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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

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

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

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

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

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.

 

Read Previous Articles of the Week

 

Video: How do urology residents rate their laparoscopic experience?

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

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.

Article of the month: Seeing the light: HAL-PDD does not lead to lower recurrence rates of bladder tumours

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

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

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from T. O’Brien and K. Thomas summarising their paper.

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

Prospective randomized trial of hexylaminolevulinate photodynamic-assisted transurethral resection of bladder tumour (TURBT) plus single-shot intravesical mitomycin C vs conventional white-light TURBT plus mitomycin C in newly presenting non-muscle-invasive bladder cancer

Timothy O’Brien, Eleanor Ray, Kathryn Chatterton, Muhammad Shamim Khan, Ashish Chandra and Kay Thomas

Urology Centre, Guy’s and St Thomas’ NHS Foundation Trust, London, UK

OBJECTIVE

• To determine if photodynamic ‘blue-light’-assisted resection leads to lower recurrence rates in newly presenting non-muscle-invasive bladder cancer (NMIBC).

PATIENTS AND METHODS

• We conducted a prospective randomized trial of hexylaminolevulinate (HAL) photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumour (TURBT) plus single-shot intravesical mitomycin C vs standard white-light-assisted TURBT plus single-shot intravesical mitomycin C.

• A total of 249 patients with newly presenting suspected NMIBC enrolled at Guy’s Hospital between March 2005 and April 2010. Patients with a history of bladder cancer were excluded.

• The surgery was performed by specialist bladder cancer surgical teams.

• Of the eligible patients, 90% agreed to be randomized.

RESULTS

• Of the 249 patients, 209 (84%) had cancer and in 185 patients (89%) the cancer was diagnosed as NMIBC.

• There were no adverse events related to HAL in any of the patients randomized to the intravesical HAL-PDD arm.

• Single-shot intravesical mitomycin C was administered to 61/97 patients (63%) in the HAL-PDD arm compared with 68/88 patients (77%) in the white-light arm (P = 0.04)

• Intravesical HAL was an effective diagnostic tool for occult carcinoma in situ (CIS). Secondary CIS was identified in 25/97 patients (26%) in the HAL-PDD arm compared with 12/88 patients (14%) in the white-light arm (P = 0.04)

• There was no significant difference in recurrence between the two arms at 3 or 12 months: in the HAL-PDD and the white-light arms recurrence was found in 17/86 and 14/82 patients (20 vs 17%), respectively (P = 0.7) at 3 months, and in 10/63 and 15/67 patients (16 vs 22%), respectively (P = 0.4) at 12 months.

CONCLUSION

• Despite HAL-PDD offering a more accurate diagnostic assessment of a bladder tumour, in this trial we did not show that this led to lower recurrence rates of newly presenting NMIBC compared with the best current standard of care.

Read Previous Articles of the Week

 

Video: The two sides of blue light TURBT: better assessment but no lower recurrence rates

Prospective randomized trial of hexylaminolevulinate photodynamic-assisted transurethral resection of bladder tumour (TURBT) plus single-shot intravesical mitomycin C vs conventional white-light TURBT plus mitomycin C in newly presenting non-muscle-invasive bladder cancer

Timothy O’Brien, Eleanor Ray, Kathryn Chatterton, Muhammad Shamim Khan, Ashish Chandra and Kay Thomas

Urology Centre, Guy’s and St Thomas’ NHS Foundation Trust, London, UK

OBJECTIVE

• To determine if photodynamic ‘blue-light’-assisted resection leads to lower recurrence rates in newly presenting non-muscle-invasive bladder cancer (NMIBC).

PATIENTS AND METHODS

• We conducted a prospective randomized trial of hexylaminolevulinate (HAL) photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumour (TURBT) plus single-shot intravesical mitomycin C vs standard white-light-assisted TURBT plus single-shot intravesical mitomycin C.

• A total of 249 patients with newly presenting suspected NMIBC enrolled at Guy’s Hospital between March 2005 and April 2010. Patients with a history of bladder cancer were excluded.

• The surgery was performed by specialist bladder cancer surgical teams.

• Of the eligible patients, 90% agreed to be randomized.

RESULTS

• Of the 249 patients, 209 (84%) had cancer and in 185 patients (89%) the cancer was diagnosed as NMIBC.

• There were no adverse events related to HAL in any of the patients randomized to the intravesical HAL-PDD arm.

