Tag Archive for: #BladderCancer

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Article of the month: Better QOL with orthotopic neobladders

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 a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from Dr. Singh of orthotopic neobladder reconstruction by sigmoid colon.

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

Prospective comparison of quality-of-life outcomes between ileal conduit urinary diversion and orthotopic neobladder reconstruction after radical cystectomy: a statistical model

Vishwajeet Singh, Rahul Yadav, Rahul Janak Sinha and Dheeraj Kumar Gupta
Department of Urology, King George Medical University, Lucknow, Uttar Pradesh, India

OBJECTIVE

• To conduct a prospective comparison of quality-of-life (QoL) outcomes in patients who underwent ileal conduit (IC) urinary diversion with those who underwent orthotopic neobladder (ONB) reconstruction after radical cystectomy for invasive bladder cancers.

PATIENTS AND METHODS

• Between January 2007 and December 2012, 227 patients underwent radical cystectomy and either IC urinary diversion or ONB (sigmoid or ileal) reconstruction.

• Contraindications for ON were impaired renal function (serum creatinine >2 mg/dL), chronic inflammatory bowel disease, previous bowel resection and tumour involvement at the bladder neck/prostatic urethra. Patients who did not have these contraindications chose to undergo either IC or ONB reconstruction, after impartial counselling.

• Baseline characteristics, including demographic profile, body mass index, comorbidities, histopathology of the cystoprostatectomy (with lymph nodes) specimen, pathological tumour stage, postoperative complications, adjuvant therapy and relapse, were recorded and compared.

• The European Organization for Research and Treatment of Cancer QoL questionnaire C30 version 3 was used to analyse QoL before surgery and 6, 12 and 18 months after surgery.

RESULTS

• Of the 227 patients, 28 patients in the IC group and 35 in the ONB group were excluded. The final analysis included 80 patients in the IC and 84 in the ONB group.

• None of the baseline characteristics were significantly different between the groups, except for age, but none of the baseline QoL variables were found to be correlated with age.

• In the preoperative phase, there were no significant differences in any of the QoL domains between the IC or the ONB groups. At 6, 12 and 18 months in the postoperative period, physical functioning (P < 0.001, P < 0.001 and P = 0.001, respectively), role functioning (P = 0.01, P = 0.01 and P = 0.003, respectively), social functioning (P = 0.01, P = 0.01 and P = 0.01, respectively) and global health status/QoL (P < 0.001, P < 0.001 and P = 0.002, respectively) were better in patients in the ONB group than in those in the IC group and the differences were significant.

• The financial burden related to bladder cancer treatment was significantly lower in the ONB group than in the IC group at 6, 12 and 18 months of follow-up (P = 0.05, P = 0.05 and P = 0.005, respectively)

CONCLUSIONS

• ONB is better than IC in terms of physical functioning, role functioning, social functioning, global health status/QoL and financial expenditure.

• ONB reconstruction provides better QoL outcomes than does IC urinary diversion.

 

Editorial: Life is good with orthotopic bladder substitutes!

In the present issue of the BJUI, Singh et al. [1] present the results of a non-randomized prospective study comprising 80 patients who underwent ileal conduit diversion and 84 who underwent orthotopic bladder substitution. Quality of life was assessed using the European Organisation for the Research and Treatment of Cancer quality-of-life questionnaire, the QLQ-30C, at 6, 12 and 18 months postoperatively. Physical and social functioning and global health status were significantly better in patients with orthotopic bladder substitution than in those who underwent ileal conduit diversion. Moreover, the postoperative financial burden was significantly lower for patients in the orthotopic bladder group than for those in the ileal conduit group, who required stoma appliances, a finding of particular importance not only in India, where the study was performed, but worldwide. The authors’ results are particularly impressive given their use of a questionnaire that included many items (‘Were you short of breath?’, ‘Did you need to rest?’, ‘Have you lacked appetite?’, ‘Have you been constipated?’, ‘Did you feel tense?’, ‘Did you worry’ or ‘Did you feel irritable?’, etc.) that can hardly discriminate between the quality of life of patients who underwent orthotopic bladder substitution and those who underwent ileal conduit diversion. To find significant differences between the two types of urinary diversion, despite such dilution factors, speaks strongly in favour of orthotopic bladder substitution.

The results of this prospective single-centre trial are of particular importance because, as the authors state, other investigators could not show such differences, presumably for a variety of reasons, such as too few patients or single follow-up assessments given at time points that varied from patient to patient. Quality-of-life assessment at similar follow-up time points, as performed by these authors, is important because, with adequate counselling, the postoperative function of orthotopic bladder substitutes improves over time.

