting, which is intravesical therapy usually with BCG. However, in many healthcare systems the timely organisation of a re-TUR within the recommended 6 weeks is challenging and there is usually a further delay of at least 2 weeks until the pathology is reviewed and a patient with NMIBC can finally commence treatment. In this context, it is not surprising that a recent paper in BJUI showed that the interval to re-TUR was a predictor of recurrence and progression and that a re-TUR after 7 weeks was associated with a much worse outcome [6]. It therefore seems logical to reserve re-TUR only for those patients who truly need it, so that limited resources are focused on ensuring that they receive their operation in a timely manner, ideally within 2–4 weeks. If adopted into day-to-day urological practice, the findings by Gontero et al. [1] will allow many patients with HG/G3 T1 and detrusor muscle in the first TURBT specimen to avoid a re-TUR and start intravesical therapy without further delay. Pragmatically, the same should apply to patients with HG/G3 Ta with detrusor muscle in the specimen. On the other hand, HG/G3 T1 patients without detrusor muscle should be fast-tracked for re-TUR as soon as is practicable and certainly no later than 6 weeks.

The article [1] does have some shortcomings. The study design excludes patients with MIBC, so we do not know by comparison how many patients with MIBC were under-staged at the initial TUR based on subsequent re-TUR but as the authors point out, their conclusions would hold true even in this group, as it is very unlikely that one would miss MIBC if there was adequate detrusor muscle in the pathology specimen.

In conclusion, we should consider refining the indications for re-TUR to improve the utilisation of healthcare resources and ensure that for those that need it, a re-TUR is carried promptly whilst for those that do not, essential intravesical treatment is not delayed.

A. Hugh Mostad, Consultant Urologist and Honorary
Senior Lecturer The Royal Surrey County Hospital, Guildford, Surrey, UK

 

References

 

Video: Impact of Re-TUR on BCG-Treated T1 HG/G3 Bladder Cancer

The impact of re-transurethral resection on clinical outcomes in a large multicentre cohort of patients with T1 high-grade/Grade 3 bladder cancer treated with bacille Calmette–Guerin

Paolo Gontero1, Richard Sylvester2, Francesca Pisano1, Steven Joniau3, Marco Oderda1, Vincenzo Serretta4,Stephane Larre5, Savino Di Stasi6, Bas Van Rhijn7, Alfred J.Witjes8, Anne J. Grotenhuis8, Renzo Colombo9, Alberto Briganti9, Marek Babjuk10, Viktor Soukup10, Per-Uno Malmstrom11, Jacques Irani12, Nuria Malats13, Jack Baniel14, RoyMano14, Tommaso Cai15, Eugene K. Cha16, Peter Ardelt17, John Vakarakis18, Riccardo Bartoletti19, Guido Dalbagni20, Shahrokh F. Shariat16, Evanguelos Xylinas16, Robert J.Karnes21 and Joan Palou22

 

1Urology Clinic, Citta della Salute e della Scienza di Torino, University of Studies of Turin, Turin ,4Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, 6Policlinico Tor Vergata-University of Rome, Rome, 9Dipartimento di Urologia, Universita Vita-Salute. Ospedale S. Raffaele, Milan, 15Department of Urology, SantaChiara Hospital, Trento, 19Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy, 2Formerly Department of Biostatistics, EORTC Headquarters, Brussels, 3Oncologic and Reconstructive Urology, Department of Urology, University Hospitals Leuven, Leuven, Belgium, 5Department of Surgical Science, John Radcliffe Hospital, University of Oxford, Oxford, UK, 7Department of Urology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam, 8Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, 10Department of Urology, Motol Hospital, University of Praha, Praha, Czech Republic, 11Department of Urology, Academic Hospital, Uppsala University, Uppsala, Sweden, 12Department of Urology, Centre Hospitalier Universitaire La Miletrie, University of Poitiers, Poitiers, France, 13Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), Madrid, 22Department of Urology, Fundacio Puigvert, University of Barcelona, Barcelona, Spain, 14Department of Urology, Rabin Medical Centre, Tel Aviv, Israel, 16Department of Urology, Weill Medical College of Cornell University in New York City, 20Department of Urology, Memorial Sloan Kettering Cancer Center, New York, NY, 21Department of Urology, Mayo Clinic, Rochester, MN, USA, 17Facharzt fur Urologie, Abteilung fur Urologie. Chirurgische Universitats klinik, Freiburg, Germany, and 18Department of Urology, Sismanoglio Hospital, University of Athens, Athens, Greece

 

Objectives

To determine if a re-transurethral resection (TUR), in the presence or absence of muscle at the first TUR in patients with T1-high grade (HG)/Grade 3 (G3) bladder cancer, makes a difference in recurrence, progression, cancer specific (CSS) and overall survival (OS).

