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Highlights from BAUS 2016

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In the week following Britain’s exit from Europe after the BREXIT referendum, BAUS 2016 got underway in Liverpool’s BT convention Centre. This was the 72nd meeting of the British Association of Urological Surgeons and it was well attended with 1120 delegates (50% Consultant Member Urologists, 30% Trainees, 10% Non member Urologists/Other, 10% Nurses, HCP’S, Scientists).

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Monday saw a cautionary session on medicolegal aspects in Andrology, focusing on lawsuits over the last year. Mr Mark Speakman presented on the management issue of testicular torsion. This sparked further discussion on emergency cover for paediatrics with particular uncertainty noted at 4 and 5 year olds and great variation in approach dependent on local trust policy. Mr Julian Shah noted the most litigious areas of andrology, with focus on cosmesis following circumcisions. Therefore serving a reminder on the importance of good consent to manage patients’ expectations.

1.3

In the Dragons’ Den, like the TV show, junior urologists pitched their ideas for collaborative research projects, to an expert panel. This year’s panel was made up of – Mark Emberton, Ian Pearce, and Graeme MacLennan. The session was chaired by Veeru Kasivisvanathan, Chair of the BURST Research Collaborative.

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Eventual winner Ben Lamb, a trainee from London, presented “Just add water”. The pitch was for an RCT to investigate the efficacy of water irrigation following TURBT against MMC in reducing tumour recurrence. Ben proposed that water, with its experimental tumouricidal properties, might provide a low risk, low cost alternative as an adjuvant agent following TURBT. Judges liked the scientific basis for this study and the initial planning for an RCT. The panel discussed the merits of non-inferiority vs. superiority methodology, and whether the team might compare MMC to MMC with the addition of water, or water instead of MMC. They Dragons’ suggested that an initial focus group to investigate patients’ views on chemotherapy might help to focus the investigation and give credence to the final research question, important when making the next pitch- to a funding body, or ethics committee.

Other proposals were from Ryad Chebbout, working with Marcus Cumberbatch, an academic trainee from Sheffield. Proposing to address the current controversy over the optimal surgical technique for orchidopexy following testicular torsion. His idea involved conducting a systematic review, a national survey of current practice followed by a Delphi consensus meeting to produce evidence based statement of best practice. The final presentation was from Sophia Cashman, East of England Trainee for an RCT to assess the optimal timing for a TWOC after urinary retention. The panel liked the idea of finally nailing down an answer to this age-old question.

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Waking up on Tuesday with England out of the European football cup as well as Europe the conference got underway with an update from the PROMIS trial (use of MRI to detect prostate cancer). Early data shows that multi-parametric MRI may be accurate enough to help avoid some prostate biopsies.

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The SURG meeting provided useful information for trainees, with advice on progressing through training and Consultant interviews. A debate was held over run through training, which may well be returning in the future. The Silver cystoscope was awarded to Professor Rob Pickard voted for by the trainees in his deanery, for his devotion to their training.
Wednesday continued the debate on medical expulsion therapy (MET) for ureteric stones following the SUSPEND trial. Most UK Urologists seem to follow the results of the trial and have stopped prescribing alpha blockers to try and aid stone passage and symptoms. However the AUA are yet to adopt this stance and feel that a sub analysis shows some benefit for stones >5mm, although this is not significant and pragmatic outcomes. Assistant Professor John Hollingsworth (USA) argued for MET, with Professor Sam McClinton (UK) against. A live poll at the end of the session showed 62.9% of the audience persuaded to follow the SUSPEND trial evidence and stop prescribing MET.

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In the debate of digital versus fibreoptic scopes for flexible ureteroscopy digital triumphed, but with a narrow margin.

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In other updates and breaking news it appears that BCG is back! However during the shortage EMDA has shown itself to be a promising alternative in the treatment of high grade superficial bladder cancer.
The latest BAUS nephrectomy data shows that 90% are performed by consultant, with 16 on average per consultant per year. This raises some issues for registrar training, however with BAUS guidelines likely to suggest 20 as indicative numbers this is looking to be an achievable target for most consultants. Robotic advocates will be encouraged, as robotic partial nephrectomy numbers have overtaken open this year. The data shows 36% of kidney tumours in the under 40 years old are benign. Will we have to consider biopsying more often? However data suggests we should be offering more cytoreductive nephrectomies, with only roughly 1/10 in the UK performed compared to 3/10 in the USA.

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The andrology section called for more recruitment to The MASTER trial (Male slings vs artificial urinary sphincters), whereas the OPEN trial has recruited(open urethroplasty vs optical urethotomy). In the treatment of Peyronie’s disease collagenase has been approved by NICE but not yet within the NHS.

