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Editorial: Does performing LND at nephrectomy give a survival benefit or not?

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We read with interest the article by Sun et al. [1] in this issue of the BJU International. We were pleased to see another research group interested in this important aspect of the management of patients with lymph-node-positive non-metastatic RCC. The question of the benefits of lymphadenectomy in such patients could not be answered by the European Organization for Research and Treatment of Cancer randomized trial [2], as only 4% of clinically node-negative patients had micrometastatic disease.

Given some of the complexities involved in the analysis of Surveillance, Epidemiology and End Results data and the particular statistical analysis we used in showing a benefit to increasing nodal yield in patients with positive nodes [3], we were reassured that Sun et al. were able to validate our findings when replicating our data extraction and analysis. They performed two additional analyses and the four results are shown in Table 1.

 

While Sun et al. concluded that multiple imputation introduces bias into the findings, inspection of the estimates of the impact of lymph node dissection (the hazard ratio) appear identical. If bias is a deviation of an estimate from the truth [4], we would argue that Sun et al. found no evidence of bias introduced by the multiple imputation method. This is not to say that all four analyses are free from potential bias – the reported hazard ratios may in fact still be biased results – but that there is no more bias in the multiple imputation model than in the others. In addition, we were somewhat surprised to see the use of a missing indicator approach proposed as less likely than multiple imputation to introduce bias as studies have shown the opposite [5].

Furthermore, the CIs show that the benefit to extent of lymphadenectomy may be as great as a 34% reduction in cancer-related death, with exclusion of all but a 5% increase in death associated with the procedure. CIs provide extremely valuable information, particularly in the setting of marginally significant or nonsignificant P values. Sun et al. could have strengthened their paper on statistical considerations by discussing this further. In fact, we would argue that their additional analyses lend further support to the potential benefit of the extent of lymphadenectomy.

The most notable difference across the analyses is a drift in the P value. We would argue that this mirrors the loss in power associated with the censoring of almost 3000 patients (28%) with missing grades. In addition, grade does not appear to be missing at random, as patients with missing tumour grades were associated with larger tumours, higher local stage, increased probability of nodal involvement and increased risk of kidney cancer death. The censoring of such patients may in and of itself introduce bias, although again the hazard ratios do not seem to reflect this. The devaluation of the P value continues to be an active area of biostatistical research, although in general journals have not foregone its inclusion in favour of an entirely Bayesian approach [6]. We believe that, in this case, Sun et al. have taken a far too traditional approach to interpretation of small differences in P values, particularly in the setting of changing sample sizes.

We agree with Sun et al. that consideration of another randomized trial focused on patients at high risk of nodal involvement or with clinically apparent nodes on CT is warranted based upon our combined results.

Jared M. Whitson and Maxwell Meng
Department of Urology, Kaiser Permanente South Sacramento Medical Center, Sacramento, CA, USA

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References

  1. Sun M, Trinh Q-D, Bianchi M et al. Extent of lymphadenectomy does not improve survival of patients with renal cell carcinoma and nodal metastases: biases associated with handling of missing data. BJU Int 2014; 113: 36–42
  2. Blom JH, van Poppel H, Marechal JM et al. Radical nephrectomy with and without lymph-node dissection: final results of European Organization for Research and Treatment of Cancer (EORTC) randomized phase 3 trial 30881. Eur Urol 2009; 55: 28–34
  3. Whitson JM, Harris CR, Reese AC, Meng MV. Lymphadenectomy improves survival of patients with renal cell carcinoma and nodal metastases. J Urol 2011; 185: 1615–1620
  4. Grimes DA, Schulz KF. Bias and causal associations in observational research. Lancet 2002; 359: 248–252
  5. Greenland S, Finkle WD. A critical look at methods for handling missing covariates in epidemiologic regression analyses. Am J Epidemiol 1995; 142: 1255–1264
  6. Goodman SN. Toward evidence-based medical statistics. 2: the Bayes factor. Ann Intern Med 1999; 130: 1005–1013
 

