Tag: radical cystectomy

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Editorial: Should we care more about SPARE?

November 8, 2017/by admin Z.9

Huddart et al. [1] report the results of a phase III clinical trial (SPARE) evaluating the feasibility of randomising participants with cT2/T3 muscle-invasive bladder cancer (MIBC) to either radiation or radical cystectomy (RC) following neoadjuvant chemotherapy. Whilst attempting to address an important, in fact crucial ongoing point of debate, due to poor patient accrual (45 participants recruited in 30 months) the study was terminated early. Additionally, compliance with study assignment was low, with as many as 24% of participants electing to proceed with a treatment arm that was the opposite of what they were randomised to. This underscores the problems with obtaining randomised data in an era where patient and clinician preference drive clinical decision-making.

Whilst well-performed prospective studies show acceptable results with bladder-sparing approaches (69% complete response and 71% 5-year disease-specific survival [2]), no randomised clinical trials comparing bladder sparing with RC have demonstrated equivocal results. As non-randomised studies are subject to selection bias [many patients with large bulky T3 tumours or those with carcinoma in situ (CIS) or hydronephrosis have not met inclusion criteria for trials of bladder sparing], it is often debated as to whether bladder sparing is appropriate for the entire population of patients with MIBC or a selected subset. This is especially important in a deadly disease such as bladder cancer, where we often have only one chance to get it right and hence recent guidelines state that bladder sparing and radical options should be discussed with the patient.

Whilst we acknowledge the limitations based on the number of participants analysed, these data show some interesting trends [1]. There appears to be more local recurrence with radiation therapy (69%) compared to RC (15%), this despite confirmation of ≤cT1 disease after neoadjuvant chemotherapy. And while most of the local failures are attributed to non-muscle-invasive recurrences; additional treatments, patient anxiety, and potential salvage RC, as well as the cost of surveillance, must be considered in reflecting on these results. It is unclear whether these factors are outweighed by the perceived lower toxicity in these patients.

It is our opinion that until randomised studies show equivalency, radiation-based approaches should definitely be discussed with all patients but patients should also be guided as to who are ideal candidates. Ideal candidates are those who have non-variant histology (pure urothelial carcinoma), non-bulky (minimal) invasive T2 cancer, absence of CIS, absence of a three-dimensional mass on imaging or examination, absence of hydronephrosis, and have an adequate bladder capacity [3]. The role of multidisciplinary care is paramount, maximal transurethral resection is a critical initial step, as incomplete resections can potentially double the odds of eventual RC in bladder-sparing protocols [4]. Additionally, concomitant chemotherapy has shown improved survival and should be considered standard of care based on a randomised control trial [5]. The addition of neoadjuvant chemotherapy is unknown and needs to be further evaluated. In addition to the treatment itself, it is clear that vigilant surveillance is critical in identifying patients at highest risk of failure and requires a combination of both cystoscopy and imaging, with expedient salvage RC.

Beyond the challenges of treating patients with MIBC, this report from Huddart et al. [1] reflects the larger issue of clinical trial accrual. As mentioned, patients and clinicians often have predetermined notions about the ‘best’ course of action, even in the context of a randomised clinical trial. These limitations have plagued early closure of other trials in bladder cancer as well. Similarly in prostate cancer, comparative treatment trials of radiation and surgery are limited as patients are reluctant to relinquish decisions about their treatment. Clearly, an intensive effort is necessary to create clinical trials that are palatable to a multi-disciplinary treatment team committed to answering tough therapy questions. MIBC is no different, where we often offer differing treatment modalities without having quality comparative data, which is a disservice to our patients who look to us to guide their treatment approaches based on best available hard evidence. We again commend the authors for their well-designed clinical trial and presenting their results and challenges from the SPARE trial.