Endoluminal endourology presentation showed big increases in operative numbers with ureteroscopy up by 50% and flexible ureteroscopy up by 100%. Stents on strings were advocated to avoid troubling stent symptoms experienced by most patients. New evidence may help provide a consensus on defining “stone free” post operation. Any residual stones post-operatively less than 2mm were shown to pass spontaneously and therefore perhaps may be classed as “stone free”.

Big changes seem likely in the treatment of benign prostatic hyperplasia, with a race to replace the old favorite TURP. Trials have of TURP (mono and bipolar) vs greenlight laser are already showing similar 2 year outcomes with the added benefit of shorter hospital stays and less blood loss. UROLIFT is an ever more popular alternative with data showing superiority to TURP in lifestyle measures, likely because it preserves sexual function, and we are told it can be performed as a 15 minute day case operation. The latest new therapy is apparently “Aquabeam Aquablation”, using high pressured water to remove the prostate. Non surgical treatments are also advancing with ever more accurate super selective embolisation of the prostatic blood supply.

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This year all accepted abstracts were presented in moderated EPoster sessions. The format was extremely successful removing the need for paper at future conferences? A total of 538 abstracts were submitted and 168 EPosters displayed. The winner of best EPoster was P5-5 Altaf Mangera: Bladder Cancer in the Neuropathic Bladder.

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The best Academic Paper winner was Mark Salji of the CRUK Beatson institute, titled “A Urinary Peptide Biomarker Panel to Identify Significant Prostate Cancer”. Using capillary electrophoresis coupled to mass spectrometry (CE-MS) they analysed 313 urine samples from significant prostate cancer patients (Gleason 8-10 or T3/4 disease) and low grade control disease. They identified 94 peptide urine biomarkers which may provide a useful adjunct in identifying significant prostate cancer from insignificant disease.

The Office of Education offered 20 courses. Popular off-site courses were ultrasound for the Urologist, at Broadgreen Hospital, a slightly painful 30 min drive from the conference centre. However well worth the trip, delivered by Radiology consultants this included the chance to scan patients volunteers under guidance, with separate stations for kidneys, bladder and testicles and learning the “knobology” of the machines.

Organised by Tamsin Greenwell with other consultant experts in female, andrology and retroperitoneal cancer, a human cadaveric anatomy course was held at Liverpool university. The anatomy teaching was delivered by both Urology consultants and anatomists allowing for an excellent combination of theory and functional anatomy.

BAUS social events are renowned and with multiple events planned most evenings were pretty lively. The official drinks reception was held at the beautiful Royal Liver Building. The venue was stunning with great views over the waterfront and the sun finally shining. Several awards were presented including the Gold cystoscope to Mr John McGrath for significant contribution to Urology within 10 years appointment as consultant. The Keith Yeates medal was awarded to Mr Raj Pal, the most outstanding candidate in the first sitting of the intercollegiate specilaity examination, with a score of over 80%.

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During the conference other BAUS awards presented include the St Peter’s medal was awarded to Margeret Knowles, Head of section of molecular oncology, Leeds Institute of Cancer and Pathology, St James University hospital Leeds. The St Paul’s medal awarded to Professor Joseph A. Smith, Vanderbilt University, Nashville, USA. The Gold medal went to Mr. Tim Terry, Leicester General Hospital.

An excellent industry exhibition was on display, with 75 Exhibiting Companies present. My personal fun highlight was a flexible cystoscope with integrated stent remover, which sparked Top Gear style competiveness when the manufacturer set up a time-trial leaderboard. Obviously this best demonstrated the speed of stent removal with some interesting results…

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Social media review shows good contribution daily.

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Thanks BAUS a great conference, very well organised and delivered with a great educational and social content, looking forward to Glasgow 2017! #BAUS2017 #Glasgow #BAUSurology

Nishant Bedi

Specialist Training Registrar North West London 

Twitter: @nishbedi

 

Guideline of guidelines: follow-up after nephrectomy for renal cell carcinoma

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RCC folowup

 

Abstract

The purpose of this article was to review and compare the international guidelines and surveillance protocols for post-nephrectomy renal cell carcinoma (RCC). PubMed database searches were conducted, according to the PRISMA statement for reporting systematic reviews, to identify current international surveillance guidelines and surveillance protocols for surgically treated and clinically localized RCC. A total of 17 articles were reviewed. These included three articles on urological guidelines, three on oncological guidelines and 11 on proposed strategies. Guidelines and strategies varied significantly in relation to follow-up, specifically with regard to the frequency and timing of radiological imaging. Although there is currently no consensus within the literature regarding surveillance protocols, various guidelines and strategies have been developed using both patient and tumour characteristics.

 

Access the full article

Article of the week: Restored renal function after RN

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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 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. Chung discussing his paper.