Without a doubt, however, a poorly functioning orthotopic bladder substitute may lead to a poorer quality of life than a well-functioning ileal conduit diversion. Poor functional results and life-threatening complications can be largely avoided with ileal orthotopic bladder substitutes, provided the treating urologist has adequate knowledge of the procedure and the patient receives adequate postoperative education [2]. The major ways to ensure good results are:

  • appropriate patient selection (good renal function, regular follow-up possible);
  • the avoidance of damage to the sphincter apparatus and its innervation (individualized nerve-sparing cystectomy, minimum use of bipolar electrocautery near the pelvic plexus and membranous urethra);
  • the use of ileum instead of colon (better compliance) [3-5];
  • the avoidance of a funnel-shaped outlet that can result in kinking, outlet obstruction, residual infected urine and, in the worst case, lifelong need for clean intermittent catheterization (CIC) (Fig. 1).

By contrast to most other urological procedures, orthotopic bladder substitution requires proactive postoperative management [6] to ensure:

  • residual urine-free spontaneous voiding after catheter removal;
  • sterile urine to improve urinary continence and to reduce mucous production [7];
  • the prevention of salt loss syndrome and metabolic acidosis by increased salt intake and sodium bicarbonate substitution in the early postoperative period to ensure a base excess of +2;
  • a systematic increase in functional capacity by progressively expanding voiding intervals to obtain a reservoir capacity of ∼500 mL and, thus, a low end-fill pressure which ensures urinary continence day and night (the latter combined with the use of an alarm clock).

It is equally important to perform lifelong follow-up of patients and regularly at 6- to 12-month intervals so as to diagnose and treat early secondary complications, such as uretero-intestinal strictures or residual, infected urine. If the latter occurs, any form of outlet obstruction, such as ileal mucosa protruding in front of the bladder outlet, strictures or growth of inadvertently left prostatic tissue, must be looked for and treated. In our own experience, secondary outlet obstruction occurred in ∼20% of patients observed for 10 years. This rather high incidence is typical for intestinal bladder substitutes because when voiding, unlike the genuine bladder, there is no coordinated contraction of the reservoir wall which would result in an elevated voiding pressure which, in turn, would overcome an outlet resistance. Bladder substitutes empty mainly by gravitational force alone. If voiding is only possible by abdominal straining, then something must be wrong; therefore, instead of recommending CIC for patients who build up residual and consecutively infected urine, we strongly favour treating the outlet obstruction, usually on an outpatient basis. The avoidance of the need for CIC through surgical technique (no funnel-shaped outlet) and during regular follow-up by treating any potential cause of residual urine can substantially improve the patient’s quality of life. It also avoids the cost of catheters and the risk of infectious complications. Thanks to this active management and removal of any outlet obstruction, 96% of our patients followed for 10 years were still able to void spontaneously [8].

Urs E. Studer
Department of Urology, University Hospital Bern, Bern, Switzerland

References

  1. Singh V, Yadav R, Sinha RJ, Gupta DK. Prospective comparison of quality-of-life outcomes between ileal conduit urinary diversion and orthotopic neobladder reconstruction after radical cystectomy: a statistical model. BJU Int 2014; 113: 726–732
  2. Thurairaja R, Burkhard FC, Studer UE. The orthotopic neobladder. BJU Int 2008; 102: 1307–1313
  3. Berglund B, Kock NG, Myrvold HE. Volume capacity and pressure characteristics of the continent cecal reservoir. Surg Gynecol Obstet 1986; 163: 42–48
  4. Schrier BP, Laguna MP, van der Pal F, Isorna S, Witjes JA. Comparison of orthotopic sigmoid and ileal neobladders: continence and urodynamic parameters. Eur Urol 2005; 47: 679–685
  5. Varol C, Studer UE. Managing patients after an ileal orthotopic bladder substitution. BJU Int 2004; 93: 266–270
  6. Zehnder P, Dhar N, Thurairaja R, Ochsner K, Studer UE. Effect of urinary tract infection on reservoir function in patients with ileal bladder substitute. J Urol 2009; 181: 2545–2549
  7. Thurairaja R, Studer UE. How to avoid clean intermittent catheterization in men with ileal bladder substitution. J Urol 2008; 180: 2504–2509

 

Video: Orthotopic neobladder reconstruction by sigmoid colon

Prospective comparison of quality-of-life outcomes between ileal conduit urinary diversion and orthotopic neobladder reconstruction after radical cystectomy: a statistical model

Vishwajeet Singh, Rahul Yadav, Rahul Janak Sinha and Dheeraj Kumar Gupta
Department of Urology, King George Medical University, Lucknow, Uttar Pradesh, India

 

OBJECTIVE

• To conduct a prospective comparison of quality-of-life (QoL) outcomes in patients who underwent ileal conduit (IC) urinary diversion with those who underwent orthotopic neobladder (ONB) reconstruction after radical cystectomy for invasive bladder cancers.