Video: Survival for RCC and nodal metastases

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Extent of lymphadenectomy does not improve the survival of patients with renal cell carcinoma and nodal metastases: biases associated with the handling of missing data

Maxine Sun*, Quoc-Dien Trinh*‡, Marco Bianchi*, Jens Hansen*††, Firas Abdollah, Zhe Tian*, Shahrokh F. Shariat§, Francesco Montorsi, Paul Perrotte† and Pierre I. Karakiewicz*†

*Cancer Prognostics and Health Outcomes Unit, †Department of Urology, University of Montreal Health Center, Montreal, Canada, ‡Vattikuti Urology Institute, Henry Ford Health System, Detroit, MI, §Department of Urology,Weill Medical College of Cornell University, New York, NY, USA, Department of Urology, Vita-Salute San Raffaele University, Milan, Italy, and ††Martini Clinic, Prostate Cancer Center Hamburg-Eppendorf, Hamburg, Germany

Maxine Sun and Quoc-Dien Trinh contributed equally to this study.

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OBJECTIVE

• Previous studies showed no survival benefit with respect to performing lymph node dissection (LND) at nephrectomy, whereas a recent population-based analysis suggested otherwise, although the latter relied on imputation. To reconcile the findings of that study by critically evaluating the handling of missing data.

PATIENTS AND METHODS

• Study participants comprised patients diagnosed with non-metastatic renal cell carcinoma (RCC) of all stages who underwent LND at nephrectomy (n = 10 596).

• Multivariable Cox regression models were performed to predict cancer-specific mortality (CSM), where the primary variable of interest was the extent of LND.

• To examine differences in approaches with respect to handling missing data, separate analyses were performed: (i) imputed population; (ii) exclusion of patients with missing data; and (iii) inclusion of patients with missing data as a sub-category.

RESULTS

• Overall, 2916 (28%) patients had missing tumour grade.

• In multivariable analyses, our findings showed that increasing the extent of LND was associated with a significant protective effect on CSM in patients with pN1 after imputation (hazard ratio [HR], 0.82; P = 0.04).

• By contrast, the extent of LND was no longer significantly associated with a lower risk of CSM after excluding patients with a missing tumour grade (HR, 0.83; P = 0.1) or when including patients with missing tumour grade as a sub-category (HR, 0.82; P = 0.05).

CONCLUSIONS

• The findings of the present study failed to corroborate the association of a survival benefit with increasing extent of LND at nephrectomy.

• The different methodologies employed to account for missing data may introduce important biases.

• Such considerations are non-negligible with respect to the interpretation of results for investigators who rely on administrative cohorts.

Article of the Month: HIV no barrier to circumcision

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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.

This month our lead article on HIV and circumcision comes from Uganda. The front cover of January’s issue shows the Nile at Lake Victoria in Uganda. If you only have time to read one article this week, it should be this one in the real world there are only two types and cost of these HIV tests is different read below to understand the difference.

Male circumcision wound healing in human immunodeficiency virus (HIV)-negative and HIV-positive men in Rakai, Uganda

Godfrey Kigozi*, Richard Musoke*, Nehemiah Kighoma*, Stephen Watya*†, David Serwadda*‡, Fred Nalugoda*, Noah Kiwanuka‡, James Nkale*, Fred Wabwire-Mangen‡, Frederick Makumbi*‡, Nelson K. Sewankambo§, Ronald H. Gray* and Maria J. Wawer*

*Rakai Health Sciences Program, Entebbe, †Urocare, ‡School of Public Health, Makerere University, and §College of Health Sciences, Makerere University, Kampala, Uganda, and ¶Department of Epidemiology, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD, USA

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OBJECTIVE

• To assess completed wound healing after medical male circumcision (MMC) among human immunodeficiency virus (HIV)-negative and HIV-positive men with cluster of differentiation 4 (CD4) counts of <350 and ≥350 cells/mm3, as minimal data are available on the safety of MMC among HIV-positive men with low CD4 counts.