Patients and methods

In a large retrospective multicentre cohort of 2451 patients with T1-HG/G3 initially treated with bacille Calmette–Guérin, 935 (38%) had a re-TUR. According to the presence or absence of muscle in the specimen of the primary TUR, patients were divided in four groups: group 1 (no muscle, no re-TUR), group 2 (no muscle, re-TUR), group 3 (muscle, no re-TUR) and group 4 (muscle, re-TUR). Clinical outcomes were compared across the four groups.

JUlAOTW4Results

Results

Re-TUR had a positive impact on recurrence, progression, CSS and OS only if muscle was not present in the primary TUR specimen. Adjusting for the most important prognostic factors, re-TUR in the absence of muscle had a borderline significant effect on time to recurrence [hazard ratio (HR) 0.67, P = 0.08], progression (HR 0.46, P = 0.06), CSS (HR 0.31, P = 0.07) and OS (HR 0.48, P = 0.05). Re-TUR in the presence of muscle in the primary TUR specimen did not improve the outcome for any of the endpoints.

Conclusions

Our retrospective analysis suggests that re-TUR may not be necessary in patients with T1-HG/G3, if muscle is present in the specimen of the primary TUR.

Read more articles of the week

Article of the Month: Further Evidence that Bladder Cancer Patients should Stop Smoking

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. Smoking in a daily basis can affect your lungs, make sure to improve your indoor air quality just by checking out the latest blaux portable ac reviews.

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.

Trends in the risk of second primary cancer among bladder cancer survivors: a population-based cohort of 10 047 patients

Joris Muller*,, Pascale Grosclaude, Benedicte Lapotre-Ledoux§,Anne-Sophie Woronoff§,**, Anne-Valerie Guizard§,††, Simona Bara§,‡‡, Marc Colonna§,§§Xavier Troussard§,¶¶, Veronique Bouvier§,***, Brigitte Tretarre§,†††, Michel Velten*,,§,‡‡‡ and Jeremie Jegu*,
*Bas-Rhin Cancer Registry, EA 3430, FMTS, University of Strasbourg, Department of Public Health, University Hospital of Strasbourg, Strasbourg, Tarn Cancer Registry, Albi, §
Francim: Reseau francais des registres des cancers, Toulouse, Somme Cancer Registry, Department of Hygiene and Public Health, University Hospital of Amiens, Amiens, **Doubs and Belfort Territory Cancer Registry, University Hospital of Besancon, Besancon, ††Calvados General Cancer Registry, Cancers & Preventions, U 1086 Inserm, Francois Baclesse Centre, Caen, ‡‡Manche Cancer Registry, Cotentin Hospital, Cherbourg-Octeville, §§Isere Cancer Registry, University Hospital of Grenoble, Grenoble, ¶¶Basse-Normandie Haematological Malignancies Cancer Registry, University Hospital of Caen, ***Calvados Digestive Cancer Registry, Cancers & Preventions, U 1086 Inserm, Francois Baclesse Centre, Caen, †††Herault Cancer Registry, Research Center, Montpellier , and ‡‡‡Department of Epidemiology and Biostatistics, Paul Strauss Center, Strasbourg, France
Read the full article

Objectives

To determine whether the risk of second primary cancer (SPC) among patients with bladder cancer (BCa) has changed over past years.

Materials and Methods

Data from 10 French population-based cancer registries were used to establish a cohort of 10 047 patients diagnosed with a first invasive (≥T1) BCa between 1989 and 2004 and followed up until 2007. An SPC was defined as the first subsequent primary cancer occurring at least 2 months after a BCa diagnosis. Standardized incidence ratios (SIRs) of metachronous SPC were calculated. Multivariate Poisson regression models were used to assess the direct effect of the year of BCa diagnosis on the risk of SPC.

JulAOTW1Results

Results

The risk of new malignancy among BCa survivors was 60% higher than in the general population (SIR 1.60, 95% confidence interval [CI] 1.51–1.68). Male patients presented a high risk of SPC of the lung (SIR 3.12), head and neck (SIR 2.19) and prostate (SIR 1.54). In multivariate analyses adjusted for gender, age at diagnosis and follow-up, a significant increase in the risk of SPC of the lung was observed over the calendar year of BCa diagnosis (P for linear trend 0.010), with an SIR increasing by 3.7% for each year (95% CI 0.9–6.6%); however, no particular trend was observed regarding the risk of SPC of the head and neck (P = 0.596) or the prostate (P = 0.518).