• Single-shot intravesical mitomycin C was administered to 61/97 patients (63%) in the HAL-PDD arm compared with 68/88 patients (77%) in the white-light arm (P = 0.04)

• Intravesical HAL was an effective diagnostic tool for occult carcinoma in situ (CIS). Secondary CIS was identified in 25/97 patients (26%) in the HAL-PDD arm compared with 12/88 patients (14%) in the white-light arm (P = 0.04)

• There was no significant difference in recurrence between the two arms at 3 or 12 months: in the HAL-PDD and the white-light arms recurrence was found in 17/86 and 14/82 patients (20 vs 17%), respectively (P = 0.7) at 3 months, and in 10/63 and 15/67 patients (16 vs 22%), respectively (P = 0.4) at 12 months.

CONCLUSION

• Despite HAL-PDD offering a more accurate diagnostic assessment of a bladder tumour, in this trial we did not show that this led to lower recurrence rates of newly presenting NMIBC compared with the best current standard of care.

Article of the week: What predicts cancer-specific survival after renal cancer recurrence?

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.

Time to recurrence is a significant predictor of cancer-specific survival after recurrence in patients with recurrent renal cell carcinoma – results from a comprehensive multi-centre database (CORONA/SATURN-Project)

Sabine D. Brookman-May1, Matthias May2, Shahrokh F. Shariat3, Giacomo Novara4, Richard Zigeuner5, Luca Cindolo6, Ottavio De Cobelli7, Cosimo De Nunzio8, Sascha Pahernik9, Manfred P. Wirth10, Nicola Longo11, Alchiede Simonato12, Sergio Serni13, Salvatore Siracusano14, Alessandro Volpe15, Giuseppe Morgia16, Roberto Bertini17, Orietta Dalpiaz5, Christian Stief1, and Vincenzo Ficarra4,18; Members of the CORONA-Project, the SATURN-Project, and the Young Academic Urologists Renal Cancer Group

1Department of Urology, Ludwig-Maximilians-University Munich, Campus Grosshadern, Munich, 2Department of Urology, St. Elisabeth Hospital Straubing, Straubing, Germany, 3Department of Urology and Division of Medical Oncology, Weill Cornell Medical College, New York, NY, USA, 4Department of Urology, University of Padua, Padua, Italy, 5Department of Urology, Medical University of Graz, Graz, Austria, 6Department of Urology, S. Pio Da Pietrelcina Hospital, Vasto, 7Department of Urology, European Institute of Oncology, Milan, 8Department of Urology, S. Andrea Hospital, Rome, Italy, 9Department of Urology, University of Heidelberg, Heidelberg, 10Department of Urology, Carl Gustav Carus Hospital, University of Dresden, Dresden, Germany, 11Department of Urology, University of Naples Federico II, Napoli, 12‘Luciano Giuliani’ Department of Urology, University of Genoa, Genoa, 13Department of Urology, University of Florence, Careggi Hospital, Florence, 14Department of Urology, University of Trieste, Trieste, 15Department of Urology, University of Eastern Piedmont, Maggiore della Carità Hospital, Novara, 16Departments of Urology, University of Catania, Catania, 17Department of Urology, Vita-Salute University San Raffaele, Milan, 18Department of Urology, Vita-Salute University San Raffaele, Milan, Italy, and OLV Robotic Surgery Institute, Aalst, Belgium

S.D.B.-M. and M.M contributed equally to this manuscript

OBJECTIVES

• To assess the prognostic impact of time to recurrence (TTR) on cancer-specific survival (CSS) after recurrence in patients with renal cell carcinoma (RCC) undergoing radical nephrectomy or nephron-sparing surgery.

• To analyse differences in clinical and histopathological criteria between patients with early and late recurrence.

PATIENTS AND METHODS

• Of 13 107 patients with RCC from an international multicentre database, 1712 patients developed recurrence in the follow-up (FU), at a median (interquartile range) of 50.1 (25–106) months.

• In all, 1402 patients had recurrence at ≤5 years (Group A) and 310 patients beyond this time (Group B).

• Differences in clinical and histopathological variables between patients with early and late recurrence were analysed.

• The influence of TTR and further variables on CSS after recurrence was assessed by Cox regression analysis.