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

Trends in renal function after radical nephrectomy: a multicentre analysis

Jae S. Chung1, Nak H. Son2, Seok-Soo Byun6, Sang E. Lee6, Sung K. Hong6, Chang W. Jeong6, Sang C. Lee6, Dong-Wan Chae7, Won S. Choi8, Yong H. Park3, Sung H. Hong4, Yong J. Kim9 and Seok H. Kang5

1Department of Urology, Inje University College of Medicine, Haeundae Paik Hospital, Busan, 2Department of Biostatistics, Yonsei University College of Medicine, 3Department of Urology, Seoul National University Hospital, 4Department of Urology, Seoul St. Mary’s Hospital, 5Department of Urology, Korea University Anam Hospital, Seoul, 6Departments of Urology and 7Internal Medicine, Seoul National University Bundang Hospital, Seongnam, 8Choi Won Suk Urology Clinic, Yongin, and 9Department of Urology, Chungbuk National University Hospital, Cheongju, Korea

Read the full article
OBJECTIVE

• To evaluate serial changes in renal function by investigating various clinical factors after radical nephrectomy (RN).

PATIENTS AND METHODS

• The study population consisted of 2068 consecutive patients who were treated at multiple institutions by RN for renal cortical tumour without metastasis between 1999 and 2011.

• We measured the serial change in estimated glomerular filtration rate (eGFR) and clinical factors during a 60-month follow-up period.

• The changes in eGFR over time were analysed according to baseline eGFR (eGFR ≥60 and 15–59 mL/min/1.73m2) using a linear mixed model.

• The independent prognostic value of various clinical factors on the increase in eGFR was ascertained by multivariate mixed regression model.

RESULTS

• Overall, there was a subsequent restoration of renal function over the 60 months.

• The slope for the relationship between the eGFR and the time since RN was 0.082 (95% confidence interval [CI] 0.039–0.104; P < 0.001) and 0.053 (95% CI 0.006–0.100; P = 0.038) in each baseline group, indicating that each month after RN was associated with an increase in eGFR of 0.082 and 0.053 mL/min/1.73m2, respectively.

• When we analysed renal function based on various factors, postoperative eGFR of patients with diabetes mellitus, old age (≥70 years) or a preoperative eGFR of <30 mL/min/1.73 m2, was decreased or maintained at a certain level without any improvement in renal function.

• Preoperative predictors of an increase in eGFR after RN were young age, no DM, no hypertension, a preoperative eGFR of ≥30 mL/min/1.73m2 and time after surgery (≥36 months).

CONCLUSIONS

• Renal function recovered continuously during the 60-month follow-up period after RN.

• However, the trends in functional recovery change were different according to various clinical factors and such information should be discussed with patients when being counselled about their treatment for renal cell carcinoma (RCC).

 

Read Previous Articles of the Week

 

Editorial: Renal functional recovery after radical nephrectomy

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In their publication ‘Trends in renal function after radical nephrectomy: a multicentre analysis’, Chung et al. [1] suggest that after radical nephrectomy (RN), renal functional recovery in patients who have RCC occurs even in states of baseline renal functional compromise (pre-existing stage III chronic kidney disease, CKD). These findings bolster other recent reports, which suggest that surgically induced CKD may not be associated with the same degree of renal functional decline as CKD that may be caused by medical factors [2, 3]. While the incidence of de novo stage III CKD (36.1%) and delta estimated GFR between preoperative and postoperative values are lower than reported by most other groups, which may be attributable to national and demographic trends that are different from North American and European trends [2-4], the findings are nonetheless important and show that in the short-to-intermediate term (median follow up of 33 months) continued renal functional stabilisation and recovery occurs after RN. Also, performing a RN in a patient does not sentence him or her to invariable or inevitable renal functional decline in the short-to-intermediate term. Furthermore, they establish, in the short-to-intermediate term at least, a reasonable timeline of renal functional recovery for patient counselling and physician expectations in the postoperative follow-up period. Interestingly, and perhaps more disturbingly, the authors noted minimal and no functional recovery in the elderly and diabetic groups, underlying the importance for consideration of nephron-sparing approaches in these higher risk subgroups, even in the setting of normal renal function, and particularly with a lower risk lesion, e.g. a clinical T1a renal mass [5]. What we are missing from this analysis are longer term data, and a more thorough analysis of the incidence and impact of potential metabolic and cardiovascular sequelae during this period [4, 6], and a comparative analysis that examines the timeline of renal functional recovery after partial nephrectomy. Because of these reasons, the reader should be cautioned not to over-interpret these findings, and to conclude that because RN is associated with renal functional recovery, performing a RN may not pose increased long-term risk compared with a nephron-sparing method, particularly in a patient with pre-existing medical drivers towards CKD (diabetes, obesity, hyperlipidaemia, etc.). These findings are nonetheless important and provocative, and should spur further investigation and may provide an important adjunct in the counselling of patients about the functional impact of RN.