Conclusions

As the risk of SPC of the lung increased between 1989 and 2004, this study contributes more evidence to support the promotion of tobacco smoking cessation interventions among patients with BCa.

Read more articles of the week

Controversies in management of high-risk prostate and bladder cancer

CaptureRecently, there has been substantial progress in our understanding of many key issues in urological oncology, which is the focus of this months BJUI. One of the most substantial paradigm shifts over the past few years has been the increasing use of radical prostatectomy (RP) for high-risk prostate cancer and increasing use of active surveillance for low-risk disease [1,2]
Consistent with these trends, this months BJUI features several useful articles on the management of high-risk prostate cancer. The rst article by Abdollah et al. [3] reports on a large series of 810 men with DAmico high-risk prostate cancer (PSA level >20 ng/mL, Gleason score 810, and/or clinical stage T2c) undergoing robot-assisted RP (RARP). Despite high-risk characteristics preoperatively, 55% had specimen-conned disease at RARP, which was associated with higher 8-year biochemical recurrence-free (72.7% vs 31.7%, P < 0.001) and prostate cancer-specic survival rates (100% vs 86.9%, P < 0.001). The authors therefore designed a nomogram to predict specimen-conned disease at RARP for DAmico high-risk prostate cancer. Using PSA level, clinical stage, maximum tumour percentage quartile, primary and secondary biopsy Gleason score, the nomogram had 76% predictive accuracy. Once externally validated, this could provide a useful tool for pre-treatment assessment of men with high-risk prostate cancer. 
Another major controversy in prostate cancer management is the optimal timing of postoperative radiation therapy (RT) for patients with high-risk features at RP. In this months BJUI, Hsu et al. [4] compare the results of adjuvant (6 months after RP with an undetectable PSA level), early salvage (administered while PSA levels at 1 ng/mL) and late salvage RT (administered at PSA levels of >1 ng/mL) in 305 men with adverse RP pathology from the USA Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry. At 6.2 years median follow-up, late salvage RT was associated with signicantly higher rates of metastasis and/or prostate cancer-death. By contrast, there was no difference in prostate cancer mortality and/or metastasis between early salvage vs adjuvant RT. A recent study from the USA National Cancer Data Base reported infrequent and declining use of postoperative RT within 6 months for men with adverse RP pathology, from 9.1% in 2005 to 7.3% in 2011 [5]. As we await data from prospective studies comparing adjuvant vs early salvage RT, the results of Hsu et al. [4] are encouraging, suggesting similar disease-specic outcomes if salvage therapy is administered at PSA levels of <1 ng/mL. 
Finally, this issues Article of the Month by Baltaci et al. [6] examines the timing of second transurethral resection of the bladder (re-TURB) for  high-risk non-muscle-invasive bladder cancer (NMIBC). The management ofbladder cancer at this stage is a key point to improve the overall survival of bladder cancer. Re-TURB is already recommended in the European Association of Urology guidelines [7], but it remains controversial as to whether all patients require re-TURB and what timing is optimal. The range of 26 weeks after primary TURB was established based on a randomised trial assessing the effect of re-TURB on recurrence in patients treated with intravesical chemotherapy [8], but it has not been subsequently tested in randomised trial. Baltaci et al. [6], in a multi-institutional retrospective review of 242 patients, report that patients with high-risk NMIBC undergoing early re-TURB (1442 days) have better recurrence-free survival vs later re-TURB (73.6% vs 46.2%, P < 0.01). Although prospective studies are warranted to conrm their results, these novel data suggest that early re-TURB is signicantly associated with lower rates of recurrence and progression.
 
 
References

 

 

 

4 Hsu CC , Paciorek AT, Cooperberg MR, Roach M 3rd, Hsu IC, Carroll PRPostoperative radiation therapy for patients at high-risk of recurrence after radical prostat ectomy: does timing matter? BJU Int 2015; 116: 71320

 

5 Sineshaw HM, Gray PJ, Efstathiou JA, Jemal A. Declining use of radiotherapy for adverse features after radical prostatectomy: results from the National Cancer Data Base. Eur Urol 2015; [Epub ahead of print]. DOI: 10.1016/ j.eururo.2015.04.003

 

 

7 Babjuk M, Bohle A, Burger M et al. European Association of Urology Guidelines on Non-Muscle-Invasive Bladder Cancer (Ta, T1, and CIS). Available at: https://uroweb.org/wp-content/uploads/EAU-Guidelines- Non-muscle-invasive-Bladder-Cancer-2015-v1.pdf. Accessed September 2015

 

 

Stacy Loeb – Department of Urology, Population Health, and the Laura and Isaac Perlmutter Cancer Center, New York University, New York City, NY, USA

 

Maria J. Ribal – Department of Urology, Hospital Clinic, University of Barcelona, Barcelona, Spain

 
 

Editorial: Can we rely on LVI to determine the need for adjuvant chemotherapy in organ-confined bladder cancer?