Eugene K. Lee* and Ashish M. Kamat†

*University of Kansas Medical Center, Kansas City, KS and † Department of Urology, MD Anderson Cancer Center, Houston, TX, USA

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References

1 Huddart RA, Birtle A, Maynard L et al. Clinical and patient-reported outcomes of SPARE – a randomised feasibility study of selective bladder preservation versus radical cystectomy. BJU Int 2017; 120: 639–50

2 Mak RH, Hunt D, Shipley WU et al. Long-term outcomes in patients with muscle-invasive bladder cancer after selective bladder-preserving combined-modality therapy: a pooled analysis of Radiation Therapy Oncology Group protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol 2014; 32: 3801–9

3 Smelser WW, Austenfeld MA, Holzbeierlein JM, Lee EK. Where are we with bladder preservation for muscle-invasive bladder cancer in 2017? Indian J Urol 2017; 33: 111–17

4 Efstathiou JA, Spiegel DY, Shipley WU et al. Long-term outcomes of selective bladder preservation by combined-modality therapy for invasive bladder cancer: the MGH experience. Eur Urol 2012; 61: 705–11

5 James ND, Hussain SA, Hall E et al. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med 2012; 366: 1477–88

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

June 21, 2017/by admin Z.9

Every week the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

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

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

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

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

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How to Cite

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

Abstract

Objectives

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

Patients and methods

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

Results

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

Conclusion

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

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

June 21, 2017/by Michael Koch

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

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

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Michael O. Koch, Chairman and Professor of Urology

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

Reference

1 Soave A, Riethdorf S, Dahlem R et al. Detection and oncological effect of circulating tumour cells in patients with variant urothelial carcinoma histology treated with radical cystectomy. BJU Int 2017; 119: 854–61

Article of the Week: Risk Factors and Timing of VTE after RC

November 16, 2016/by admin Z.9

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.

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

Risk factors and timing of venous thromboembolism after radical cystectomy in routine clinical practice: a population-based study

R. Christopher Doiron*, Christopher M. Booth†,‡,§, Xuejiao Wei§ and D. Robert Siemens*,†,§

*Department of Urology, Queen’s University, Kingston, ON, Canada, †Department of Oncology, Queen’s University, ‡Department of Public Health Sciences, Queen’s University, and §Division of Cancer Care and Epidemiology, Queen’s University Cancer Research Institute, Kingston, ON, Canada

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Objective

To describe the risk factors and timing of perioperative venous thromboembolism (VTE) and its association with survival for patients undergoing radical cystectomy (RC) in routine clinical practice.

Patients and Methods

The population-based Ontario Cancer Registry was linked to electronic records of treatment to identify all patients who underwent RC between 1994 and 2008; VTE events were identified from hospital diagnostic codes. Multivariate logistic regression analysis was used to determine the factors associated with perioperative VTE. A Cox proportional hazards regression model explored the associations between VTE and survival.

Results

Of the 3 879 patients included in the study, 3.6% (141 patients) were diagnosed with VTE at ≤1 month of their surgical admission date. This increased to 4.7% (181) at ≤2 months and 5.4% (211) at ≤3 months. In all, 55% of VTE events presented after hospital discharge. In multivariate analysis, factors associated with VTE included higher surgeon volume (P = 0.004) and increased length of hospital stay (LOS; P< 0.001). Lymph node yield and adjuvant chemotherapy were not associated with VTE. VTE was associated with an inferior cancer-specific survival [hazard ratio (HR) 1.35, 95% confidence interval (CI) 1.13–1.62] and overall survival (HR 1.27, 95% CI 1.08–1.49).

Conclusions

Over half of VTE events in RC patients occur after hospital discharge, with a substantial incidence up to 3 months after surgery. Limited actionable risk factors for VTE were identified other than LOS. In this population-based cohort, VTE was associated with inferior long-term survival.

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Editorial: RC & VTE – Are We Doing Enough?