PATIENTS AND METHODS

• Between January 2007 and December 2012, 227 patients underwent radical cystectomy and either IC urinary diversion or ONB (sigmoid or ileal) reconstruction.

• Contraindications for ON were impaired renal function (serum creatinine >2 mg/dL), chronic inflammatory bowel disease, previous bowel resection and tumour involvement at the bladder neck/prostatic urethra. Patients who did not have these contraindications chose to undergo either IC or ONB reconstruction, after impartial counselling.

• Baseline characteristics, including demographic profile, body mass index, comorbidities, histopathology of the cystoprostatectomy (with lymph nodes) specimen, pathological tumour stage, postoperative complications, adjuvant therapy and relapse, were recorded and compared.

• The European Organization for Research and Treatment of Cancer QoL questionnaire C30 version 3 was used to analyse QoL before surgery and 6, 12 and 18 months after surgery.

RESULTS

• Of the 227 patients, 28 patients in the IC group and 35 in the ONB group were excluded. The final analysis included 80 patients in the IC and 84 in the ONB group.

• None of the baseline characteristics were significantly different between the groups, except for age, but none of the baseline QoL variables were found to be correlated with age.

• In the preoperative phase, there were no significant differences in any of the QoL domains between the IC or the ONB groups. At 6, 12 and 18 months in the postoperative period, physical functioning (P < 0.001, P < 0.001 and P = 0.001, respectively), role functioning (P = 0.01, P = 0.01 and P = 0.003, respectively), social functioning (P = 0.01, P = 0.01 and P = 0.01, respectively) and global health status/QoL (P < 0.001, P < 0.001 and P = 0.002, respectively) were better in patients in the ONB group than in those in the IC group and the differences were significant.

• The financial burden related to bladder cancer treatment was significantly lower in the ONB group than in the IC group at 6, 12 and 18 months of follow-up (P = 0.05, P = 0.05 and P = 0.005, respectively)

CONCLUSIONS

• ONB is better than IC in terms of physical functioning, role functioning, social functioning, global health status/QoL and financial expenditure.

• ONB reconstruction provides better QoL outcomes than does IC urinary diversion.

 

Video: Peri-operative blood transfusion: outcomes in patients with bladder cancer

Impact of peri-operative blood transfusion on the outcomes of patients undergoing radical cystectomy for urothelial carcinoma of the bladder

Luis A. Kluth1,3, Evanguelos Xylinas1,4, Malte Rieken1,5, Maya El Ghouayel1, Maxine Sun1, Pierre I. Karakiewicz6, Yair Lotan7, Felix K.-H. Chun3, Stephen A. Boorjian8, Richard K. Lee1, Alberto Briganti9, Morgan Rouprêt10, Margit Fisch3, Douglas S. Scherr1 and Shahrokh F. Shariat1,2,11

1Department of Urology and 2Division of Medical Oncology, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY, USA, 3Department of Urology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany, 4Department of Urology, Cochin Hospital, Assistance Publique-Hopitaux de Paris, Paris Descartes University, Paris, France, 5Department of Urology, University Hospital of Basel, Basel, Switzerland, 6Department of Urology, University of Montreal, Montreal, QC, Canada, 7Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA, 8Department of Urology, Mayo Medical School and Mayo Clinic, Rochester, MN, USA, 9Department of Urology, Vita-Salute University, Milan, Italy, 10Department of Urology of la Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris, University Paris VI, Faculté de Médicine Pierre et Marie Curie, Paris, France, and 11Department of Urology, Medical University of Vienna, Vienna, Austria

L.A.K. and E.X. contributed equally to this work

Read the full article
OBJECTIVE

• To determine the association between peri-operative blood transfusion (PBT) and oncological outcomes in a large multi-institutional cohort of patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB).

PATIENTS AND METHODS

• We conducted a retrospective analysis of 2895 patients treated with RC for UCB.

• Univariable and multivariable Cox regression models were used to analyse the effect of PBT administration on disease recurrence, cancer-specific mortality, and any-cause mortality.

RESULTS

• Patients’ median (interquartile range [IQR]) age was 67 (60, 73) years and the median (IQR) follow-up was 36.1 (15, 84) months.

• Patients who received PBT were more likely to have advanced disease (P < 0.001), high grade tumours (P = 0.047) and nodal metastasis (P = 0.004).

• PBT was associated with a higher risk of disease recurrence (P = 0.003), cancer-specific mortality (P = 0.017), and any-cause mortality (P = 0.010) in univariable, but not multivariable, analyses (P > 0.05).