The authors of this paper [1] are to be congratulated on exploring lymphovascular invasion (LVI) as a possible singular prognostic marker for time to recurrence and overall survival (OS) in a post hoc analysis of a prospective randomized study that originally explored adjuvant methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy after radical cystectomy based on p53 status. This study is the largest prospective study to date looking at the outcome of LVI in organ-confined urothelial cancer of the bladder.

Lymphovascular invasion represents the first step of dissemination of tumour cells into the lymphatic and blood system which may lead to the formation of metastatic clones. In bladder cancer, our current understanding of the predictive and prognostic role of LVI is mainly based on retrospective data, which are inherently flawed by various selection biases. As pathological tumour and nodal stage, as well as soft-tissue surgical margins, are stronger predictors than is LVI for outcomes in advanced bladder cancer, the authors specifically limited their analysis to the group of patients exhibiting organ-confined disease at radical cystectomy. They found that LVI was associated with time to recurrence and death, while a significant benefit of adjuvant chemotherapy could not be confirmed in a small group of 27 patients with altered p53 expression and LVI. The authors concluded that, although their study did not show a survival benefit for adjuvant chemotherapy in patients with LVI, a possible benefit could not be finally excluded [1].

Indeed, there is still uncertainty about the beneficial impact of adjuvant chemotherapy in bladder cancer. While previous meta-analyses could not show a significant prognostic advantage, a recent update of 945 patients who received adjuvant chemotherapy within nine randomized trials has emphasized its prognostic benefit, especially in lymph node-positive disease [2]. By contrast, a recent report from the European Organisation for the Research and Treatment of Cancer intergroup trial suggests that only patients with node-negative pT3–T4 tumours exhibiting LVI benefit from adjuvant chemotherapy [3]. These heterogeneous data make it difficult to specifically recommend adjuvant chemotherapy in invasive bladder cancer.

The aim of the present study was (and definitely has to be in the future) to outline those patients who do not belong to the roughly 80% of patients who are cured by radical cystectomy without any additional systemic therapy in localized disease. What has been shown in this study is that the presence of LVI definitely influences postoperative outcome. What has not been shown is whether a more or less careful diagnosis of LVI influences time to recurrence and OS after adjuvant chemotherapy, similarly to a negative outcome with regard to p53 status. Do we now believe the two main messages of this paper, which are that LVI does not help us in our decision about which patients might need adjuvant chemotherapy and that there is no room for the argument that adjuvant chemotherapy is better than neoadjuvant chemotherapy because of the histological evidence of LVI?

We are in desperate need of markers [4] in light of the recent literature showing that both neoadjuvant and adjuvant chemotherapy will improve survival in patients with cystectomy as a result of urothelial cancer [5]. Despite the fact that this is one of the largest series of patients with LVI in the specimen, the series is much too incoherent because no central pathology, no mandatory immunohistochemistry, and not even mandatory evaluation of the status in the individual institutions was carried out. We do not even know whether quality control of the pathological evaluations was carried out within each pathology department or hospital, as is mandatory in some parts of the world.

Furthermore, in organ-confined bladder cancer, the invasion depth of the tumour is a key prognosticator of recurrence. In the present study, the only variable associated with a higher risk of LVI was found to be pathological stage (pT1 vs pT2); however, substratification in pT2N0 bladder cancer has also been shown to be of prognostic importance for predicting recurrence after cystectomy [4]. The unknown anatomical extent of lymph node dissection at radical cystectomy makes it difficult to assess the impact of LVI on outcomes because patients with localized tumours and presumed micrometastatic disease (as suggested by LVI) may still be cured with an extended pelvic lymph node dissection [6]. While the authors tried to adjust for this bias by reporting on the number of retrieved lymph nodes, 30% of their patients had < 15 lymph nodes removed at surgery.

In conclusion, the authors of the present study address very important questions, but they fail to provide a clear answer that will change current clinical practice.

Read the full article
Georgios Gakis and Arnulf Stenzl 
Department of Urology, University Hospital Tubingen, Tubingen, Germany

 

References

 

 

Radical cystectomy for bladder cancer – is there a changing trend?

The first #urojc instalment of 2015 discussed the recent European Urology paper ‘Trends in operative caseload and mortality rates after radical cystectomy (RC) for bladder cancer in England for 1998-2010. Hounsome et al., examined a total of 16,033 patients who underwent RC – over the study period 30-day and 90-day mortality rates decreased and 30-day, 90-day, 1-year and 5-year survival rates significantly improved.

