Tag Archive for: Editorial

You are here: / Editorial

Posts

Editorial: Is surgery a never ending learning process?

/by

The concept of the learning curve is one of the most important issues in surgery and also one of the most overlooked. In the present issue of BJUI, Abboudi et al. [1] present an interesting review paper evaluating the concept of the learning curve in urological procedures. Specifically, the authors have conducted a methodologically consistent systematic review on the literature focused on the learning curve of some urological procedures, including mainly radical prostatectomy (RP), robot-assisted partial nephrectomy (RAPN) and percutaneous nephrolitotomy [1]. Surprisingly, nothing was available for BPH treatments, which are among the most prevalent urological procedures. 

Most of the studies are focused on robot-assisted RP (RARP), but the available literature is of poor methodological quality, including mainly surgical series evaluating a limited number of surgeons, with a heterogeneous selection of outcomes from which to study the learning curve and a focus on short-term outcomes. Conversely, the literature on retropubic RP or laparoscopic RP is of higher quality, including a few very large multi-institutional studies encompassing the performances of several surgeons (reference nos. 24, 26, 29 and 30 in the review) and adopting sophisticated statistical methodology; however, the current interest for these procedures is quite limited, RARP being more commonly preferred. With the above-mentioned limitations in mind, what we have learnt is that RARP operating time plateaus after 50–200 cases, positive surgical margin (PSM) rates after 50–1600 cases, and continence and potency after 200 cases [1]. Such data are only partially in line with the findings of a recent prospective Australian study [2], not included in the present systematic review, which evaluated the learning curve with RARP of a high-volume open surgeon (>3000 retropubic RPs performed before the study beginning). In that study, Thompson et al. [2] demonstrated that performances with RARP surpassed those with retropubic RP after ∼100 cases for sexual function scores and PSM rates in pT2 cancers, whereas ∼150 cases were needed to reach the same target with urinary function scores. Moreover, RARP performances kept on improving, with sexual and urinary scores plateauing after 600–700 and 700–800 cases, respectively. Similarly, with regard to PSMs, it was demonstrated that PSM rates in pT2 and pT3–4 cancers plateaued after 400–500 and 200–300 cases, respectively [2]. Although improvement is likely, it is not clear how much these performances might improve with further extension of the caseload. 

Taken together, those data suggest that even with robotic assistance, a high volume of cases is strongly associated withimproving oncological and functional outcomes after RARP. This is not an extraordinarily original concept, but implies that the daVinci platform, by itself, cannot guarantee excellent surgical quality and that the relevance of the surgeon is as high as ever. 

Limited data are available on other major robotic procedures, such as RAPN and robot-assisted radical cystectomy (RARC). Specifically, 20–75 cases are thought to be needed to observe a plateau in warm ischemia time (WIT) during RAPN, which is in line with our previous findings demonstrating a continuous decrease in WIT during the first 50 cases [3]. Similarly, 20–30 cases are supposed to be needed to achieve acceptable operating times, lymph node yields and PSM rates after RARC; however, those findings do not take in account the burden of robotic experience achieved with RARP before embarking in RARC, which is clearly a major issue [4]. 

Considering that the improvements in performances along the learning curve exceeded any effect sizes we might reasonably expect from a novel drug [5], it is clear that any attempt to centralise treatments for complex procedures in high-volume centres with high-volume surgeons should be attempted. Obviously, that is a very critical target, which is hard to achieve in many realities. In parallel, interventions to improve the performance of surgeons in order to,reduce the learning curve are mandatory. For example, fellowship-trained RARP surgeons have been shown to outperform experienced open or laparoscopic surgeons moving to RARP without specific training [6,7]. For those surgeons for whom fellowship is unfeasible or unpractical, structured courses with integration of simulation, dry laboratory, wet laboratory and da Vinci modular training, for example, using the model of the recently concluded European Robotic Urology Society Pilot Study, can significantly ease the first steps of the learning curve, reducing patients risk. In parallel, intensive courses focused on specific procedures could help those surgeons who had completed the initial steps of their learning curve to master the specific technical details necessary to improve outcomes.