PATIENTS AND METHODS

• In all, 262 HIV-negative and 177 HIV-positive consenting males aged ≥12 years accepted MMC using the dorsal slit procedure and were enrolled in the study.

• Socio-demographic and behavioural data and blood for HIV testing and CD4 counts were collected at baseline.

• Participants were followed weekly to collect information on resumption of sex, condom use and both self-reported and clinically assessed wound healing.

• The proportions healed among HIV-positive men were compared with HIV-negative men. Time to complete wound healing was assessed by Kaplan–Meier survival analysis.

RESULTS

• There were no statistically significant differences in the proportion of men healed by HIV status.

• At 4 weeks, the proportions healed were 85.9% in HIV-negative men, 77.4% in HIV-positive men with a CD4 count of ≥350 cells/mm3and 87.1% in HIV-positive men with a CD4 count of <350 cells/mm3.

• The median time to healing was 4 weeks and did not vary by HIV or CD4 status.

• All men had certified complete wound healing at 6 weeks after MMC. In all, 1.4% of HIV-positive men with a CD4 count of <350 cells/mm3 resumed sex before healing, compared with 8.5% among HIV-positive men with a CD4 count of ≥350 cells/mm3 (P = 0.052) and 7.8% (P = 0.081) among HIV-negative men.

CONCLUSION

• Inclusion of HIV-positive men with low CD4 counts in MMC services is not deleterious to postoperative wound healing.

 

Read Previous Articles of the Week

 

Editorial: Circumcision – follow-up or not?

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There is an excellent study from Uganda in this issue of the BJUI [1]. It looks at the rate of healing of men undergoing prophylactic circumcision. Some had HIV; others not. What they termed ‘complete wound healing’ was an intact scar without a scab, sutures or a sinus – effectively a ‘sealed’ wound. There are several useful data therein:

  • all men had healed by 6 weeks; the median being 4 weeks.
  • HIV status did not appear to delay wound healing, even with low CD4 counts.
  • the patient was 95% likely to judge wound healing correctly himself.
  • routine circumcision can be safely carried out by trained medical officers.
  • a complication rate of 0.5% was reported.

So what follow-up, if any, is necessary after circumcision? Based on this population it would appear that a well instructed/consented patient can be relied on to judge healing after prophylactic circumcision. They probably do not need follow-up provided their expectations are managed well, and there is ease of access to return should problems arise.

However, this may not be generalizable to men having circumcision for phimosis or other abnormality of foreskin. These patients may have delayed healing, meatal issues or a urethral stricture upstream. Histopathological examination of abnormal foreskins is sensible also as further treatment/follow-up may indicated.

I recommend a read of this superb paper.

Paul K. Hegarty
Consultant Urological Surgeon, Mater Private, Cork, Ireland

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Article of the week: Getting to the core of the matter with PIRADS scoring

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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.

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

Histology core-specific evaluation of the European Society of Urogenital Radiology (ESUR) standardised scoring system of multiparametric magnetic resonance imaging (mpMRI) of the prostate

Timur H. Kuru*†, Matthias C. Roethke†, Philip Rieker*, Wilfried Roth‡, Michael Fenchel†, Markus Hohenfellner*, Heinz-Peter Schlemmer† and Boris A. Hadaschik*

*Department of Urology, University Hospital Heidelberg, †Department of Radiology, German Cancer Research Center (DKFZ), and ‡Institute of Pathology, University of Heidelberg, Heidelberg, Germany

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Link to Video: MRI-Navigated Stereotactic Prostate Biopsy

OBJECTIVES

• To evaluate the Prostate Imaging Reporting and Data System (PIRADS) in multiparametric magnetic resonance imaging (mpMRI) based on single cores and single-core histology.

• To calculate positive (PPV) and negative predictive values (NPV) of different modalities of mpMRI.

PATIENTS AND METHODS

• We performed MRI-targeted transrectal ultrasound-guided perineal prostate biopsies on 50 patients (mean age 66 years, mean PSA level of 9.9 ng/mL) with suspicion of prostate cancer. The biopsy trajectories of every core taken were documented in three dimensions (3D) in a 3D-prostate model.