Henry Woo (@DrHWoo) suggests this paper is breaking the mould in comparison to other series.

Analysis of the SEER database would suggest otherwise – there has been little or no change in the incidence, survival or mortality rates with respect to bladder cancer over an even longer study period (1973-2009). Likewise, Zehnder noticed no survival improvement in patients undergoing RC over the last three decades (1980-2005).

However, Jim Catto (@JimCatto) and Alexander Kutikov (@uretericbud) were quick to point out the differences between survival rates and mortality rates, although Hounsome et al., reported beneficial outcomes in both parameters.

 

 

 

 

 

 

 

 

In the UK, the Improving Outcomes in Urological Cancers guidance (IOG) recommends patients be considered for RC for muscle invasive bladder cancer (MIBC) and high risk recurrent non-muscle invasive bladder cancer (NMIBC). Key aspects of this guidance include – a minimum caseload requirement for performing RC, an MDT approach and specific 30day mortality rates of 50% despite no change in the incidence of bladder cancer. The reasoning for this is multifactorial but in part due to designated cancer centres are offering surgery to more candidates as a result of service improvements that include service reconfiguration, improved surgical training, neoadjuvant chemotherapy, enhanced recovery principles, and continued improvements in peri-operative care.

The on-line debate moved towards discussing the effect of centralisation of cancer services as a causative factor behind these positive results.

Rather intuitively, in a systematic review in 2011, Goossens-Laan et al., postoperative mortality after cystectomy is significantly inversely associated with high-volume providers.

Although the benefits of being treated in a cancer centre of excellence are undoubted- high volume fellowship trained surgeons, a multidisciplinary approach and improved peri-operative conditions; the impact of distance from central services was broached. O’Kelly et al., postulated a higher stage of prostate cancer based on distance from a tertiary care centre, other studies have shown for a variety of cancers (lung, colon)that distance from a central provider can impact outcomes. Outside of the impact on oncological outcomes, the impact on the patient’s lifestyle as well as the economic consequences were not discussed.

While contrary to this, Jim Catto (@JimCatto) highlighted the deskilling associated with centralisation.

 

 

 

 

 

A further significant implicating factor in the positive results seen in this study is due to the use of neo-adjuvant chemotherapy, a question often posed by the patient.

Rather contentiously, David Chan (@dytcmd) remarked that optimal surgical results have already been achieved, a statement challenged by Jim Catto (@JimCatto).

This study although examining a vast number of patients over a lengthy time period is not without its limitations. Specifically the lack of tumour stage, smoking status and the use of chemotherapy as well as issues surrounding a retrospective study looking at data collected by individual hospital coding systems.

This month’s #urojc attracted substantial coverage on Twitter – keep it up.

Many thanks to those you participated in the debate. We look forward to next month’s #urojc discussion.

Greg Nason (@nason_greg) is a Specialist Registrar in Urology, Beaumont Hospital, Dublin, Ireland

 

Article of the week: Neoadjuvant chemotherapy for bladder cancer does not increase risk of perioperative morbidity

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 prominent members 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 Angela Smith and David Johnson discussing their paper.

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

Neoadjuvant chemotherapy for bladder cancer does not increase risk of perioperative morbidity

David C. Johnson*, Matthew E. Nielsen*†‡, Jonathan Matthews*, Michael E. Woods*, Eric M. Wallen*, Raj S. Pruthi*, Matthew I. Milowsky*†§ and Angela B. Smith*

*Department of Urology, University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, Cancer Outcomes Research Group, Multidisciplinary Genitourinary Oncology, Department of Epidemiology, Gillings School of Global Public Health, and §Department of Medicine, Division of Hematology/Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Read the full article
OBJECTIVE

To determine whether neoadjuvant chemotherapy (NAC) is a predictor of postoperative complications, length of stay (LOS), or operating time after radical cystectomy (RC) for bladder cancer.

PATIENTS AND METHODS

A retrospective review of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was performed to identify patients receiving NAC before RC from 2005 to 2011. Bivariable and multivariable analyses were used to determine whether NAC was associated with 30-day perioperative outcomes, e.g. complications, LOS, and operating time.