RESULTS

• Male gender, advanced age, tumour diameter and stage, Fuhrman grade 3–4, lymphovascular invasion (LVI), and pN + stage were significantly more frequent in patients with early recurrence, who had a significantly reduced 3-year CSS of 30% compared with patients in Group B (41%; P = 0.001).

• Age, gender, tumour histology, pT stage, and continuous TTR (hazard ratio 0.99, P = 0.006; monthly interval) independently predicted CSS.

• By inclusion of dichotomised TTR in the multivariable model, a significant influence of this variable on CSS was present until 48 months after surgery, but not beyond this time.

CONCLUSIONS

• Advanced age, male gender, larger tumour diameters, LVI, Fuhrman grade 3–4, pN + stage, and advanced tumour stages are associated with early recurrence.

• Up to 4 years from surgery, a shorter TTR independently predicts a reduced CSS after recurrence.

 

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Editorial: Better late than early for long-term survival in patients with recurrence after renal carcinoma

In this paper, Brookman-May et al. [1] used a large multi-institutional database of over 13 000 patients from 23 centres in both Europe and the USA to examine the prognostic indicators of cancer-specific survival (CSS) in patients who had recurrence after primary surgery for RCC. Their analysis was based on a subset of 1712 patients who had recurrence during a median follow-up period of 50 months. All patients had undergone either radical nephrectomy or nephron-sparing surgery, with no evidence of metastasis at the time of surgery.

The authors have previously shown, in a related study based on a subset of 5000 patients from the same database, that lymphovascular invasion, Fuhrman grade 3–4, and pT stage > pT1 at the time of diagnosis were significantly associated with the development of late recurrence (defined as after >5 years) [2]. In this paper, the primary objective was to look at the effect of time to tumour recurrence (TTR) on CSS. In addition, clinical and histopathological comparisons were made between patients with early (<5 years) and late recurrence (>5 years).

Patients often want to know whether if they are recurrence-free after a period of time, their subsequent risk of dying from recurrence is reduced; this paper goes some way towards answering this question and showing that those with later recurrence had improved survival times. Specifically, the authors found that TTR was an independent predictor of CSS; i.e. if patients recurred early they had a worse CSS than those recurring late. This is similar to results from another group who reported that recurrent disease, particularly before 12 months, was associated with a poorer prognosis [3]. In the first 4 years of follow-up, a shorter TTR independently predicted lower CSS after recurrence [1]. When divided into those with early recurrence, Group A (N = 1402), and those with late recurrence, Group B (N = 310), patients in Group A were more likely to be male, of advanced age, have a greater tumour diameter and stage, have Fuhrman grade 3–4, with lymphovascular invasion and positive lymph node disease, than those in Group B. Patients in Group A had a 3-year CSS of 30% compared with those in Group B whose CSS was better at 41%. Age and gender were also independent predictors of CSS.

These results can help to guide the aftercare management of patients after primary surgery. Currently, primary surgery is the only recommended option for patients with localized RCC, although results from several phase III clinical trials looking at the role of adjuvant therapy, such as the SORCE, PROTECT and S-TRAC trials, are still awaited [4]. Furthermore, it is not known which group of patients are suitable for adjuvant chemotherapy, which is reflected in the subtly differing eligibility criteria for recruitment to the various trials [4]. The authors of the present study pointed out that a method of risk stratification may be useful to allow equal representation of early and late recurrence patients in treatment arms for clinical trials. Potentially, understanding the predictors of early recurrence may help to identify patients for whom adjuvant therapy may be beneficial.

Only 12% of patients with localized RCC in the present cohort developed recurrence after surgery [1]. This rate is lower than that found in the literature, where 20–30% recurrence rates of localized RCC have been reported [2, 5, 6]. Brookman-May et al. speculate that this lower rate is attributable to both an increase in early detection as well as improved surgical management in recent years. Furthermore, they acknowledge that the database is heterogeneous and that the study therefore has all the inherent limitations of a retrospective study.

The present paper clearly shows that the earlier the recurrence after surgery the lower the survival rate, but a clear strategy for the surveillance of localized RCC after primary surgery is currently lacking. Most follow-up protocols exercise a blanket ‘one for all’ policy with follow-up spaced at regular intervals to ensure patients who recur are detected early. Such a policy may not be intensive enough to detect early recurrence in some patients and may be excessive for the majority of patients where the risk of recurrence is low. Risk stratification of patients, by understanding the predictors of CSS after surgery, may help to tailor surveillance protocols to the individual and identify those for whom adjuvant therapy may be beneficial.