• In multivariable analyses, pathological tumour stage, pathological nodal stage, soft tissue surgical margin, lymphovascular invasion and administration of adjuvant chemotherapy were independent predictors of disease recurrence, cancer-specific mortality and any-cause mortality (all P values <0.002).

CONCLUSIONS

• Patients with UCB who underwent RC and received PBT had a greater risk of disease recurrence, cancer-specific mortality and any-cause mortality in univariable, but not multivariable, analysis.

• Although the greater need for PBT with more advanced disease is probably caused by a number of factors, including surgical and cancer-related factors, the present analysis showed that the disease characteristics rather than need for PBT led to worse outcomes.

 

Editorial: Diabetes mellitus and non-muscle-invasive bladder cancer: not just a coincidence?

Urologists are familiar with the plethora of comorbidities affecting patients with bladder cancer. Many are smoking-related, such as respiratory disease, ischaemic heart disease and peripheral vascular disease. Other conditions are associated with an ageing, increasingly obese population. Rieken et al. [1], present intriguing observations suggesting an association between diabetes mellitus (DM), its treatment and the prognosis of non-muscle-invasive bladder cancer (NMIBC). In a retrospective, multicentre cohort study of 1117 patients diagnosed with NMIBC, the authors conclude that patients taking metformin have better recurrence-free survival compared with patients with diabetes who did not take metformin. The Kaplan–Meier curves even hint at improved outcomes for patients taking metformin compared with the population without diabetes, although the difference did not reach statistical significance. Only 125 patients (out of 1117) had DM, of whom 43 were prescribed metformin. Outcome measures were recurrence and progression, with comparison of cancer-specific mortality not possible because of the low frequency of events. The study population was treated between 1996 and 2007, so re-resection was not routine, and rates of postoperative intravesical chemotherapy and adjuvant chemotherapy/immunotherapy were low. Treatment for some patients was therefore suboptimal by current standards, and there may have been differences between the multinational institutions.

The association between type 2 diabetes and the incidence of several cancer types (e.g. breast, colorectal and pancreatic) is well documented. The biological mechanisms responsible are unclear [2], and a causal relationship is debated. Postulated mechanisms include the effects of hyperinsulinaemia, hyperglycaemia and signalling pathways involving the IGF receptors. The protective effect of metformin is similarly unclear, although the authors cite studies indicating anti-proliferative properties.

A number of large cohort studies have endeavoured to show there is a higher risk of cancers in populations with diabetes. The challenge for such studies is the relatively low incident rate of bladder cancer in the population (17.1 per 100 000) [3]. Additionally, studies using general practice databases encounter problems obtaining data relating to bladder cancer characteristics. The increased detection of bladder cancer in the population with diabetes is a potential confounder, as monitoring using urine analysis is more likely.

Rieken et al. [1], in taking the opposite approach by identifying their cohorts on the basis of confirmed diagnosis of NMIBC, present accurate data regarding cancer characteristics but accept there is a potential for lack of accuracy in the recording of DM and treatment using chart review. We are not able to draw any conclusions regarding the severity of DM, its complications or compliance with prescribed medication. Future studies would be strengthened by incorporating tests such as HbA1c concentration as a marker for glycaemic control. Additionally, they do not specify the type of diabetes, although the reader can speculate that patients treated with metformin had type 2 DM. It is important to recognize that the pattern of cancer risk appears to be different for type 1 diabetes [4].

Whilst detailed discussion of the management of DM is outside the remit of a urological study, there are some important factors to be considered. Metformin is frequently recommended as a first-line agent in the management of type 2 DM [5]. It follows, therefore, that patients treated with metformin may be different from those requiring second- or third-line drugs and drug combinations; thus the cohort treated with metformin may be younger, exhibit better glycaemic control, and have improved renal function compared with those treated with other drugs and exogenous insulin. An important consideration is that rather than a protective effect being exerted by metformin, it may be that other hypoglycaemic agents have an adverse effect on NMIBC outcomes. Pioglitazone has recently been associated with an increased incidence of urothelial cancer when taken for >2 years, although effects on prognosis are not established [6]. Were the patients with diabetes not taking metformin in fact treated with hypoglycaemic agents implicated in the aetiology of bladder cancer? When considering the plausibility of biological mechanisms, the time-lag between exposure to carcinogen and the development of bladder cancer is pertinent. There is a prolonged time-lag between exposure to cigarette smoking and the development of bladder cancer, so are we ready to accept that drug exposure for a short time-scale is protective or causative? Finally, we must consider the clinical relevance of these findings. As metformin is the current first-line therapy, it may be contraindicated in those not prescribed it and conversion may not be possible.