RESULTS

Of the 878 patients who underwent RC for bladder cancer in our study, 78 (8.9%) received NAC. Excluding those patients who were ineligible for NAC due to renal insufficiency, 78/642 (12.1%) received NAC. In all, 457 of the 878 patients (52.1%) undergoing RC had at least one complication ≤30 days of RC, including 43 of 78 patients (55.1%) who received NAC and 414 of 800 patients (51.8%) who did not (P = 0.58). On multivariable logistic regression, NAC was not a predictor of complications (P = 0.87), re-operation (P = 0.16), wound infection (P = 0.32), or wound dehiscence (P = 0.32). Using multiple linear regression, NAC was not a predictor of increased operating time (P = 0.24), and patients undergoing NAC had a decreased LOS (P = 0.02).

CONCLUSIONS

Our study is the first large multi-institutional analysis specifically comparing complications after RC with and without NAC. Using a nationally validated, prospectively maintained database specifically designed to measure perioperative outcomes, we found no increase in perioperative complications or surgical morbidity with NAC. Considering these findings and the well-established overall survival benefit over surgery alone, efforts are needed to improve the uptake of NAC.

Read more articles of the week

Editorial: Unveiling the surgical risk associated with neoadjuvant chemotherapy in bladder cancer

In this issue of BJU International, Johnson et al. [1] examine the association between neoadjuvant chemotherapy (NAC) for bladder cancer and 30-day morbidity related to radical cystectomy (RC). Level 1 evidence supports use of cisplatin-based NAC for bladder cancer; a meta-analysis of 11 randomised trials including 3005 patients who received NAC found a 5% absolute increase in 5-year overall survival and a 9% absolute increase in 5-year disease-free survival compared with RC alone [2]. Despite this, recent studies have reported underutilisation of NAC at ≈20% [3], with several reasons proposed for this ‘non-compliance’ to guidelines. A 2013 National Cancer Data Base (NCDB) analysis found that increasing age, lower patient income, and treatment at a non-academic institution (P < 0.01) negatively influenced the receipt of NAC, while higher clinical stage and fewer comorbid conditions were associated with higher likelihood of receiving NAC (P < 0.01) [3].

Another relevant concern is that NAC may increase perioperative complications for RC given the toxicities associated with chemotherapy, advanced age and often high rates of renal and cardiac comorbidities among potential candidates [4]. Credit should be given to Millikan et al. [5] for first negating this fear in 2001 with a randomised trial comparing NAC vs adjuvant chemotherapy in patients with bladder cancer; this study did not find any increase in perioperative morbidity.

The present analysis by Johnson et al. [1] further debunks this misconception in contemporary practice (2005–2011), drawing on the American College of Surgeons National Surgical Quality Improvement Program (NSQIP), which prospectively collects a sample of risk-adjusted validated surgical patient data from >450 participating USA hospitals. The authors show that NAC was not an independent predictor of complications, reoperation, wound infection or dehiscence. The robustness of these findings is reinforced by the shorter adjusted length of stay among patients receiving NAC. Given that scant data exists on this topic, the authors contribute a valuable paper that substantially adds to the literature.

Despite its strengths, the study should be interpreted in light of notable limitations that the authors acknowledge. Many crucial variables are not tracked by the NSQIP and therefore cannot be accounted for, including type of chemotherapy regimen, delay between chemotherapy and surgery, surgical technique (open, laparoscopic, robotic), surgical quality (margins, extent of lymphadenectomy), clinical/pathological stage of bladder cancer, and hospital/surgeon volume. Besides, because RC is a morbid procedure with a mean length of stay of 11 days, 30-day complication rates do not capture its true morbidity as well as 90-day rates. In particular, several common complications, such as postoperative ileus or small bowel obstruction, tend to occur later during the postoperative recovery period. As such, chances are that the event rate is biased downward by the short-term duration of data capture by the NSQIP. This study also cannot fully examine the association of NAC with certain subtypes of complications, including gastrointestinal or bleeding complications, especially when other investigators examining robotic RC have reported a conflicting increase in perioperative complications associated with NAC [6] driven by a 27% rate of gastrointestinal complications, which are not tracked by the NSQIP. Of note, unadjusted rates of transfusion and bleeding events were both higher in the NAC group in the present study.

One of the relevant and heartening observations of the report is the gradual increase in the use of NAC over the study period from 4% of eligible patients to 11%, close to the NCDB estimates of 7.6% in 2006 to 20.9% in 2010 (P < 0.01) [3]. Interestingly, there was an increased probability of any complication in the most recent time period (odds ratio 0.47 for 2005–2009 relative to 2010–2011 in the primary multivariate model, P < 0.001). A plausible explanation is that as physicians have heeded the message to increase usage of NAC, treatment has expanded into a wider population with more comorbidities and therefore a greater propensity for complications. It would have been of interest to address this point by restricting the analyses to the most recent data to see if NAC does indeed predict perioperative complications in the most recent period from 2010 to 2011.