November 16, 2016/by Nawar Hanna

Using a large comprehensive population-based cohort from Canada, Doiron et al. [1] present an in-depth analysis of risk factors and timing of venous thromboembolism (VTE) after radical cystectomy (RC) for bladder cancer. This report reiterates what is already known, which is that VTE after RC occurs at a non-negligible rate (5.4%) and most VTEs occur after hospital discharge (55%). VTE is an established complication in patients undergoing major oncological surgery, with some guidelines recommending 4 weeks of VTE prophylaxis after major pelvic surgery. This significant incidence of VTE after discharge highlights the potential impact of extended VTE prophylaxis for up to 28 days. Level I evidence for such practice was published more than a decade ago [2]. Yet, the uptake of these data remains low, at least in urological oncology. A recent survey-based study of pelvic cancer centres from the UK showed that only two-thirds of centres use post-discharge prophylaxis [3]. Using highly granular data, Doiron et al. [1] provide a detailed timeline of VTE occurrence after RC. They found that among patients who were diagnosed with VTE after discharge, >60% of these events occurred at ≤4 weeks of discharge. Unfortunately, there were no data on whether VTE prophylaxis was used in the study population.

The authors identified greater surgeon volume and increased length of hospital stay as risk factors for postoperative VTE, while accounting for important disease-related covariates. As mentioned by the authors, surgeon volume is most likely a surrogate for another unmeasured confounder. Higher volume surgeons, who often practice in large/academic institutions, may have increased case complexity with patients at higher risk for VTE. Additionally, such institutions may be more prone to perform diagnostic testing in high-risk patients and identify VTEs that would have otherwise gone unnoticed. A report from France found that the rate of VTE after RC was 24% in a cohort of patients who all underwent complete lower limb ultrasound, yet the vast majority (92%) were asymptomatic [4]. In other words, if you are looking for a VTE, you are more likely to find one. However, the clinical relevance of these VTEs remains unclear.

As shown from prior studies, length of stay was also found to be a risk factor for VTEs. Why does an increase in length of stay lead to a higher rate of VTE? One explanation is that patients who stay in the hospital longer are more likely to be immobilised for longer. This may explain why patients undergoing RC have higher rates of VTE than those undergoing other urological oncology procedures. However, immobilisation is a difficult variable to define or to measure. If longer immobilisation leads to increased VTE incidence, recently implemented enhanced recovery after surgery (ERAS) protocols that lead to earlier mobilisation would be expected to be associated with fewer VTEs. It is important to mention that other previously associated factors with VTE, including operative time and body mass index, which may be related to immobilisation time are not recorded in this study.

The use of neoadjuvant chemotherapy (NACT) for muscle-invasive bladder cancer has been shown to improve overall survival and is being increasingly used in RC patients. This study examined NACT as a risk factor but did not find an association. Notably, they were limited by the few patients who had received NACT. The use of chemotherapy in patients with cancer is a well-recognised risk factor for VTE [5]. It will be important in the future to continue to examine the incidence of VTE in NACT patients as this population grows.

Taken together, patients undergoing major cancer surgery have a significant risk of postoperative VTE, with evidence showing that rates of VTE are increasing over time [6]. Although guidelines for VTE prophylaxis are not uniform, this study’s findings [1] that most VTEs occur after discharge is a reason for urological surgeons to strongly consider extended VTE prophylaxis in this high-risk population.

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Nawar Hanna and Jacqueline M. Speed

Division of Urological Surgery and Center for Surgery and Public Health, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

References

1 Doiron RC, Booth CM, Wei X, Siemens DR. Risk factors and timing of venous thromboembolism after radical cystectomy in routine clinical practice: a population-based study. BJU Int 2016; 118: 714–22

2 Bergqvist D, Agnelli G, Cohen AT et al. Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. N Engl J Med 2002; 346: 975–80

3 Pridgeon S, Allchorne P, Turner B, Peters J, Green J. Venous thromboembolism (VTE) prophylaxis and urological pelvic cancer surgery: a UK national audit. BJU Int 2015; 115: 223–9

4 Clement C, Rossi P, Aissi K et al. Incidence, risk proﬁle and morphological pattern of lower extremity venous thromboembolism after urological cancer surgery. J Urol 2011; 186: 2293–7

5 Blom JW, Vanderschoot JPM, Oostindier MJ, Osanto S, van der Meer FJM, Rosendaal FR. Incidence of venous thrombosis in a large cohort of 66,329 cancer patients: results of a record linkage study. J Thromb Haemost 2006; 4: 529–35

6 Trinh VQ, Karakiewicz PI, Sammon J et al. Venous thromboembolism after major cancer surgery: temporal trends and patterns of care. JAMA Surg 2014; 149: 43–9

Article of the Week: Complications and QoL in patients undergoing CU with single stoma or IC after RC

October 26, 2016/by admin Z.9

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.