Read the full article

Alexander Mottrie*† and Giacomo Novara†‡

*OLV Vattikuti Robotic Surgery Institute and † Department of Urology, OLV Hospital Aalst, Aalst, Belgium and ‡ Department of Surgery, Oncology and Gastroenterology, Urology Clinic University of Padua, Padua, Italy

References

1 Abboudi H, Khan MS, Guru KA et al. Learning curves for urological procedures: a systematic review. BJU Int 2014; 114: 617–29

2 Thompson JE, Egger S, Böhm M et al. Superior quality of life and improved surgical margins are achievable with robotic radical prostatectomy after a long learning curve: a prospective single-surgeon study of 1552 consecutive cases. Eur Urol 2014; 65: 521–31

3 Mottrie A, De Naeyer G, Schatteman P et al. Impact of the learning curve on perioperative outcomes in patients who underwent robotic partial nephrectomy for parenchymal renal tumours. Eur Urol 2010; 58: 127–32

4 Hayn MH, Hellenthal NJ, Hussain A et al. Does previous robot-assisted radical prostatectomy experience affect outcomes at robot-assisted radical cystectomy? Results from the International Robotic Cystectomy Consortium. Urology 2010; 76: 1111–6

5 Vickers AJ. What are the implications of the surgical learning curve? Eur Urol 2014; 65: 532–3

6 Kwon EO, Bautista TC, Jung H et al. Impact of robotic training onsurgical and pathologic outcomes during robot-assisted laparoscopicradical prostatectomy. Urology 2010; 76: 363–8

7 Leroy TJ, Thiel DD, Duchene DA et al. Safety and peri-operative outcomes during learning curve of robot-assisted laparoscopicprostatectomy: a multi-institutional study of fellowship-trainedrobotic surgeons versus experienced open radical prostatectomysurgeons incorporating robot-assisted laparoscopic prostatectomy. J Endourol 2010; 24: 1665–9

 

Editorial: Patient-reported outcomes – a force for clinical improvement or another way for ‘big brother’ to survey clinicians?

/by

In the 19th century Lord Kelvin wrote, ‘If you cannot measure it, you cannot improve it’. Since then clinical improvement has often been about measuring outcomes to determine what elements of healthcare are working well and what can be improved. The early studies of antisepsis and surgical technique had endpoints, which were measured by doctors deciding whether a wound infection, cancer recurrence or even death had occurred. These outcomes were usually discrete with little room for describing states between success and failure.

In this era whether the patient perceived that the treatment had been successful or not was irrelevant to the ‘success’ of treatment providing that the medical world agreed that the treatment had been a success. As treatments have become more established and the medical and pharmaceutical world has become more patient focussed, interest has increased in how patients report the outcome of treatment, often using questionnaires.

The pioneers of this work were mainly psychiatrists concerned about patient anxiety and depression [1] and clinical oncologists, aware that multimodal chemoradiotherapy treatments, which might in many cases be offered with palliative rather than curative intent, had the potential to cause a net loss in quality of life even if patients lived a short time longer on treatment.

As these patient-reported outcome measures (PROMs) became more commonly used in clinical trials, their focus has extended to quite specific outcomes, such that in the current era it is unusual to see papers on LUTS or erectile function presented that do not use validated PROMs, such as the IPSS [2] or International Index of Erectile Function (IIEF) [3].

The current era of research is starting to make new use of the data sources that are useful both as absolute values relating to the severity of symptoms but also particularly in measuring change in level of symptoms. Hard outcomes, such as death from cancer, have been found to be related to patient reported quality of life at presentation [4].

Clinicians are now starting to develop the necessary skills to analyse PROMs. In this setting Talcott et al. [5] have used PROM data to identify unexpected variances in symptomatic outcome after prostate brachytherapy. This was an unexpected post hoc analysis of a difference in outcomes between the two control groups in a study. It found that there was a significant difference in outcome between patients who had received an implant in two centres, which might have been expected to have similar outcomes. Analysis of differences in the implant technique in the two institutions suggested that the use of a urethral catheter to clearly visualise the urethra might be the difference and modification of this part of the technique resulted in similar PROMS outcomes in both institutions.

This is a novel quality improvement approach, which may become more widespread as institutions more frequently collect, analyse and present their PROMS. The bio-informatics skills needed to analyse this type of data meaningfully may become a greater part of everyday practice in the modern era, especially for the ‘index’ most common operations in surgical specialities. It would be interesting to see what a similar approach would produce if variance in PROMs after transurethral prostate surgery were analysed between centres in the UK and USA. Organisations with a track record for effective data analysis and reporting such as Dr Foster will be watching this evolve.