Notwithstanding the above caveats, when treating patients with NMIBC we are often embarking on a lifelong process of treatment and surveillance. We are obliged as doctors to consider the implications of common comorbidities in order to tailor treatment. In much the same way that we now consider metabolic syndrome when evaluating erectile dysfunction, in the future we may need to consider NMIBC and DM together, and work collaboratively with other healthcare professionals to optimize the management of both conditions.

Joanne Cresswell
Department of Urology, James Cook University Hospital, Middlesbrough, UK

Read the full article

References

  1. Rieken M, Xylinas E, Kluth L et al. Association of diabetes mellitus and metformin use with oncological outcomes of patients with non-muscle-invasive bladder cancer. BJU Int 2013; 112: 1105–1112
  2. Johnson JA, Carstensen B, Witte D et al. Diabetes and cancer (1). Evaluating the temporal relationship between type 2 diabetes and cancer incidence. Diabetologica 2012; 55: 1607–1618
  3. Cancer Research UK. Bladder cancer, average number of new cases per year and age-specific incidence rates, 2006–2008. Cancer Research UK, 2012
  4. Zendehdel K, Nyren O, Ostenson CG, Adami HO, Ekbom A, Ye W. Cancer incidence in patients with type 1 diabetes mellitus: a population-based cohort study in Sweden. J Natl Cancer Inst 2003; 95: 1797–1800
  5. NICE. NICE Clinical Guideline, 66, 2008
  6. Azoulay L, Yin H, Filion K et al. The use of pioglitazone and the risk of bladder cancer in people with type 2 diabetes: nested case-control study. BMJ 2012; 344: e3645

Editorial: Is FDG-PET/CT ready for prime time?

Fluorodeoxyglucose positron-emission tomography (FDG PET)/computed tomography (CT) in bladder cancer

In this month’s issue Mertens et al. [1] present a retrospective analysis of the clinical impact of fluorodeoxyglucose positron-emission tomography (FDG PET)/CT in 96 patients with muscle-invasive bladder cancer. Muscle invasion is present in ≈30% of patients presenting with bladder cancer and is associated with a higher incidence of nodal and metastatic disease than non-muscle-invasive tumours [2]. Accurate staging in this patient group will influence management decisions to proceed to local therapies, to instigate neoadjuvant treatment before local therapy, or to offer palliative chemotherapy where there is imaging evidence and subsequent confirmation of metastatic disease [2].

While there have been a few previous studies investigating FDG PET or FDG PET/CT for staging bladder cancer [3-7], with reported sensitivities and specificities ranging from 60 to 81% and 67 to 94% respectively, to date there are few data describing the impact on clinical management. A recent FDG PET/CT study of 57 patients with bladder cancer [3] reported that management was changed in 68% of cases after PET suggesting that FDG PET/CT has a substantial impact on the management of these patients. However, most patients in that study underwent FDG PET/CT for a suspected recurrence (72%) and the remainder for initial staging (21%) or post-treatment monitoring (chemotherapy or radiotherapy; 7%); 44% of patients had metastatic disease.

In the study reported by Mertens et al. [1], clinical data obtained in 96 patients during the patients’ clinical pathway were reviewed retrospectively. FDG PET/CT staging with standard contrast-enhanced CT was discordant in 22% of cases (21 patients), where PET/CT predominantly upstaged patients, consistent with the previous reports [3, 4]. After PET/CT, the treatment recommendations changed in 13.5% (13 patients) due to disease upstaging. In seven of the 13 patients treatment recommendations altered from local to palliative, due to the presence of metastatic disease, and in the remaining six of the 13 patients, neoadjuvant treatment was recommended in addition to planned local therapy. In another four patients management changed as a consequence of detecting other incidental primary tumours with FDG PET/CT.

However, the final clinical impact of FDG PET/CT may be less. When actual treatment changes were recorded, in only eight of these 13 patients were the recommendations implemented, due to patient co-morbidity or patient wishes in the remainder, e.g. FDG PET/CT changed actual treatment in only 8% in this study (eight of 96 patients). Including the four patients in whom incidental other primary tumours were discovered, the management impact of FDG PET/CT was 12.5%.

There is no doubt that from current published data and supported by this study by Mertens et al. [1] that FDG PET/CT improves staging in bladder cancer due to its higher sensitivity for metastatic disease. However, the actual change in management is relatively low and more prospective data will be required to confirm its clinical and cost effectiveness in terms of outcome, both in a single and multicentre setting.