Complications and quality of life in elderly patients with several comorbidities undergoing cutaneous ureterostomy with single stoma or ileal conduit after radical cystectomy

Nicola Longo*, Ciro Imbimbo*, Ferdinando Fusco*, Vincenzo Ficarra†, Francesco Mangiapia*, Giuseppe Di Lorenzo‡, Massimiliano Creta§, Vittorio Imperatore§ and Vincenzo Mirone*

*Department of Neurosciences, Sciences of Reproduction and Odontostomatology, University Federico II of Naples, Naples, †Urology Department, University of Udine, Udine, ‡Oncology Department, University Federico II of Naples, and §Urology Unit, Buon Consiglio Fatebenefratelli Hospital, Naples, Italy

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Objectives

To compare peri-operative outcomes and quality of life (QoL) in a series of elderly patients with high comorbidity status who underwent single stoma cutaneous ureterostomy (CU) or ileal conduit (IC) after radical cystectomy (RC).

Patients and Methods

The clinical records of patients aged >75 years with an American Society of Anesthesiologists (ASA) score >2 who underwent RC at a single institution between March 2009 and March 2014 were retrospectively analysed. After RC, all patients included in the study received an IC urinary diversion or a CU with single stoma urinary diversion. Preoperative clinical characteristics as well as intra- and postoperative outcomes were evaluated and compared between the two groups. In addition, the Bladder Cancer Index (BCI) was used to assess QoL.

Results

A total of 70 patients were included in the final comparative analyses. Of these, 35 underwent IC diversion and 35 CU single stoma diversion. The two groups were similar with regard to age, gender, ASA score, type of indication and pathological features. Operating times (P < 0.001), estimated blood loss (P < 0.001), need for intensive care unit stay (P = 0.01), time to drain removal (P < 0.001) and length of hospital stay (P < 0.001) were significantly higher in patients undergoing IC diversion. The number of patients with intra- (P = 0.04) and early postoperative (P = 0.02) complications was also significantly higher among those undergoing IC diversion. Interestingly, the mean BCI scores were overlapping in the two groups.

Conclusions

The present results show that CU with a single stoma can represent a valid alternative to IC in elderly patients with relevant comorbidities, reducing peri-operative complications without a significant impairment of QoL.

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Editorial: Cutaneous Ureterostomy: ‘Back to the Future’

October 26, 2016/by Fiona Burkhard

An increasingly ageing and frail population undergoing cystectomy and urinary diversion has rekindled interest in urinary diversions with a lower risk of peri-operative complications, such as cutaneous ureterostomy (CU).

The study in this issue of BJUI by Longo et al. [1] compares complications and quality of life in elderly patients with high comorbidities (American Society of Anesthesiologists [ASA] physical status score 3–4 and Charlson Comorbidity Index [CCI] ~5) receiving either an ileal conduit (IC) or a CU with a single stoma. Although the IC group had longer surgery, greater intra-operative blood loss, a higher number of patients needing intensive care monitoring, a longer time to drain removal and a longer hospital stay, as well as a higher number of intra- and early postoperative complications, the intensive care unit length of stay and quality of life did not differ.

Complication rates are high for cystectomy and urinary diversion, especially in the frail elderly population with comorbidities [2]. Most studies are retrospective and the reported complication rates differ largely. Few centres have compared IC with CU and, probably as a result of selection biases, the results vary [3, 4]. Obvious advantages of CU are the reduced length of surgery and the lack of a bowel anastomosis, and peritoneal lesions can be minimized or omitted, thus reducing the risk of postoperative ileus (POI), a common complication after urinary diversion. These advantages were confirmed in the present study, with prolonged POI observed in 25.7% in the IC group vs 5.7% in the CU group and the duration of surgery being 226 min in the IC group vs 150 min in the CU group. Interestingly, there was no difference in major complications classified as Clavien–Dindo grades III–IV, with the exception of urinary leakage from the uretero-ileal anastomosis (14.2%).