Read the full article

Alastair Henderson

Maidstone and Tunbridge Wells NHS Trust, Department of Urology, Maidstone Hospital, Maidstone, Kent, UK

References

1 Zigmond AS, Snaith RP. The Hospital Anxiety and Depression Scale. Acta Psychiat Scand 1983; 67: 361–70

2 Barry MJ, O’Leary MP. Advances in benign prostatic hyperplasia. The developmental and clinical utility of symptom scores. Urol Clin North Am 1995; 22: 299–307

3 Cappelleri JC, Rosen RC, Smith MD, Mishra A, Osterloh IH. Diagnostic evaluation of the erectile function domain of the International Index of Erectile Function. Urology 1999; 54: 346–51

4 Montazeri A. Quality of life data as prognostic indicators of survival in cancer patients: an overview of the literature from 1982 to 2008. Health Qual Life Outcomes 2009; 7: 102

5 Talcott JA, Manola J, Chen RC et al. Using patient-reported outcomes to assess and improve prostate cancer brachytherapy. BJU Int 2014; 114: 511–6

Editorial: Robot-assisted pyeloplasty in children

/by

The authors of the study on robot-assisted pyeloplasty in this issue of BJUI have carried out an excellent review of the current data on this common paediatric urology procedure [1]. Although the analysis involves small case numbers and series for meta-analysis, the data are useful for current practice. It may be worth waiting another 5 years to review the data again, by which time the learning curve for most of the surgeons will be over, and a true representation of practice and a comparison against the established standard open surgery, which has been established over decades, can be reported. The training of next-generation surgeons needs to be factored into this process, which is critically important.

With the different methods of critical evaluation presently available, we may be able to draw some conclusions from the results of robot-assisted pyeloplasty, but the problem that remains is the inconsistency of individual reports in terms of outcome and complications. We surgeons need to work on developing a consensus model for the evaluation of each procedure so that uniformity exists. The financial implications of new technology will always be higher than expected, but with a greater number of users and competitive producers the cost will be remarkably reduced. As paediatric surgeons, we do not know the unseen benefits of robot-assisted pyeloplasty, but the children’s families have a positive perception of post-surgical aesthetic appearance, and may also have some human capital gains in terms of reduced childcare expenditure. The paradigm shift to a digital era of surgery is here to stay, with safety and refinements to technology being universally available to all children.

Read the full article

Mohan S. Gundeti

BJUI Consulting Editor, Paediatrics, The Medicine University of Chicago, Chicago, IL, USA

References

1. Cundy TP, Harling L, Hughes-Hallett A et al. Meta analysis of robot-assisted vs conventional laparoscopic and open pyeloplasty in children. BJU Int 2014; 114: 582–94

Read more articles of the week

 

 

Paediatric urology in the BJUI

/1 Comment/by
The BJUI and the Editorial team are committed to the publication of high-quality and highly citable articles concerning translational science for the International Paediatric Urology Community. We encourage authors to submit original and outstanding work for publication that can influence clinical practice or introduce innovative new care methods for children across the world.
In addition to valuable contributions, the reviewers’excellent review process ensures the best publications. Although, impact factor is an important attribute for a journal; the real true value resides with its ability to make paradigm shifts and bring innovative care to children’s lives.

On this note we have included the best three articles in the ‘Paediatrics’ section in this month’s issue.

Cundy et al. [1] from London (UK), have to be commended for the thoughtful meta-analysis of robot-assisted pyeloplasty (RAP).This is an early, but, timely analysis of our current practice of different approaches to paediatric pyeloplasty. The primary outcomes were not significantly different for the open, robotic or laparoscopic approaches. This is not surprising ,as the surgeons that used these new approaches have been proficient with their traditional approaches and have embraced the newer techniques with caution. RAP had a distinct advantage of reduced analgesia and length of hospital stay compared with the traditional open approaches, and this will probably drive the adoption of the newer approaches even at the expense of increased cost. Hopefully, the cost issue will be transient; as the new technology becomes increasingly widespread the cost should level out. Randomised clinical trials may be an answer to newer treatment adoption,but this may not be possible in all scenarios – hence a prospective comparative series may answer the question, with some human factor bias [2]. The advantage of ergonomic comfort and a reduced learning curve for surgeons performing these reconstructive procedures using the robotic approach,as mentioned by the authors,has the benefit of reducing professional health hazards and saving on human capital. Unfortunately, this has never been considered or measured, although it is an important aspect.