Vicky Goh* and Gary Cook*
*Division of Imaging Sciences and Biomedical Engineering, King’s College London, Department of Radiology, and Clinical PET Imaging Centre, Guy’s and St Thomas’ Hospitals NHS Foundation Trust, London, UK

Read the full article

References

  1. Mertens L, Fioole-Bruining A, Vegt E, Vogel W, van Rhijn B, Horenblas S. Impact of 18F-fluorodeoxyglucose (FDG)-positron-emission tomography/computed tomography (PET/CT) on management of patients with carcinoma invading bladder muscle. BJU Int 2013; 112: 729–734
  2. Kaufman DS, Shipley WU, Feldman AS. Bladder cancer. Lancet 2009; 374: 239–249
  3. Apolo AB, Riches J, Schoder H et al. Clinical value of fluorine-18 2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography in bladder cancer. J Clin Oncol 2010; 28: 3973–3978
  4. Kibel AS, Dehdashti F, Katz MD et al. Prospective study of [18F] Fluorodeoxyglucose positron emission tomography/computed tomography for staging of muscle-invasive bladder carcinoma. J Clin Oncol 2009; 27: 4314–4320
  5. Anjos DA, Etchebehere EC, Ramos CD, Santos AO, Albertotti C, Camargo EE. 18F-FDG PET/CT delayed images after diuretic for restaging invasive bladder cancer. J Nucl Med 2007; 48: 764–770
  6. Drieskens O, Oyen R, Van Poppel H, Vankan Y, Flamen P, Mortelmans L. FDG-PET for preoperative staging of bladder cancer. Eur J Nucl Med Mol Imaging 2005; 32: 1412–1417
  7. Kosuda S, Kison PV, Greenough R, Grossman HB, Wahl RL. Preliminary assessment of fluorine-18 fluorodeoxyglucose positron emission tomography in patients with bladder cancer. Eur J Nucl Med 1997; 24: 615–620

Video: Upstage, downstage: the spotlight on FDG-PET/CT for managing bladder cancer

Impact of 18F-fluorodeoxyglucose (FDG)-positron-emission tomography/computed tomography (PET/CT) on management of patients with carcinoma invading bladder muscle

Laura S. Mertens, Annemarie Fioole-Bruining*, Erik Vegt, Wouter V. Vogel, Bas W. van Rhijn and Simon Horenblas

Departments of Urology, *Radiology and Nuclear Medicine, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands

Read the full article
OBJECTIVE

• To evaluate the clinical impact of 18F-fluorodeoxyglucose (FDG)-positron-emission tomography/computed tomography (PET/CT) scanning, compared with conventional staging with contrast-enhanced CT imaging (CECT).

PATIENTS AND METHODS

• The FDG-PET/CT results of 96 consecutive patients with bladder cancer were analysed. Patients included in this study underwent standard CECT imaging of the chest and abdomen/pelvis <4 weeks before FDG-PET/CT.

• Based on the original imaging reports and recorded tumour stage before and after FDG-PET/CT imaging, the preferred treatment strategies before FDG-PET/CT and after FDG-PET/CT were determined for each patient using an institutional multidisciplinary guideline. One of the following treatment strategies was chosen: (i) local curative treatment; (ii) neoadjuvant/induction chemotherapy; or (iii) palliation.

• The changes in management decisions before and after FDG-PET/CT were assessed.

RESULTS

• The median (range) interval between CECT and FDG-PET/CT was 0 (029) days.

• In 21.9% of the patients, stage on FDG-PET/CT and CECT were different. Upstaging by FDG-PET/CT was more frequent than downstaging (19.8 vs 2.1%).

• Clinical management changed for 13.5% of patients as a result of FDG-PET/CT upstaging. In eight patients, FDG-PET/CT detected second primary tumours. This led to changes of bladder cancer treatment in another four of 96 patients (4.2%).

• All the management changes were validated by tissue confirmation of the additional lesions.

CONCLUSIONS

• FDG-PET/CT provides important additional staging information, which influences the treatment of carcinoma invading bladder muscle in almost 20% of cases.

• Patient selection for neoadjuvant/induction chemotherapy was improved and futile attempts at curative treatment in patients found to have metastases were avoided.

Bladder Cancer: a stagnant foe?

This month’s topic for the Twitter-based International Urology Journal Club #urojc was bladder cancer, with a paper titled Unaltered oncological outcomes of radical cystectomy with extended lymphadenectomy over three decades’ by Zehnder et al, published online in July 2013. Open access to the paper was kindly provided by the BJUI.

 Zehnder and colleagues undertook a retrospective analysis of the University of Southern California cohort and identified 1488 patients with muscle invasive bladder cancer who underwent radical cystectomy and extended pelvic lymph node dissection between 1998 and 2005. They also included 190 patients from the University of Bern cohort to determine outcomes in patients with clinical N0 disease who were upstaged on pathology to node positive disease. Analysis, performed based on decade of intervention, showed no significant difference in overall survival (OS) or recurrence free survival (RFS) over the three decades. 10-year RFS was 78-80% for organ confined, lymph node negative, 53-60% in locally advanced, LN –ve and 30% in LN positive patients.