Somewhat surprisingly, 42.8% of patients with IC required a blood transfusion compared with 17.1% with UC. The main blood loss usually takes place during cystectomy, whereas blood loss during urinary diversion is minimal [5]. The authors explain this through bleeding from the mesenteric vessels associated with isolating a bowel segment for IC, an occurrence not commonly observed in our experience or in other published reports. Overall the transfusion rate seems high, but this is highly dependent on the preoperative haemoglobin level/anaemia and the haemoglobin level set for transfusion, which differs between centres.

One of the main problems with CU is ureteric obstruction, especially of the left ureter. The rationale behind this is the more extensive mobilization of the left ureter to enable its transfer to the right side, which can result in ischaemic lesions of the distal ureter. Stenosis and kinking of the ureters when passing through the abdominal wall can also lead to obstruction. For these reasons, many patients have long-term ureteric stents. In the present study, the ureteric stents were changed every month. Foreign bodies in the urinary tract can cause problems such as upper urinary tract infections, stent encrustation and nephrolithiasis [3]. To reduce these problems, meticulous care of the CU and frequent changes of the silicone JJ stent with antibiotic prophylaxis are generally recommended. A cost assessment would be of interest to determine the long-term cost of regular stent changes compared with the management of a higher rate of peri-operative complications in patients receiving an IC. Tubeless approaches have been described, and one study reported less ureteric obstruction with deferred stent removal after surgery [6].

The Bladder Cancer Index score as a measure of quality of life did not differ between groups. Quality of life questionnaires assessing urinary diversion have inherent problems. When comparing leakage (frequency of leakage) and control (amount of leakage) in a patient with an IC or a CU, it is not surprising that there is no difference. However, the need for regular hospital visits to change the stents, which can be bothersome for patients, especially the frail and dependent elderly or those with problems travelling, because of the need to transport the necessary aides (stoma bags, pads, catheters), are rarely addressed in questionnaires.

Cutaneous ureterostomy, which is being rediscovered, belongs in the armamentarium of every surgeon performing cystectomy. However, each type of urinary diversion has its pros and cons, and careful selection is necessary to balance benefits against risks in an effort to offer the best individual option to the older and frail patient.

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Fiona C. Burkhard* and Patrick Y. Wuethrich†

*Department of Urology, University Hospital Bern, Inselspital Anna Seiler-Haus, Bern, Switzerland and †Department of Anaesthesiology and Pain Medicine, University Hospital Bern, Bern, Switzerland

References

1 Longo N, Imbimbo C, Fusco F et al. Complications and quality of life in elderly patients with several comorbidities undergoing cutaneous ureterostomy with single stoma or ileal conduit after radical cystectomy. BJU Int 2016; 118: 521–6

2 Izquierdo L, Peri L, Leon P et al. The role of cystectomy in elderly patients – a multicentre analysis. BJU Int 2015; 116(Suppl 3): 73–9

3 Deliveliotis C, Papatsoris A, Chrisofos M et al. Urinary diversion in high-risk elderly patients: modiﬁed cutaneous ureterostomy or ileal conduit? Urology 2005; 66: 299–304

4 Kilciler M, Bedir S, Erdemir F et al. Comparison of ileal conduit and transureteroureterostomy with ureterocutaneostomy urinary diversion. Urol Int 2006; 77: 245–50

5 Wuethrich PY, Studer UE, Thalmann GN et al. Intraoperative continuous norepinephrine infusion combined with restrictive deferred hydration signiﬁcantly reduces the need for blood transfusion in patients undergoing open radical cystectomy: results of a prospective randomised trial. Eur Urol 2014; 66: 352–60

6 Rodriguez AR, Lockhart A, King J et al. Cutaneous ureterostomy technique for adults and effects of ureteral stenting: an alternative to the ileal conduit. J Urol 2011; 186: 1939–43

Article of the Week: Using cardiopulmonary reserve to predict complications following radical cystectomy

April 29, 2015/by admin Z.9

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.