Suer et al. [3] from Turkey, have analysed their anti-reflux surgery series in children using the open approach to predict complications in a multivariate analysis. The utmost factor is bladder dysfunction, e.g.bladder-bowel dysfunction, dysfunctional elimination syndrome or dysfunctional voiding. Over the years paediatric urologists have found this to be associated with VUR and poor outcomes after surgery. Extreme caution has to be taken when deciding to perform surgery in this group, as theVUR may be secondary and surgery may not be warranted at all.Ureteric tapering or tailoring of the dilated ureter is another factor for poor outcomes, which can be attributed to the poor vascularity of chronically dilated ureters. This practice has been based on the physics of Paquin’s law.Unfortunately, we do not have evidence of outcomes without this reduction plasty on these ureters. The authors have also emphasised the limitations of the current adult Clavien system of classification used for grading [4], which has pitfalls and does not describe the complications well either in the paediatric population. It is an appeal to the paediatric urology community for further work to be done to produce a standardised grading system for use in paediatric cases.

Dangle et al. [5] from The University of Chicago have attempted to describe extravesical robotic ureteric re-implantation for VUR in children. The technique of re-implantation has not been described well to date, although there have been a few outcome reports with variable success rates. This explains the fact there may not be uniformity in this technique and/or the learning curve. The surgery itself is challenging because of the close proximity of important anatomical structures within a confined space, and the risk of ureteric damage with improper handling is unforgiving. The video describes their current modified technique with important surgical steps for adoption. The success rate for resolution is still, not on a par with open surgery, but there were no complications. The fine balance between success and complications needs to be defined for incorporation into the paediatric urological armamentarium.

Moving forward:

‘With availability of advanced automated instruments to replace manual labour, if as a society we prefer this at an increased cost, then why not on the same philosophy adopt these new technologies in the surgical realm with proper training and safety to reduce the morbidity and achieve at par results?’.

and

‘The surgical dogma of practice needs to be challenged with evidence-based outcomes to move ahead’.

Conflict of Interest

None declared.

Mohan S. Gundeti, MD, MCh, FEBU, FRCS, FEAPU

BJUI Consulting Editor–Paediatrics, The University of Chicago Medicine, Chicago, IL, USA e-mail: [email protected]

References

1            Cundy TP, Harling L, Hughes-Hallett A et al. Meta-analysis of robot-assisted vs conventional laparoscopic and open pyeloplasty in children. BJU Int 2014; 114: 582–94

2            Orvieto MA, Large M, Gundeti MS. Robotic paediatric urology.BJU Int 2012; 110: 2–13

3            Suer E, Ozcan C, Mermerkaya M et al. Can factors affecting complication rates for ureteric re-implantation be predicted? Use of the modified Clavien classification system in a paediatric population. BJU Int 2014; 114: 595–600

4            Clavien PA, Barkun J, de Oliveira ML et al. The Clavien-Dindo classification of surgical complications: five-year experience.Ann Surg 2009; 250: 187–96

5            Dangle PP, Shah A, Gundeti MS. Robot-assisted laparoscopic ureteric reimplantation:extravesical technique. BJU Int 2014; 114: 630–2

© 2014 The Author 468 BJU International © 2014 BJU International

Editorial: A call for the international adoption of penile specialist networks

/by

The recent article by Tang et al. [1] from the Christie Hospital in Manchester raises an interesting question. The urological cancer plan for England and Wales specifies that review of the pathology of prostate and high-risk superficial bladder cancer should take place as part of the referral process for these cases to specialist pelvic cancer teams, but the penile pathway does not indicate that this is necessary [2]. The Royal College of Pathologists [3] also specifies the need for expert review and/or double reporting in other rare cancers and dysplasias, but does not yet specify this for penile cancers.

Penile cancers are rare, with 600 new cases diagnosed in the UK per year. They are almost invariably squamous cell carcinomas, which also occur at other sites including the lung, upper aerodigestive tract and skin. This may lead some pathologists to assume that they are similar and do not need second opinion or review; however, the subtypes of squamous cell carcinoma that occur on the penis are not common elsewhere, include basaloid, warty and verrucous carcinomas [4], and are not always recognized by general pathologists. The anatomy of the penis is challenging and the identification of invasion of urethra, corpus spongiosum and corpus cavernosum is important in accurate staging. Penile cancers have their own TNM system. TNM7, published in 2010 [5], recognises the importance of grading and different stage groups on prognosis.