Read the full article

Ithaar H. Derweesh
Department of Urology, University of California San Diego Health System, La Jolla, CA, USA

References

  1. Chung JS, Son NH, Byun SS et al. Trends in renal function after radical nephrectomy: a multicentre analysis. BJU Int 2014; 113:408–415
  2. Van Poppel H, Da Pozzo L, Albrecht W et al. A prospective, randomised EORTC intergroup phase 3 study comparing the oncologic outcome of elective nephron-sparing surgery and radical nephrectomy for low-stage renal cell carcinoma. Eur Urol 2011; 59:543–552
  3. Lane BR, Campbell SC, Demirjian S, Fergany AF. Surgically induced chronic kidney disease may be associated with a lower risk of progression and mortality than medical chronic kidney disease. J Urol 2013; 189: 1649–1655
  4. Sun M, Bianchi M, Hansen J et al. Chronic kidney disease after nephrectomy in patients with small renal masses: a retrospective observational analysis. Eur Urol 2012; 62: 696–703
  5. Campbell SC, Novick AC, Belldegrun A et al. Guideline for management of the clinical T1 renal mass. J Urol 2009; 182:1271–1279
  6. Woldrich J, Mehrazin R, Bazzi WM et al. Comparison of rates and risk factors for development of anaemia and erythropoiesis-stimulating agent utilization after radical or partial nephrectomy. BJU Int 2012; 109: 1019–1025

 

Video: Trends in renal function after RN

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Trends in renal function after radical nephrectomy: a multicentre analysis

Jae S. Chung1, Nak H. Son2, Seok-Soo Byun6, Sang E. Lee6, Sung K. Hong6, Chang W. Jeong6, Sang C. Lee6, Dong-Wan Chae7, Won S. Choi8, Yong H. Park3, Sung H. Hong4, Yong J. Kim9 and Seok H. Kang5

1Department of Urology, Inje University College of Medicine, Haeundae Paik Hospital, Busan, 2Department of Biostatistics, Yonsei University College of Medicine, 3Department of Urology, Seoul National University Hospital, 4Department of Urology, Seoul St. Mary’s Hospital, 5Department of Urology, Korea University Anam Hospital, Seoul, 6Departments of Urology and 7Internal Medicine, Seoul National University Bundang Hospital, Seongnam, 8Choi Won Suk Urology Clinic, Yongin, and 9Department of Urology, Chungbuk National University Hospital, Cheongju, Korea

Read the full article
OBJECTIVE

• To evaluate serial changes in renal function by investigating various clinical factors after radical nephrectomy (RN).

PATIENTS AND METHODS

• The study population consisted of 2068 consecutive patients who were treated at multiple institutions by RN for renal cortical tumour without metastasis between 1999 and 2011.

• We measured the serial change in estimated glomerular filtration rate (eGFR) and clinical factors during a 60-month follow-up period.

• The changes in eGFR over time were analysed according to baseline eGFR (eGFR ≥60 and 15–59 mL/min/1.73m2) using a linear mixed model.

• The independent prognostic value of various clinical factors on the increase in eGFR was ascertained by multivariate mixed regression model.

RESULTS

• Overall, there was a subsequent restoration of renal function over the 60 months.

• The slope for the relationship between the eGFR and the time since RN was 0.082 (95% confidence interval [CI] 0.039–0.104; P < 0.001) and 0.053 (95% CI 0.006–0.100; P = 0.038) in each baseline group, indicating that each month after RN was associated with an increase in eGFR of 0.082 and 0.053 mL/min/1.73m2, respectively.

• When we analysed renal function based on various factors, postoperative eGFR of patients with diabetes mellitus, old age (≥70 years) or a preoperative eGFR of <30 mL/min/1.73 m2, was decreased or maintained at a certain level without any improvement in renal function.

• Preoperative predictors of an increase in eGFR after RN were young age, no DM, no hypertension, a preoperative eGFR of ≥30 mL/min/1.73m2 and time after surgery (≥36 months).

CONCLUSIONS

• Renal function recovered continuously during the 60-month follow-up period after RN.

• However, the trends in functional recovery change were different according to various clinical factors and such information should be discussed with patients when being counselled about their treatment for renal cell carcinoma (RCC).

 

Article of the week: SEER shows no benefit from LND in RCC

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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 from Maxine Sun discussing her paper.

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

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.

Read the full article
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.

 

Read Previous Articles of the Week

 

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

Read the full article

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.

Read the full article
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 week: What predicts cancer-specific survival after renal cancer recurrence?

/by

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

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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

/1 Comment/by

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

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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
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