• Every core was evaluated separately for prostate cancer and the performed biopsy trajectories were projected on mpMRI images.

• PIRADS scores of 1177 cores were then assessed by a histology ‘blinded’ uro-radiologist in T2-weighted (T2W), dynamic contrast-enhanced (DCE), diffusion-weighted imaging (DWI) and magnetic resonance spectroscopy (MRS).

RESULTS

• The PIRADS score was significantly higher in cores positive for cancer than in negative cores.

• There was a significant correlation between the PIRADS score and histopathology for every modality.

• Receiver operating characteristic (ROC) analysis showed excellent specificity for T2W (90% peripheral zone/97% transition zone) and DWI (98%/97%) images regardless of the prostate region observed. These numbers decreased for DCE (80%/93%) and MRS (76%/83%).

• All modalities had NPVs of 99%, if a PIRADS score threshold of 2 (for T2W, DCE, and MRS) or 3 (for DWI) was used. However, PPVs were low.

CONCLUSIONS

• Our results show that PIRADS scoring is feasible for clinical routine and allows standardised reporting.

• PIRADS can be used as a decision-support system for targeting of suspicious lesions.

• mpMRI has a high NPV for prostate cancer and, thus, might be a valuable tool in the initial diagnostic evaluation.

 

Read Previous Articles of the Week

 

Editorial: Too many men still undergo needless prostate biopsy

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Multiple studies have shown that only one in three or four men with a raised PSA level prove to have prostate cancer and many men suffer potentially life-threatening complications from transrectal prostate biopsy. There is an urgent need for better risk stratification of men with elevated PSA levels. Any such test should have a high negative predicative value (NPV; small number of significant cancers missed) but also a high positive predictive value (PPV; i.e. the yield would be high and there would be very few false positives) to diminish the number of unnecessary biopsies. Multiparametric MRI (mpMRI) of the prostate, especially with a stronger 3 T magnet, has been advocated for this purpose. The parameters refer to the separate MRI sequences used, typically at least three. Sequences can not only study the anatomy of the gland (standard T2-weighted MRI), but there is also a measure of the tissue cellularity (diffusion-weighted MRI), vascularity (dynamic contrast-enhanced MRI) or biochemistry (magnetic resonance spectroscopy). Initial data have shown promise but the changes seen on these various sequences can be subtle and interpretation is subjective. Naturally observer experience plays a large part but a standardised scoring system, the so called Prostate Imaging Reporting and Data System (PIRADS) system, has been proposed to improve reporting performance [1]. Each parameter is scored on a scale of 1–5 according to the likelihood of cancer. Scoring systems are always a compromise between the NPV and PPV, and so far there is no agreement where the threshold for each parameter should be set. In the original document, the authors proposed that a score of 4 or 5 signifies a high likelihood or almost certainty of cancer, whilst scores of 1 or 2 denote a high likelihood of benign tissue. A score of 3 is evens. The paper by Kuru et al. [2] shows a high NPV only when the threshold was set at the low level of 2 for each parameter. Predictably, at this threshold the PPV was extremely low, and therefore many men would still undergo unnecessary biopsy. Another similar paper advocated a mean threshold of 3, but even then the PPV was 38% with a NPV of 95% [3]. Both these papers are retrospective studies, in particular the MRI readings were done retrospectively. Nevertheless, the low PPV is disappointing. The results of prospective studies with multiple readers are keenly awaited and I hope that that these will find a higher PPV for mpMRI, and we can to move to an era when fewer men undergo needless prostate biopsy.