Our own experience at St George’s Hospital in South London mirrors that of the Christie Hospital in North West England. Our practice from the outset of the establishment of our supra-regional penile centre was to review outside pathology in the setting of our specialist multidisciplinary meeting to devise a management plan for each patient. We also found that our reviewed cases were more likely to be under-graded and that staging was frequently inaccurate if it was attempted at all. Our original audit was presented at the BAUS annual meeting in 2005. We repeated the audit in 2008 after the publication of the Royal College of Pathologists guidelines on the reporting of penile cancer and found no improvement (unpublished data).

An average urological pathologist in a non-specialist centre in the UK will only see 1–3 cases of penile cancer per year and will have little opportunity or incentive to gain expertise in this area. Although second opinion services through the supra-networks are freely available, these are not always sought, perhaps because of time pressures and the mistaken impression that penile cancers are like those of other sites. There is also a lack of awareness of new entities, for example, differentiated penile intraepithelial neoplasia (PeIN) and subtypes of undifferentiated PeIN. There has been a recent change in nomenclature, whereby all morphological types of squamous carcinoma in situ and dysplasias are now classified within PeIN [6].

The supra-network of penile centres in the UK has allowed a small group of pathologists to gain expertise in the reporting of penile cancer in a specialist clinical setting, and has produced a group of pathologists with a special interest in this type of tumour, all of whom are seeing at least 25 new cases per year. Many centres are seeing more, with our own centre managing 126 new cases in 2012.

In 2008 we formed a UK-wide group of specialist penile pathologists (the Hobnobs) which meets annually to exchange both clinical and research information and to discuss individual cases. Members of this group are currently updating the Royal College of Pathologists penile guidelines [3]. These will advise central review, but we recognize we are writing them mainly for specialist pathologists to ensure consistent and high-quality assessment of penile cancer to inform the penile cancer team.

In the UK, expert pathological review of penile cancer is already the norm for the penile supra-networks, but it would be difficult to make this the global standard for several reasons. Sub-specialization in penile cancer management is not widely practised outside Britain and there are few specialist high-volume centres, with some notable exceptions in Europe and the USA. Without clinical sub-specialization it is difficult for pathologists to develop an interest and sufficient expertise to offer an expert second opinion because the numbers seen by any individual pathologist will be too small.

The UK penile supra-network system works well and has led to a group of pathologists developing an interest in this area simply because they are seeing a large number of such cases and working with dedicated clinical teams. Penile supra-networks should be adopted worldwide. Following this, a group of expert and experienced pathologists will ultimately be developed, who can offer a central review and expert second opinion service, as has happened over the last 10 years in the UK.

Read the full article

Catherine M. Corbishley
Department of Cellular Pathology, St George’s Healthcare NHS
Trust, London, UK

References

1. Tang V, Clarke L, Gall Z et al. Should centralised histopathological review in penile cancer be the global standard? BJU Int 2014;114: 340–343

2. Manual for Cancer services. Urology measures Version 2.1. NHS National Cancer Peer Review Programme 2011 and Evidence guide for Urology Supraregional Penile MDT NHS National Cancer Peer Review Programme 2010.

3. Royal College of Pathologists. Cancer Datasets and Tissue Pathways. Available at: https://www.rcpath.org/publications-media/publications/datasets.

4. Epstein JI, Cubilla AL, Humphrey PA. Tumours of the Prostate Gland, Seminal Vesicles, Penis and Scrotum. American Registry of Pathology, Washington DC published in collaboration with the Armed Forces Institute of Pathology, 2011, 405–612

5. Gospodarowicz MK (section editor, Genitourinary Tumours). TNM classification of malignant tumours (7th edition) penis. In Edge SB,Byrd DR, Compton CC Fritz AG, Greene FL, Trotti A eds, AJCC Cancer Staging Manual, 7th edn. New York: Springer, 2010:447–455

6. Velazquez EF, Chaux A, Cubilla AL. Histologic classification of penile intraepithelial neoplasia. Semin Diagn Pathol 2012; 29: 96–102

Read more articles of the week

Editorial: Perioperative aspirin: To give or not to give?

/by

As the population ages and life expectancy increases, one may safely assume that more men will be diagnosed with diseases of the elderly such as prostate cancer. In the USA, it is estimated that the number of older adults (≥65 years old) will double between 2010 and 2030, contributing to a 45% increase in cancer incidence [1]. Also, it is likely that these older patients will present with multiple comorbidities, commonly described as ‘multimorbidity’ in the contemporary medical literature, including chronic cardiac and pulmonary conditions requiring multidisciplinary medical management.