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

Cardiopulmonary Reserve as Determined by Cardiopulmonary Exercise Testing Correlates with Length of Stay and Predicts Complications following Radical Cystectomy

Stephen Tolchard, Johanna Angell, Mark Pyke, Simon Lewis, Nicholas Dodds, Alia Darweish, Paul White* and David Gillatt†

Departments of Anaesthesia and† Surgery, North Bristol NHS Trust, and *Applied Statistics Group, Department of Mathematics and Statistics, University of the West of England, Bristol, UK

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OBJECTIVES

To investigate whether poor preoperative cardiopulmonary reserve and comorbid state dictate high-risk status and can predict complications in patients undergoing radical cystectomy (RC).

PATIENTS AND METHODS

In all, 105 consecutive patients with transitional cell carcinoma (TCC; stage T1–T3) undergoing robot-assisted (38 patients) or open (67) RC in a single UK centre underwent preoperative cardiopulmonary exercise testing (CPET). Prospective primary outcome variables were all-cause complications and postoperative length of stay (LOS). Binary logistic regression analysis identified potential predictive factor(s) and the predictive accuracy of CPET for all-cause complications was examined using receiver operator characteristic (ROC) curve analysis. Correlations analysis employed Spearman’s rank correlation and group comparison, the Mann–Whitney U-test and Fisher’s exact test. Any relationships were confirmed using the Mantel–Haenszel common odds ratio estimate, Kaplan–Meier analysis and the chi-squared test.

RESULTS

The anaerobic threshold (AT) was negatively (r = −206, P = 0.035), and the ventilatory equivalent for carbon dioxide (VE/VCO₂) positively (r = 0.324, P = 0.001) correlated with complications and LOS. Logistic regression analysis identified low AT (<11 mL/kg/min), high VE/VC0₂ (≥33) and hypertension as significant factors, such that, in their presence patients were 5.55-times more likely to have complications at 90 days postoperatively [P = 0.001, 95% confidence interval (CI) 2.2–13.9]. ROC analysis showed a high significance (area under the curve 0.78, 95% CI 0.69–0.87; P < 0.001). In addition, based on CPET criteria >50% of patients presenting for RC had significant heart failure, whereas preoperatively only very few (2%) had this diagnosis. Analysis using the Mann–Whitney test showed that a VE/VCO₂ ≥33 was the most significant determinant of LOS (P = 0.004). Kaplan–Meier analysis showed that patients in this group had an additional median LOS of 4 days (P = 0.008). Finally, patients with an American Society of Anesthesiologists grade of 3 (ASA 3) and those on long-term β-blocker therapy were found to be at particular risk of myocardial infarction (MI) and death after RC with odds ratios of 4.0 (95% CI 1.05–15.2; P = 0.042) and 6.3 (95% CI 1.60–24.8; P = 0.008).

CONCLUSION

Patients with poor cardiopulmonary reserve and hypertension are at higher risk of postoperative complications and have increased LOS after RC. Heart failure is known to be a significant determinant of perioperative death and is significantly under diagnosed in this patient group.

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Editorial: Cardiopulmonary exercise testing: fortune-teller or guardian angel?

April 29, 2015/by John McGrath

In this month’s issue of BJUI, Tolchard et al. [1] describe their experience with the use of cardiopulmonary exercise testing (CPET) in patients undergoing radical cystectomy. In particular, they assess the value of cardiopulmonary reserve in predicting complications and the length of stay in hospital after surgery.

The origin of CPET is in non-surgical specialties for the further investigation of patients with cardiac failure or unexplained breathlessness [2], but it subsequently gained utility in surgical fields, including the preoperative assessment of patients undergoing cardiac surgery [3].

In more recent times, it has been increasingly adopted within ‘high-risk’ preoperative assessment clinics for those patients undergoing a wide range of major elective, non-cardiac surgery; however, this enthusiastic uptake has often preceded more formal validation of the test’s ability to perform reliably in these new patient groups and their associated surgical procedures. The Bristol group [1] has therefore prospectively studied the role of CPET in 105 patients undergoing either robot-assisted or open radical cystectomy for TCC, using all-cause complications and length of stay as the primary outcome variables.

