Tag Archive for: #BladderCancer

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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

 

 

Further Randomised Controlled Trials are needed….No! say something original.

Capture“As we all know, prostate/kidney/bladder cancer is a common disease…” aaargh!!! Of course it is, that’s why you are writing about it and trying to get this piece of work into this journal and why everyone who reads it might be interested; because it is so important and common! If we all know it anyway why are you bothering to tell us this whilst wasting time and your word count and not getting on with presenting the actual research? Anyone who doesn’t know that prostate cancer is pretty common isn’t a doctor let alone a urologist. This is found more often than I can stand and got me thinking about all the other scientific catchphrases and tactics that serve more to irritate than inform.

Common1Common2Common3

As the BJUI associate editor for Innovation and one of the triage editors, I read around 600 BJUI submissions each year as part of my role. This is not to mention the additional manuscripts I formally review for this journal and others and there are certain phrases and statements that really just make my blood boil. Time and time again the same statements come up that are put into medical papers seemingly without any thought and which add nothing other than serving to irritate the editor, reviewer and reader.

The throwaway statement that “further randomised trials are needed” is often added to the end of limited observational and cohort studies, presumably by young researchers and almost never adds anything. Anyone who has ever been involved with a surgical RCT will know how challenging it is to set one up and run one, let alone recruit to one which is why so few exist and why so many have failed. Just saying more RCTs are needed without thought to why they haven’t already been carried out just frustrates the reader and shows a lack of true comprehension of the subject. Suggesting an valid alternative to an RCT however might actually get people thinking.

Further1

So what else is in the wastebucket of things that cause journal irritation? Well conclusions that have no basis in the results that have been shown; such as XXX is a safe and generally acceptable procedure after 3 cases, of which one had a 2 litre blood loss; or we advise everyone to switch to our technique on the basis of this uncontrolled retrospective cohort. Another is YY is the “Gold Standard” even though this is just opinion that is usually very outdated and this way of doing things was really only the standard approach 20 years ago!

Failure to acknowledge the study limitations is another area that particularly winds me up especially when the authors did a procedure one way 500 times then subsequently did it 50 times in a subtly different way and state that the second is better without mentioning that they might have learnt a fair bit from the previous huge number of cases!

So please let me know what irritates you in a paper so I can watch out for it and makes sure never to use it myself

 

Ben Challacombe
Associate Editor, BJUI 

 

RSM Bladder Day

CaptureThe urology section of the RSM left Wimpole Street and travelled up to sunny Queen Elizabeth Hospital in Birmingham on the 24th April to be educated in the ‘Management of Non-Muscle invasive and Muscle Invasive Bladder Cancer’. This meeting was organised in collaboration with Nick James and Rik Bryan at the Birmingham Warwick Uro-Oncology unit as the RSM looks to add to its regional programme of teaching days.

The meeting was well attended by both experts as well as trainees and we kicked off with John McGrath and a review of the evidence behind current haematuria investigations as well as the new NICE guidelines. Professor Charles Hutchinson from the University of Warwick then gave a detailed talk on pre-operative imaging in bladder cancer and this led to an interesting debate on the necessity of performing a full TURBT in cases of known muscle invasive disease if the patient will ultimately require a cystectomy. No consensus was reached although if definitely proceeding to cystectomy it is unlikely to be beneficial. If radiotherapy is considered then debulking is important.

Eva Comperat from the Service d’Anatomie and Cytologie Pathologiques du Pr Capron presented a fascinating histopathological perspective of bladder cancer and it was interesting to see that even amongst eminent pathologists there can be challenges in distinguishing pTa from pT1 disease with only 44% in one large study showing full agreement. The importance in reporting histological variants such as micropapillary or plasmocytoid was discussed due to the aggressive nature of these types and the need for more radical treatment. This was also re-iterated by Peter Rimington while discussing early cystectomy which should be offered to all suitable patients at high risk of progression according to EORTC tables, especially in young patients and in tumours which are multifocal, difficult to resect, have deep lamina propria or prostatic involvement and those with associated CIS.

A highlight for me was Professor John Kelly’s talk on the treatment option of hyperthermic Mitomycin C. HYMN Trial.

Data from the HYMN trial which looked at hyperthermic MMC vs. standard treatment in BCG failures was disappointing in that there was no difference in terms of disease free survival at 24 months. Outcomes were found to be worse in patients with CIS, but in patients with papillary disease, hyperthermic MMC had far more favourable results. This has led to the HIVEC I and HIVEC II trials currently recruiting in the UK and Spain looking at standard MMC vs. hyperthermic MMC in intermediate risk disease. It was also interesting to see new immunotherapy drugs currently in phase III trials which will hopefully be available in the near future.

Rik Bryan’s presentation on the evolving role of bio markers explained that the Bladder Cancer Diagnostic Programme had found that contrary to our beliefs, patients trust, and would rather accept certainty over burden and thus would rather continue with cystoscopic surveillance over bio-markers, unless the sensitivity of these bio-markers was over 99%. No such bio-marker has yet been found to be that accurate but current research into odor-readers, urinary dipsticks and DNA all look promising in terms of potential for both diagnosis and prognosis.

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Both Nick James and Hugh Mostafid highlighted current research trials with the CALIBER RCT on chemo resection in recurrent low risk bladder cancer as well as the PHOTO trial looking at both clinical and cost effectiveness of photo-dynamic cystoscopy leading the way in terms of surgical trials currently recruiting. Nick also caused a stir on Twitter as he presented data showing a median survival advantage of more than a year between surgeons performing low or high volume of cystectomies annually. Surely we do not need more convincing evidence to centralise such surgery?