Finally, given the lack of detail available in the NSQIP, other relevant questions could not be addressed. Among them it would be relevant to know if complication rates vary between standard MVAC (methotrexate, vinblastine, doxorubicin and cisplatin) and newer chemotherapy regimens such as dose dense MVAC (DD-MVAC) or gemcitabine plus cisplatin (GC). Similarly, the role of the delay or the elapsed time between chemotherapy and surgery on complications might be helpful in future trial planning.

Additional work still needs to be done to identify prognostic factors for both perioperative complications and long-term outcomes after NAC, so that this valuable therapy can be appropriately provided to the correct patients. Indeed, given the lack of randomised controlled trial data investigating less toxic regimens than MVAC, perhaps NAC is underused because clinicians and patients are underserved by the available data. The authors should be commended for their efforts in deconstructing possible barriers to increased uptake of NAC, a therapy known to confer survival benefits for our patients with bladder cancer.

Joaquim Bellmunt,* Jeffrey J.Leow and William Martin-Doyle§
*Bladder Cancer Center, Dana-Farber/Brigham and Women’s Cancer Center, Boston, MA, USA; University Hospital Del Mar-IMIM, Barcelona, Spain; Brigham and Women’s Hospital, Division of Urology and Center for Surgery and Public Health, Boston, MA, USA; §University of Massachusetts Medical School, Worcester, MA, USA

Read the full article

References

  1. Johnson DC, Nielsen ME, Matthews J et al. Neoadjuvant chemotherapy for bladder cancer does not increase risk of perioperative morbidity. BJU Int 2014; 114: 221–228
  2. Bellmunt J, Orsola A, Wiegel T et al. Bladder cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. ESMO Guidelines Working Group. Ann Oncol 2011; 22 (Suppl. 6): 45–49
  3. Zaid HB, Patel SG, Stimson CJ et al. Trends in the utilization of neoadjuvant chemotherapy in muscle-invasive bladder cancer: results from the National Cancer Database. Urology 2014; 83: 75–80
  4. Meeks JJ, Bellmunt J, Bochner BH et al. A systematic review of neoadjuvant and adjuvant chemotherapy for muscle-invasive bladder cancer. Eur Urol 2012; 62: 523–533
  5. Millikan R, Dinney C, Swanson D et al. Integrated therapy for locally advanced bladder cancer: final report of a randomized trial of cystectomy plus adjuvant M-VAC versus cystectomy with both preoperative and postoperative M-VAC. J Clin Oncol 2001; 19: 4005–4013
  6. Johar RS, Hayn MH, Stegemann AP et al. Complications after robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium. Eur Urol 2013; 64: 52–57
Read more articles of the week

Video: Time to increase use of multimodal therapy in bladder cancer

Neoadjuvant chemotherapy for bladder cancer does not increase risk of perioperative morbidity

David C. Johnson*, Matthew E. Nielsen*†‡, Jonathan Matthews*, Michael E. Woods*, Eric M. Wallen*, Raj S. Pruthi*, Matthew I. Milowsky*†§ and Angela B. Smith*

*Department of Urology, University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, Cancer Outcomes Research Group, Multidisciplinary Genitourinary Oncology, Department of Epidemiology, Gillings School of Global Public Health, and §Department of Medicine, Division of Hematology/Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Read the full article
OBJECTIVE

To determine whether neoadjuvant chemotherapy (NAC) is a predictor of postoperative complications, length of stay (LOS), or operating time after radical cystectomy (RC) for bladder cancer.

PATIENTS AND METHODS

A retrospective review of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was performed to identify patients receiving NAC before RC from 2005 to 2011. Bivariable and multivariable analyses were used to determine whether NAC was associated with 30-day perioperative outcomes, e.g. complications, LOS, and operating time.

RESULTS

Of the 878 patients who underwent RC for bladder cancer in our study, 78 (8.9%) received NAC. Excluding those patients who were ineligible for NAC due to renal insufficiency, 78/642 (12.1%) received NAC. In all, 457 of the 878 patients (52.1%) undergoing RC had at least one complication ≤30 days of RC, including 43 of 78 patients (55.1%) who received NAC and 414 of 800 patients (51.8%) who did not (P = 0.58). On multivariable logistic regression, NAC was not a predictor of complications (P = 0.87), re-operation (P = 0.16), wound infection (P = 0.32), or wound dehiscence (P = 0.32). Using multiple linear regression, NAC was not a predictor of increased operating time (P = 0.24), and patients undergoing NAC had a decreased LOS (P = 0.02).