The researchers found that anaerobic threshold (AT), ventilatory equivalent for carbon dioxide (VE/VCO₂) and hypertension were independent predictors of postoperative complications. Using the criteria chosen by Older et al. [4] of an AT ≤ 11 mL/kg/min and or VE/VECO₂ ≥ 33, it was possible to define a high- and low-risk group. The high-risk group were 5.5 times more likely to experience a complication at 90 days compared with the low-risk group and, notably, all deaths and myocardial infarctions occurred in the high-risk group. As expected, they found that complications prolonged length of stay. Additionally, falling AT and or rising VE/VECO₂ also correlated with increasing length of stay. Their study therefore suggests that CPET may have a role in the preoperative risk stratification of patients undergoing radical cystectomy by an open or robot-assisted approach.

The authors acknowledge that the cohort size is small and from a single institution, thereby necessitating further validation work across multiple centres, as well as subgroup analysis of differing surgical approaches. Interestingly, their study excluded patients who had received neoadjuvant chemotherapy; for many UK cancer centres, this would exclude ∼70% of patients undergoing radical cystectomy. It would clearly be important in future studies to understand how CPET metrics perform in this wider cohort, where anaemia and impaired performance status are known to be more common.

On the assumption that further studies may validate the use of CPET as a preoperative risk-stratifying tool, the pertinent question is how do we translate this research finding into patient benefit? Interventions such as preoperative patient optimization, pre-habilitation exercise regimes or the planned escalation of postoperative care may confer benefits but, as yet, we do not know if they attenuate the increased risk of complications or the prolonged inpatient stay.

As further evaluation of CPET takes place, we should remain cautious about its use as a ‘rule-out’ investigation in those patients otherwise considered eligible for radical surgical treatment. To date, there have been no formal evaluations of patients’ quality of life or end-of-life care in ‘non-operated’ cases. Poor local control of pelvic malignancy remains one of the most challenging aspects of care for uro-oncologists and, at times, it may even outweigh the impact of postoperative surgical complications. Due consideration must be given to this aspect when advising individual patients about the predicted risks and benefits of therapeutic treatment options. The decision to operate should clearly be informed by the preoperative assessment, but it is imperative that it continues to involve the patient’s wider multidisciplinary team, whose responsibility it will be to provide lifelong care.

In conclusion, CPET offers an interesting opportunity to identify those patients at greatest risk of adverse outcomes after radical cystectomy; however, the full benefits will not be realized if it is simply the ‘bearer of bad news’. The key to its success will be the identification of modifiable behaviours, by both the patient and the clinical team, that lead to improved patient-related outcomes. These outcomes should not be restricted to overall or cancer-specific survival but also measures of return to good health and prior performance status. Such longer-term outcome data may then help us to more accurately delineate the point at which the risks of a surgical treatment can be confidently predicted to outweigh the alternative of non-operative care for individual patients.

Read the full article

John S. McGrath

Royal Devon and Exeter NHS Trust, Exeter, UK

References

1 Tolchard S, Angell J, Pyke M et al. Cardiopulmonary reserve as determined by cardiopulmonary exercise testing correlates with length of stay and predicts complications following radical cystectomy. BJU Int 2014; [Epub ahead of print]. doi: 10.1111/bju.12895

2 Szlachcic J, Massie BM, Kramer BL, Topic N, Tubau J. Correlates and prognostic implication of exercise capacity in chronic congestive heart failure. Am J Cardiol 1985; 55: 1037–42

3 Mancini DM, Eisen H, Kussmaul W, Mull R, Edmunds LH Jr, Wilson JR. Value of peak exercise oxygen consumption for optimal timing of cardiac transplantation in ambulatory patients with heart failure. Circulation 1991;83: 778–86

4 Older P, Hall A, Hader R. Cardiopulmonary exercise testing as a screening test for perioperative management of major surgery in the elderly. Chest 1999; 116: 355–62

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

January 23, 2015/by Greg Nason

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