Uday Patel
St George’s Hospital, London, UK

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References

  1. Barentsz JO, Richenberg J, Clements R et al. ESUR prostate MR guidelines 2012. Eur Radiol 2012; 22: 746–757
  2. Kuru T, Roethke M, Rieker P et al. Histology core-specific evaluation of the European Society of Urogenital Radiology (ESUR) standardised scoring system of multiparametric magnetic resonance imaging (mpMRI) of the prostate. BJU Int 2013; 112:1080–1087
  3. Portalez D, Mozer P, Cornud F et al. Validation of the European Society of Urogenital Radiology scoring system for prostate cancer diagnosis on multiparametric magnetic resonance imaging in a cohort of repeat biopsy patients. Eur Urol 2012; 62: 986–996

Article of the week: What does metformin use have to do with NMIBC outcomes?

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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 of Dr. Rieken discussing his paper.

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

Association of diabetes mellitus and metformin use with oncological outcomes of patients with non-muscle-invasive bladder cancer

Malte Rieken1,3, Evanguelos Xylinas1,4, Luis Kluth1,5, Joseph J. Crivelli1, James Chrystal1, Talia Faison1, Yair Lotan6, Pierre I. Karakiewicz7, Harun Fajkovic10, Marek Babjuk8, Alexandra Kautzky-Willer10, Alexander Bachmann3, Douglas S. Scherr1 and Shahrokh F. Shariat1,2,10

1Department of Urology, 2Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY, USA, 3Department of Urology, University Hospital Basel, Basel, Switzerland, 4Department of Urology Cochin Hospital, APHP, Paris Descartes University, Paris, France, 5Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, 6Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA, 7Department of Urology, University of Montreal, Montreal, QC, Canada, 8Department of Urology, Hospital Motol, Second Faculty of Medicine, Charles University, Prague, Czech Republic, 9Unit of Gender Medicine, Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria, and 10Department of Urology, Medical University of Vienna, Vienna, Austria

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OBJECTIVE

• To assess the association between diabetes mellitus (DM) and metformin use with prognosis and outcomes of non-muscle-invasive bladder cancer (NMIBC)

PATIENTS AND METHODS

• We retrospectively evaluated 1117 patients with NMIBC treated at four institutions between 1996 and 2007.

• Cox regression models were used to analyse the association of DM and metformin use with disease recurrence, disease progression, cancer-specific mortality and any-cause mortality.

RESULTS

• Of the 1117 patients, 125 (11.1%) had DM and 43 (3.8%) used metformin.

• Within a median (interquartile range) follow-up of 64 (22–106) months, 469 (42.0%) patients experienced disease recurrence, 103 (9.2%) experienced disease progression, 50 (4.5%) died from bladder cancer and 249 (22.3%) died from other causes.

• In multivariable Cox regression analyses, patients with DM who did not take metformin had a greater risk of disease recurrence (hazard ratio [HR]: 1.45, 95% confidence interval [CI] 1.09–1.94, P = 0.01) and progression (HR: 2.38, 95% CI 1.40-4.06, P = 0.001) but not any-cause mortality than patients without DM.

• DM with metformin use was independently associated with a lower risk of disease recurrence (HR: 0.50, 95% CI 0.27–0.94, P = 0.03).

CONCLUSION

• Patients with DM and NMIBC who do not take metformin seem to be at an increased risk of disease recurrence and progression; metformin use seems to exert a protective effect with regard to disease recurrence.

• The mechanisms behind the impact of DM on patients with NMIBC and the potential protective effect of metformin need further elucidation.

 

Read Previous Articles of the Week

 

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

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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

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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

Video: Metformin for diabetics with NMIBC

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Association of diabetes mellitus and metformin use with oncological outcomes of patients with non-muscle-invasive bladder cancer

Malte Rieken1,3, Evanguelos Xylinas1,4, Luis Kluth1,5, Joseph J. Crivelli1, James Chrystal1, Talia Faison1, Yair Lotan6, Pierre I. Karakiewicz7, Harun Fajkovic10, Marek Babjuk8, Alexandra Kautzky-Willer10, Alexander Bachmann3, Douglas S. Scherr1 and Shahrokh F. Shariat1,2,10