 

 

Firstly, it has certainly been suggested that the overall survival and cancer free survival outcomes are not as good in broader population based studies (Ontario Cancer Registry). Why?

 

 

 

 

Analysis of the SEER database has shown that cancer specific survival and overall mortality has not improved for any clinical stage of bladder cancer and in fact suggests that the incidence is increasing in the United States.

 

 

And of course, we must always look at the study design and determine whether the outcomes are reflective of the patient populations that we see in practice.

 


 

The roles of neo- and adjuvant chemotherapy were discussed at length. Only 6% of patients received neoadjuvant chemotherapy, with worse OS and RFS in multivariate analysis. The use of adjuvant chemotherapy actually almost doubled from the 80’s to 90’s, stable in the 00’s at 29%.

 

  

 

 

 

 

 

If neoadjuvant chemotherapy is so widely recommended, why has its use failed to take off?

 

 

 

 

 

 

 

Jim Catto suggested an excellent clinical pathway for the implementation of neoadjuvant chemotherapy.

If indeed bladder cancer is the poor cousin of prostate cancer, why has progress stagnated and what can we change?

 

 

 

 

 

 

 

 

 

 

So what are my humble take home messages from the discussion surrounding this month’s #urojc paper?

  1. Current data suggests that we have made no significant progress in bladder cancer outcomes over the past 30 years
  2. Early referral and diagnosis coupled with timely intervention key; be wary of progression in context of high grade NMIBC
  3. Both surgeon volume and hospital volume are thought to be independent predictors of overall survival. Patie nts do best at a high volume facility under the care of a high-volume Uro-oncologist in a multidisciplinary context
  4. Neoadjuvant chemotherapy, despite randomized controlled trial evidence in favour of its use, has poor uptake in a real world setting. Advances in dense dose regimens (MVAC and Phase III GC underway) with resultant improvement in progression free survival, lower toxicity profile and fewer dose delays make for an attractive partner to radical cystectomy and extended pelvic lymph node dissection.

To finish with the words of the self-proclaimed Urology King of Twitter, Dr Ben Davies:

 

 

 

Winner of the best tweet prize for July’s #urojc was Mike Leveridge from Queens University, Canada – he was certainly a little frustrated with the apparent lack of progress we have made. The July #urojc Best Tweet Prize was kindly supported by the Nature Journal “Prostate Cancer Prostatic Diseases” which is edited by Dr Stephen Freedland and will be a complimentary 12 month online access to the journal.

 

 

 

 

 

 

Do join us for the August #urojc which commences on Sunday 4th/Monday 5th depending on your time zone.

Dr Helen Nicholson is an Australian Urology Trainee, currently based at The Sydney Adventist Hospital, NSW. Tweeted initially under duress, now a voluntary convert @DrHLN

 

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Article of the Week: Better fit than fat when it comes to radical cystectomy for bladder cancer

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 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.

Obesity is associated with worse oncological outcomes in patients treated with radical cystectomy

Thomas F. Chromecki1,2*, Eugene K. Cha1*, Harun Fajkovic1,3, Michael Rink1,4, Behfar Ehdaie1, Robert S. Svatek5, Pierre I. Karakiewicz6, Yair Lotan7, Derya Tilki8, Patrick J. Bastian8, Siamak Daneshmand9,Wassim Kassouf10, Matthieu Durand1, Giacomo Novara11, Hans-Martin Fritsche12, Maximilian Burger12, Jonathan I. Izawa13, Antonin Brisuda14, Marek Babjuk14, Karl Pummer2 and Shahrokh F. Shariat1

1Weill Medical College of Cornell University, New York, NY, USA, 2Medical University Graz, Graz, Austria, 3Landeskrankenhaus St Poelten, St Poelten, Austria, 4University Medical Centre Hamburg-Eppendorf, Hamburg, Germany, 5University of Texas Health Science Center San Antonio, San Antonio, TX, USA, 6University of Montréal, Montréal, QC, Canada, 7University of Texas Southwestern Medical Center, Dallas, TX, USA, 8Ludwig-Maximilians-University Munich, Klinikum Grosshadern, Munich, Germany, 9University of Southern California Keck School of Medicine and Norris Comprehensive Cancer Center, Los Angeles, CA, USA, 10McGill University Health Centre, Montréal, QC, Canada, 11University of Padua, Padua, Italy, 12Caritas St Josef Medical Centre, University of Regensburg, Regensburg, Germany, 13University of Western Ontario, London, ON, Canada, and 14Hospital Motol, 2nd Faculty of Medicine, Charles University, Praha, Czech Republic
*These authors contributed equally.