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Reviewing bladder cancer from the oncologist’s perspective, Syed Hussein from the University of Liverpool explained that although there is a 6% overall survival benefit with neo-adjuvant chemotherapy there have been no RCT on MVAC vs gemcitabine/cisplatin regimes. Nick James’ talk on bladder preserving treatment added to this that synchronous chemoradiotherapy could be complementary to neo-adjuvant treatment and the addition of synchronous chemotherapy has been shown to provide a significant improvement in terms of loco regional control.

Vijay Ramani presented his series on salvage cystectomy with no significant difference in terms of complications for salvage vs. primary surgery as long as certain techniques were adopted such as division of ureters outside of the pelvis and using bowel at least 15-20cm proximal from the ileocaecal valve.

To complete the diverse and stimulating programme, Professor Peter Wiklund from the Karolinska University Hospital, Stockholm, presented a state of the art lecture on “Reconstruction rules! The robot has taken over?”. With discussion and impressive videos demonstrating intra-corporeal robotic neobladder reconstruction it was difficult not to be in awe of such an impressive series, with a 90% continence rate in males.

Overall it was fantastic to have the RSM in the West Midlands. Roger Plail has done much to reach out to those of us outside of London and I look forward to the Geoffrey Chisholm Prize Meeting and AGM on the 22nd May in Hastings. RSM President’s Day.

Rebecca Tregunna, Speciality Trainee, Burton Hospitals NHS Foundation Trust, West Midlands Deanery @RebeccaTregunna

 

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

 

Editorial: Robotic and conventional open radical cystectomy lead to similar postoperative health-related quality of life

In this month’s issue of BJU International, Messer et al. [1] devise a prospective randomised trial to compare postoperative health-related quality of life (HRQoL) after robot-assisted (RARC) vs conventional open radical cystectomy (ORC). The investigators evaluated 40 patients over a follow-up period of 1 year and found no significant difference in HRQoL between surgical approaches. Moreover, they showed that the postoperative decrease in HRQoL returns to baseline within 3 months of surgery.

RC is one of the most challenging and potentially mutilating surgical interventions in the urological field and represents the standard-of-care treatment for patients with muscle-invasive bladder cancer. It is associated with a non-negligible risk of morbidity and mortality [2]. With the advent of new technologies, such as the Da Vinci surgical robot, carefully designed studies are needed to weigh the potential benefits of a novel approach against the increased costs associated with such tools. While RARC holds the promise of combining the benefits of a minimally invasive intervention with the precise robotic translation of the surgeon’s movements, these claims remain to be definitely proven in the clinical setting. As such, further elucidating the effect of surgical approach on perioperative outcomes after RC is essential for treatment planning, patient counselling and informed decision-making before surgery.

QoL is increasingly used as a quantitative measure of treatment success [3, 4]. These measures are gaining considerable traction in the USA, as reimbursements will soon be tied to patient satisfaction. While previous retrospective studies suggest that RARC has comparable perioperative oncological outcomes with potentially lower morbidity relative to ORC [5], there is a scarcity of high-quality evidence on HRQoL outcomes of RARC vs ORC. The difficulties of conducting randomised trials in the surgical setting are reflected by the relatively few participants in the Messer et al. [1] trial. Nonetheless, in their pilot study, the authors demonstrated the feasibility of a HRQoL trial in RC patients. Furthermore, they deliver initial evidence on the impact of surgical approach on HRQoL after RC.

From a clinical perspective, the authors contribute interesting findings to the ongoing debate. Their results suggest that the potential benefits of robot-assisted surgery on HRQoL may be limited in patients undergoing complex oncological surgery such as RC. Several hypotheses may be pertinent to their conclusions. For example, performing an open urinary diversion after RARC that can take as much time as the actual extirpative RC may mitigate any potential benefit of the minimally invasive approach. Furthermore, the study findings may be largely influenced by the surgical skills of the participating surgeons. Maybe the correct interpretation of their study findings is that there was no significant difference in HRQoL outcomes between ORC and RARC, at the institution where the trial was performed.

Nonetheless, the authors suitably demonstrate the feasibility of performing a randomised trial in this field and pave the way towards adequately powered, randomised multicentre trials that can provide further evidence on what impact RARC may have on perioperative outcomes and beyond.

Read the full article

Julian Hanske, Florian Roghmann, Joachim Noldus and Quoc-Dien Trinh*

Department of Urology, Marien Hospital, Ruhr-University Bochum, Herne, Germany, and *Division of Urologic Surgery and Center for Surgery and Public Health, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

References

1 Messer JC, Punnen S, Fitzgerald J, Svatek R, Parekh DJ. Health-related quality of life from a prospective randomised clinical trial of robot-assisted laparoscopic vs open radical cystectomy. BJU Int 2014; 114: 896–902

2 Roghmann F, Trinh QD, Braun K et al. Standardized assessment of complications in a contemporary series of European patients undergoing radical cystectomy. Int J Urol 2014; 21: 143–9

3 Cookson MS, Dutta SC, Chang SS, Clark T, Smith JA Jr, Wells N. Health related quality of life in patients treated with radical cystectomy and urinary diversion for urothelial carcinoma of the bladder: development and validation of a new disease specific questionnaire. J Urol 2003; 170: 1926–30

4 Loppenberg B, von Bodman C, Brock M, Roghmann F, Noldus J, Palisaar RJ. Effect of perioperative complications and functional outcomes on health-related quality of life after radical prostatectomy. Qual Life Res 2014. doi: 10.1007/s11136-014-0729-1

5 Kader AK, Richards KA, Krane LS, Pettus JA, Smith JJ, Hemal AK. Robot-assisted laparoscopic vs open radical cystectomy: comparison of complications and periopera

 

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
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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

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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.

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#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.

 

 

 

 

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