1Department of Urology, 2Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY, USA, 3Department of Urology, University Hospital Basel, Basel, Switzerland, 4Department of Urology Cochin Hospital, APHP, Paris Descartes University, Paris, France, 5Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, 6Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA, 7Department of Urology, University of Montreal, Montreal, QC, Canada, 8Department of Urology, Hospital Motol, Second Faculty of Medicine, Charles University, Prague, Czech Republic, 9Unit of Gender Medicine, Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria, and 10Department of Urology, Medical University of Vienna, Vienna, Austria

Read the full article
OBJECTIVE

• To assess the association between diabetes mellitus (DM) and metformin use with prognosis and outcomes of non-muscle-invasive bladder cancer (NMIBC)

PATIENTS AND METHODS

• We retrospectively evaluated 1117 patients with NMIBC treated at four institutions between 1996 and 2007.

• Cox regression models were used to analyse the association of DM and metformin use with disease recurrence, disease progression, cancer-specific mortality and any-cause mortality.

RESULTS

• Of the 1117 patients, 125 (11.1%) had DM and 43 (3.8%) used metformin.

• Within a median (interquartile range) follow-up of 64 (22–106) months, 469 (42.0%) patients experienced disease recurrence, 103 (9.2%) experienced disease progression, 50 (4.5%) died from bladder cancer and 249 (22.3%) died from other causes.

• In multivariable Cox regression analyses, patients with DM who did not take metformin had a greater risk of disease recurrence (hazard ratio [HR]: 1.45, 95% confidence interval [CI] 1.09–1.94, P = 0.01) and progression (HR: 2.38, 95% CI 1.40-4.06, P = 0.001) but not any-cause mortality than patients without DM.

• DM with metformin use was independently associated with a lower risk of disease recurrence (HR: 0.50, 95% CI 0.27–0.94, P = 0.03).

CONCLUSION

• Patients with DM and NMIBC who do not take metformin seem to be at an increased risk of disease recurrence and progression; metformin use seems to exert a protective effect with regard to disease recurrence.

• The mechanisms behind the impact of DM on patients with NMIBC and the potential protective effect of metformin need further elucidation.

Article of the week: Behind the curve: residents’ access to RAL is poor in Europe

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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 of Dr. Furriel discussing his paper.

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

Training of European urology residents in laparoscopy: results of a pan-European survey

Frederico T.G. Furriel, Maria P. Laguna*, Arnaldo J.C. Figueiredo, Pedro T.C. Nunes and Jens J. Rassweiler†

Department of Urology and Renal Transplantation, University Hospital of Coimbra, Coimbra, Portugal, *Department of Urology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, and †Department of Urology, Klinikum Heilbronn, University of Heidelberg, Heilbronn, Germany

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OBJECTIVE

• To assess the participation of European urology residents in urological laparoscopy, their training patterns and facilities available in European Urology Departments.

MATERIALS AND METHODS

• A survey, consisting of 23 questions concerning laparoscopic training, was published online as well as distributed on paper, during the Annual European Association of Urology Congress in 2012.

• Exposure to laparoscopic procedures, acquired laparoscopic experience, training patterns, training facilities and motivation were evaluated.

• Data was analysed with descriptive statistics.

RESULTS

• In all, 219 European urology residents answered the survey.

• Conventional laparoscopy was available in 74% of the respondents’ departments, while robotic surgery was available in 17% of the departments.

• Of the respondents, 27% were first surgeons and 43% were assistants in conventional laparoscopic procedures. Only 23% of the residents rated their laparoscopic experience as at least ‘satisfactory’; 32% of the residents did not attend any course or fellowship on laparoscopy.

• Dry laboratory was the most frequent setting for training (33%), although 42% of the respondents did not have access to any type of laparoscopic laboratory.

• The motivation to perform laparoscopy was rated as ‘high’ or ‘very high’ by 77% of the respondents, and 81% considered a post-residency fellowship in laparoscopy.

CONCLUSIONS

• Urological laparoscopy is available in most European training institutions, with residents playing an active role in the procedure. However, most of them consider their laparoscopic experience to be poor.

• Moreover, the availability of training facilities and participation in laparoscopy courses and fellowships are low and should be encouraged.

 

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