CONCLUSIONS

Our study is the first large multi-institutional analysis specifically comparing complications after RC with and without NAC. Using a nationally validated, prospectively maintained database specifically designed to measure perioperative outcomes, we found no increase in perioperative complications or surgical morbidity with NAC. Considering these findings and the well-established overall survival benefit over surgery alone, efforts are needed to improve the uptake of NAC.

Read more articles of the week

#UroJC July 2014 – Is there a place for laser techniques in our current schema of bladder cancer diagnosis and management?

This month’s International Urology Journal Club (@iurojc) truly engaged a global audience with participants from ten countries including author Thomas Herrman (@trwhermann) from Hannover, Germany.  A landmark 2000 followers was reached during July, nearly two years since @iurojc’s conception in late 2012. In fact, since this time nearly 1100 people have participated in the journal club from around the world.

Bladder cancer was up for debate for the first time this year and @iurojc trialled the discussion of two complementary articles recently published online ahead of print in the World Journal of Urology.  The first article provided an update of the current evidence for transurethral Ho:YAG and Tm:YAG in the endoscopic treatment of bladder cancer, and the second was a randomised controlled trial (RCT) comparing laser to the gold standard transurethral resection of bladder tumour (TURBT).  Authorship groups were from Germany and China respectively; our Chinese authors unfortunately unable to join the dialogue due to restriction on all twitter activity in the country.

Initial conversation focussed on the methodology, results and limitations of the RCT, however this soon extended to a more general discussion around the current difficulties with the diagnosis and management of bladder cancer and the pros and cons of using laser for this purpose.  Key themes debated over the 48-hour period included the importance of accurate staging, current standards of TURBT, advantages of en bloc resection and the learning curve, cost and usefulness of laser technology.

Both studies reiterated one of the major goals outlined in the EAU guidelines for non-muscle invasive bladder cancer (NMIBC), to achieve correct staging with inclusion of detrusor muscle and complete resection of tumours.  This is important in limiting second resection and consequently has a resulting cost offset.  In the review article, only 3 studies commented on staging quality and another two commented that laser was suitable for staging but did not specify if detrusor muscle was identified.

@ChrisFilson and @CBayneMD expressed their concern over the RCT by Chen and Colleagues

@linton_kate astutely pointed out another limitation

and author of the review article @trwherrmann summed this up nicely

In the RCT by Chen et al. there was a significantly greater number of pT1 tumours detected with laser than TURBT, the authors suggested this might be due to better sampling.  It remains unclear if this would impact on management and this did not enter the arena for discussion during this @iurojc.

Many argued that TURBT techniques and practices should be optimised before newer techniques are introduced.

‘En bloc’ was touted as the new trendy word in endourology.  EAU guidelines recommend en bloc resection for smaller tumours.  The articles suggested that en bloc resection of bladder tumours should provide more accurate staging however conclusive data is missing to substantiate this in the current literature. 

@DrHWoo discussed potential advantages of the laser technique

@linton_kate pointed out that en bloc resection is not limited to the laser technique

Further to this, the lack of obturator nerve reflection with laser was emphasised in the RCT.  Obturator kick was noted during TURBT in 18 patients and none during laser resection, however none of these patients suffered bladder perforation.  The significance of this was debated and usefulness of obturator block in this context discussed.

The pendulum seemed to the swing out of favour of laser during the discussion, with several limitations outlined including reduced ability for re-resection, cost and the presence of a learning curve.

Regarding additional cost, the host rebutted

The flow of academic dialogue was interrupted midstream (pardon the pun) by a light-hearted discussion around the ergonomics of TURBT.

Below are some of the key take home messages that arose from the usual culprits in this month’s @iruojc discussion

Kindly author @trwherrmann invited us to his upcoming en bloc resection workshop.  Keep an eye out for this.

@iurojc would like to thank Prostate Cancer Prostatic Diseases who have kindly provided the prize for this month which is a 12 month on line subscription to the journal. @nickbrookMD’s made efforts to sway the vote his way.

Whilst usually the Best Tweet Prize is reserved for some incisive comment, the repeated complaints from @nickbrookMD for his failure to ever win the Best Tweet prize has seen for the first and final time that the @iurojc has bowed to pressure. Congratulations to @nickbrookMD for finally having made it with the above tweet.

If you haven’t tuned into @iurojc, follow future journal club discussions via the hashtag #urojc, on the first Sunday/Monday of each month. 

 

Dr Marnique Basto (@DrMarniqueB) is a USANZ trainee from Victoria who recently completed a Masters of Surgery in the health economics of robotic surgery and has an interest in SoMe in Urology.

 

 

 

 

© 2022 BJU International. All Rights Reserved.