Read the full article
OBJECTIVE

• To investigate the association between body mass index (BMI) and oncological outcomes in patients after radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) in a large multi-institutional series.

PATIENTS AND METHODS

• Data were collected from 4118 patients treated with RC and pelvic lymphadenectomy for UCB. Patients receiving preoperative chemotherapy or radiotherapy were excluded.

• Univariable and multivariable models tested the effect of BMI on disease recurrence, cancer-specific mortality and overall mortality.

• BMI was analysed as a continuous and categorical variable (<25 vs 25–29 vs 30 kg/m2).

RESULTS

• Median BMI was 28.8 kg/m2 (interquartile range 7.9); 25.3% had a BMI <25 kg/m2, 32.5% had a BMI between 25 and 29.9 kg/m2, and 42.2% had a BMI 30 kg/m2.

• Patients with a higher BMI were older (P < 0.001), had higher tumour grade (P < 0.001), and were more likely to have positive soft tissue surgical margins (P = 0.006) compared with patients with lower BMI.

• In multivariable analyses that adjusted for the effects of standard clinicopathological features, BMI >30 was associated with higher risk of disease recurrence (hazard ratio (HR) 1.67, 95% confidence interval (CI) 1.46–1.91, P < 0.001), cancer-specific mortality (HR 1.43, 95% CI 1.24–1.66, P < 0.001), and overall mortality (HR 1.81, CI 1.60–2.05, P < 0.001). The main limitation is the retrospective design of the study.

CONCLUSIONS

• Obesity is associated with worse cancer-specific outcomes in patients treated with RC for UCB.

• Focusing on patient-modifiable factors such as BMI may have significant individual and public health implications in patients with invasive UCB.

 

Read Previous Articles of the Week

Editorial: Obesity is associated with worse oncological outcomes in patients treated with radical cystectomy

Michael R. Abern, Stephen J. Freedland and Brant A. Inman

Division of Urologic Surgery, Duke University Medical Center, Durham, NC, USA

Obesity is a worldwide epidemic: it is estimated over 300 million adults are obese and over 1 billion are overweight. As obesity is a risk factor for cancers and is modifiable, the authors of this report retrospectively analyse the association between body mass index (BMI) and outcomes in a large multinational cohort of bladder cancer patients that underwent radical cystectomy. They found that obese patients were older and more likely to have high-grade tumours. Furthermore, obese patients received inferior lymphadenectomies, had more positive margins, and were less likely to receive adjuvant chemotherapy. The end result is an association between obesity and bladder cancer recurrence, and both cancer-specific and overall mortality.

Although these data suggest that obesity is associated with poor radical cystectomy outcomes, this contrasts with evidence showing no link between obesity and bladder cancer mortality in population-based trials such as the Cancer Prevention Study II, which prospectively followed over 900 000 participants. Why the discrepancy? One possible explanation is the presence of confounding factors and one possible confounder is the presence of type 2 diabetes. In population-based studies that considered both BMI and diabetes, people with diabetes were noted to have an increased risk of developing bladder cancer independent of BMI, whereas the converse was not true. Additionally, diabetes has been associated with recurrence and progression of non-muscle invasive bladder cancer whereas obesity has not. The impact of diabetes was not adequately addressed in the current study.

Other limitations also probably affect the results. In the current study, overweight patients (BMI 25–30) had significantly better cancer-specific survival (hazard ratio 0.80, P = 0.01) than those of ‘normal’ weight (BMI < 25). However, a threshold BMI ≥ 30 has been shown to have poor sensitivity for obesity in elderly populations, with over 25% of patients with BMI under 30 qualifying as obese based on body fat. This may result in an overstatement of the effect of obesity. Conversely, the inclusion of underweight patients (BMI < 18.5) in the ‘normal’ group may underestimate the effect between obesity and outcome, as cachexia may be associated with poor outcomes. Another factor mentioned by the authors is the inferior lymphadenectomies performed in obese patients, which introduces a detection bias for lymph node positivity, the strongest predictor after advanced stage for all of their tested outcomes on multivariate analysis (hazard ratio 2.01–2.33, P < 0.001).

Although the true effect of obesity may be hard to quantify with these data, all would agree that maintaining a non-obese bodyweight will help many disease states with little apparent harm. Patients undergoing neoadjuvant chemotherapy before radical cystectomy have a 3-month window to lose weight and exercise more. This could improve surgical outcomes, and possibly tolerance of chemotherapy. Furthermore, if we can prove that obesity leads to increased bladder cancer recurrence or progression, a window of opportunity may exist when a low-risk tumour is diagnosed. Otherwise, we are left with the eighteenth century wisdom of Benjamin Franklin: ‘An ounce of prevention is worth a pound of cure.’

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