Hence, the present study by Leyh-Bannurah et al. [2] examining the peri-operative use of aspirin in patients undergoing radical prostatectomy (RP) is a timely and important contribution, and may very well influence our clinical decision-making regarding the perioperative management of the anti-coagulated patient. Their results show that perioperative continuation of aspirin made no difference in peri and postoperative outcomes following RP. Previous studies have assessed the effect of aspirin continuation in patients undergoing minimally invasive RP, but the present study is the first to evaluate the effect of aspirin continuation in patients undergoing minimally invasive and open RP at a high-volume tertiary centre. Studies from other surgical specialties evaluating the role of anti-platelet therapy and its timing before surgery have shown conflicting results. The study by Park et al. [3], looking at discontinuation of aspirin for ≥7 days vs <7 days before surgery in patients undergoing lumbar spinal fusion, found that aspirin discontinued only 3–7 days before surgery significantly increased the risk of intraoperative bleeding. Alghamdi et al. [4] found similar results in patients undergoing coronary artery bypass grafting. In contrast, the study by Wolf et al. [5] showed that continuation of aspirin up to the day of the surgery did not increase the risk of bleeding, transfusion or other adverse outcomes in patients undergoing pancreatectomy. Similarly, Khudairy et al. [6] assessed the use of clopidogrel and its discontinuation time in hip fracture repair, and found that whether it was stopped ≥1 week or <1 week before surgery did not make any difference to the risk of bleeding or peri-operative complications. Nonetheless, the evidence provided by the present study by Leyh-Bannurah et al. is important, as the risk of bleeding seems to be procedure-specific, depending on the nature and source of potential bleeding (primarily arterial vs primarily venous). The lack of information, however, regarding cardiovascular morbidities in their patient population is an important limitation of their study; as such factors may influence perioperative decision-making, including the threshold for transfusion.

Read the full article

Akshay Sood and Quoc-Dien Trinh*
VUI Center for Outcomes Research, Analytics and Evaluation, Henry Ford Health System, Detroit, MI, and *Division of Urologic Surgery and Center for Surgery and Public Health, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

References

  1. Lamb A. Fast Facts: prostate cancer, seventh edition. BJU Int 2012; 110: E157
  3. Park JH, Ahn Y, Choi BS et al. Antithrombotic effects of aspirin on 1- or 2-level lumbar spinal fusion surgery: a comparison between 2 groups discontinuing aspirin use before and after 7 days prior to surgery. Spine 2013; 38: 1561–1565
  4. Alghamdi AA, Moussa F, Fremes SE. Does the use of preoperative aspirin increase the risk of bleeding in patients undergoing coronary artery bypass grafting surgery? Systematic review and meta-analysis. J Cardiac Surg 2007; 22: 247–256
  5. Wolf AM, Pucci MJ, Gabale SD et al. Safety of perioperative aspirin therapy in pancreatic operations. Surgery 2014; 155: 39–46
  6. Al Khudairy A, Al-Hadeedi O, Sayana MK, Galvin R, Quinlan JF. Withholding clopidogrel for 3 to 6 versus 7 days or more before surgery in hip fracture patients. J Orthop Surg 2013; 21: 146–150
Read more articles of the week

Editorial: Neutrophil-to-lymphocyte ratio as a prognostic factor in upper tract urothelial cancer

/by

The immune system response is critical to cancer development, treatment and progression. Dalpiaz et al. [1]. show that patients with a higher neutrophil-to-lymphocyte ratio (NLR) have a higher cancer-specific and overall mortality when undergoing radical nephroureterectomy for upper tract urothelial cell cancer (UTUC). The study is the first and largest one to evaluate the impact of preoperative NLR on UTUC and proposes its incorporation into our risk assessment tools as an independent predictor of survival.

Pathological prognostic factors such as tumour stage and grade have established importance in UTUC [2]. Additionally, lymphovascular invasion and tumour necrosis have been shown to be independent predictors of survival [3]. Preoperative markers have the advantage of prospective planning and counselling for treatment. The NLR has been studied in various cancers, including renal and gastric, and was recently incorporated into a risk stratification scheme for radical cystectomy patients as an independent prognostic factor for survival [4].