Kathie Wong and Ben Challacombe
The Urology Centre, Guy’s Hospital, Guy’s and St Thomas’ NHS Foundation Trust, London, UK

References

  1. Brookman-May S, May M, Shariat S et al. Time to recurrence is a significant predictor of cancer-specific survival after recurrence in patients with recurrent renal cell carcinoma – results from a comprehensive multi centre database (CORONA/SATURN Project). BJU Int 2013; 112: 909–916
  2. Brookman-May S, May M, Shariat SF et al. Features associated with recurrence beyond 5 years after nephrectomy and nephron-sparing surgery for renal cell carcinoma: development and internal validation of a risk model (PRELANE score) to predict late recurrence based on a large multicenter database (CORONA/SATURN Project). Eur Urol 2012; 64: 472–477
  3. Rodriguez-Covarrubias F, Gomez-Alvarado MO, Sotomayor M et al. Time to recurrence after nephrectomy as a predictor of cancer-specific survival in localized clear-cell renal cell carcinoma. Urol Int 2011; 86: 47–52
  4. Kim SP, Crispen PL, Thompson RH et al. Assessment of the pathologic inclusion criteria from contemporary adjuvant clinical trials for predicting disease progression after nephrectomy for renal cell carcinoma. Cancer 2012; 118: 4412–4420
  5. Hollingsworth JM, Miller DC, Daignault S, Hollenbeck BK. Five-year survival after surgical treatment for kidney cancer: a population-based competing risk analysis. Cancer 2007; 109: 1763–1768
  6. Breda A, Konijeti R, Lam JS. Patterns of recurrence and surveillance strategies for renal cell carcinoma following surgical resection. Expert Rev Anticancer Ther 2007; 7: 847–862

Article of the week: Going solo: using ultrasonography alone to guide PCNL

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

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

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from Dr Yan and colleagues of ultrasonography-guided percutaneous nephrolithotomy.

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

Percutaneous nephrolithotomy guided solely by ultrasonography: a 5-year study of >700 cases

Song Yan, Fei Xiang and Song Yongsheng

Division of Urology, Sheng Jing Hospital, China Medical University, Shenyang, China

OBJECTIVE

• To evaluate the safety and efficacy of percutaneous nephrolithotomy (PCNL) solely guided by ultrasonography (US).

PATIENTS AND METHODS

• From May 2007 to July 2012, 705 24-F-tract PCNL procedures were performed (679 patients, of whom 26 had bilateral stones).

• Calyceal puncture and dilatation were performed under US guidance in all cases.

• The procedure was evaluated for access success, length of postoperative hospital stay, complications (modified Clavien system), stone clearance and the need for auxiliary treatments.

RESULTS

• The mean (sd) operating time was 66 (25) min, with a mean (sd) postoperative hospital stay of 3.98 (1.34) days.

• The patients experienced a mean (sd) haemoglobin level decrease of 2.24 (2.02) g/day and the overall stone-free rate at 4 weeks after surgery was 92.6% in patients with a single calculus and 82.9% in patients with staghorn or multiple calculi.

• Auxiliary treatments, including shockwave lithotripsy in 52 patients, re-PCNL in 41 patients and ureteroscopy in 18 patients, were performed 1 week after the primary procedure in 111 (15.7%) cases for residual stones >4 mm in size.

• The sensitivities of intra-operative US-guidance and flexible nephroscopy for detecting significant residual stones and clinically insignificant residual fragments were 95.3 and 89.1%, respectively.

• There were 94 grade 1 (13.3%), 17 grade 2 (2.4%), and two grade 3 (0.3%) complications, but there were no grade 4 or 5 complications.

CONCLUSION

• Total US-guided PCNL is safe and convenient, and may be performed without any major complications and with the advantage of preventing radiation hazards and damage to adjacent organs.

 

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Editorial: Totally X-ray-free percutaneous nephrolithotomy: caveat emptor

In the accompanying paper, Yan et al. [1] present the outcomes of their study on percutaneous nephrolithotomy (PCNL) guided only by ultrasonography (US).

This is the largest series (705 patients) to date on PCNL purely under US control and reports stone-free and complication rates that are consistent with those commonly reported for PCNL guided by X-ray or by a combination of X-ray and US.

Since its introduction more than three decades ago, PCNL has traditionally been performed under fluoroscopic control by the majority of urologists, even though US guidance has now gained wide acceptance as a means of achieving renal access. Now, the most important international guidelines suggest that US be used in addition to fluoroscopy [2]. US guidance has the following advantages: it minimizes radiation exposure, allows the detection of viscera that can sometimes lie in the trajectory of the puncturing needle and avoids contrast-related complications. Furthermore, US provides imaging of the collecting system in three-dimensional orientations and helps to distinguish between anterior and posterior calyces with great accuracy. Nevertheless, the innovative concept proposed by Yan et al. [1], with their impressive series, concerns the whole procedure (puncture, creation of renal access and final look to rule out eventual residual fragments), and not only the safe accomplishment of the puncture solely under US guidance.

Caution should be taken in interpreting their results. This is a purely retrospective study which guarantees only a low level of evidence (3B). In addition, even though major complications arising during the creation of access were not reported in the paper, doubts remain about the safety of using only US guidance in monitoring the dilatation process by either balloon or coaxial dilators. The following questions still need to be addressed. How can the progression of dilators be monitored to avoid excessive inadvertent medial advances with the accompanying high risk of collecting system perforation? How can false passage of a working guidewire be detected early by US? What about obese patients in whom the effectiveness of US is generally impaired?

To balance the risks and benefits of guidance solely by US, a middle ground could be represented by US guidance aided by ureteroscopic monitoring of the dilatation process using the so-called ‘Endovision technique’ [3], as is possible during endoscopic combined intrarenal surgery (ECIRS) (Fig. 1). In view of the risks, it should be stressed that, even though PCNL guided solely by US is an attractive option, biplanar C-arm fluoroscopy should always be present in the operating room.

It is well known that radiation hazard is directly proportional to cumulative radiation exposure time, so US guidance provides an obvious advantage in terms of absence of radiation for patient and operating room staff, but is the extent of this advantage really known? It is important to underline that the amount of radiation exposure during PCNL is not particularly great, measuring on average 0.56 mSv for the patient and 0.28 mSv for the urologist [4]. By contrast, unenhanced CT involves a significant radiation exposure of 8.6 mSv [5], which is of course particularly relevant for patients with stones, who are often quite young and likely to experience recurrence. According to the ‘as low as reasonably achievable’ (or ALARA) principle, replacing CT scans with US in the follow-up would have a much greater impact on reducing radiation exposure in adult patients (in the present series patients undergo two CT scans after surgery, at 48 h and 4 weeks, and one preoperative CT scan!) than would renouncing the safety guaranteed by X-ray monitoring during endourology.

Finally, it is of paramount importance to stress that, in the current climate in which malpractice litigation related to endourology continues to rise [6], it is still advisable that PCNL guided solely by US should be performed only in trials for which approval of the local institutional review board has been obtained.

To conclude, Yan et al. [1] propose an alternative approach to PCNL that involves solely US guidance, but some doubts remain. Only further well designed, prospective, comparative and possibly randomized studies will allow us to draw definitive conclusions.

Guido Giusti
Head of Stone Center & European Training, Center in Endourology, Humanitas Clinical and Research Center, Milan, Italy

References

  1. Yan S, Xiang F, Yongsheng S. Percutaneous nephrolithotomy guided solely by ultrasonography: a 5-year study of >700 cases. BJU Int 2013; 112: 965–971
  2. Türk C, Knoll T, Petrik A et al. 2013 EAU Guidelines on Urolithiasis
  3. Scoffone CM, Cracco CM et al. Endoscopic Combined intrarenal surgery in galdakao-modified supine valdivia position: a new standard for percutaneous nephrolithotomy? Eur Urol 2008; 54: 1393–1403
  4. Kumari G, Kumar P, Wadhwa P, Aron M, Gupta NP, Dogra PN. Radiation exposure to the patient and operating room personnel during percutaneous nephrolithotomy. Int Urol Nephrol 2006; 38: 207–210
  5. Katz SI, Saluja S, Brink JA, SForman HP. Radiation dose associate with unenhanced CT for suspected renal colic: impact of repetitive studies. AJR Am J Roentgenol 2006; 186: 1120–1124
  6. Duty B, Okhunov Z, Okeke Z, Smith A. Medical malpractice in endourology: analysis of closed cases from the State of New York. J Urol 2012; 187: 528–532
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