Dalpiaz et al. retrospectively reviewed 202 patients with UTUC who underwent radical nephroureterectomy. A threshold NLR value of 2.7 was used to discriminate between patients. NLR was significantly associated with lymphovascular invasion, but not with age, gender, tumour site, vascular invasion, tumour grade, pathological T-stage, tumour site, tumour location or presence of tumour necrosis. The mean follow-up was 45 months. The median survival was 44.5 months in the low-NLR group and 27 months in the high-NLR group. Multivariate analysis showed that T-stage and NLR were predictors of cancer-specific survival. High NLR and muscle invasion were shown to be independent predictors of overall survival.

Although interesting, these results should be interpreted cautiously as it is very difficult to control all confounders in a retrospective study. The authors did try to address aspects of the inflammatory response by incorporating Eastern Cooperative Oncology Group Performance Status and Charlson Comorbidity Index into their analysis. They found no statistically significant association between NLR and Eastern Cooperative Oncology Group Performance Status or Charlson Comorbidity Index. When adjusting for these variables, the relationships between NLR and cancer-specific survival and between NLR and overall survival were maintained. Although helpful in supporting the conclusions, using the Eastern Cooperative Oncology Group Performance Status and Charlson Comorbidity Index as markers of the inflammatory response should be approached carefully, as many other factors, such as hydronephrosis, tumour invasion, and pre-procedure treatments, which were not evaluated could have a more significant effect on the NLR than general measures of chronic conditions.

The threshold value of the NLR (2.7) was obtained by testing all possible thresholds and choosing a value based on its ability to predict survival and mathematical convenience. Thus the threshold value is self-serving to the conclusion. The statistical analysis suffers due to the dichotomous discrimination as opposed to further divisions like quartiles, but nonetheless shows the value of NLR as an important predictor, the threshold value of which might differ from cohort to cohort.

The present study shows that NLR as an important predictor of survival in UTUC. NLR is easy to perform, relatively inexpensive and is probably already available as part of the standard evaluation of patients with UTUC. It is therefore easy to assess. How should it change our practices? For example, should we be considering neoadjuvant chemotherapy, lymph node dissections or earlier radical surgery in patients with high NLR? The present study develops the hypothesis that can serve as the basis of future validation in a larger cohort or in a prospective fashion.

Read the full article

Moben Mirza
Department of Urology, University of Kansas, Kansas City, KS, USA

References
  2. Rouprêt M, Hupertan V, Seisen T et al.; French National Database on Upper Tract Tumors; Upper Tract Urothelial Carcinoma Collaboration. Prediction of cancer specific survival after radical nephroureterectomy for upper tract urothelial carcinoma: development of an optimized postoperative nomogram using decision curve analysis. J Urol 2013; 189: 1662–1669
  3. Zigeuner R, Shariat SF, Margulis V et al. Tumour necrosis is an indicator of aggressive biology in patients with urothelial carcinoma of the upper urinary tract. Eur Urol 2010; 57: 575
  4. Gondo T, Nakashima J, Ohno Y et al. Prognostic value of neutrophil-to-lymphocyte ratio and establishment of novel preoperative risk stratification model in bladder cancer patients treated with radical cystectomy. Urology 2012; 79: 1085

 

Guideline of Guidelines

/by

Many of us have developed an addiction to sports this summer. The World Cup football in Brazil with its continuous party spirit, the lush green lawns of Wimbledon and then the Test series between India and England. Our Web Editor could not contain himself:

Amidst all the fun and excitement, three important pieces of news are highlighted here:
  1. I requested our Associate Editor Stacy Loeb, who has a strong background in statistical methodology and health services research, to launch a series entitled ‘Guideline of Guidelines’. Most busy urologists tell me that they often find the many different society guidelines confusing. So we decided to publish a critical summary, finishing up with a set of ‘key points’ that our readers can use in their day-to-day practices. And what better way to kick off than with our biggest controversy – screening for prostate cancer [1].
  1. At #BAUS14 we conducted a live audience poll on when (and if) we should go completely digital. Here are the results:
  1. Inflammatory responses to tumours are recognised as being as important as stage and grade in predicting outcomes of treatment. Our ‘Article of the Month’ is a large 12-year European series of radical surgery for upper tract TCC. Neutrophil–lymphocyte ratio appears to be an important biomarker, as values of >2.7 confer worse cancer-specific and overall survivals [2]. The ratio of total neutrophils:total lymphocytes is easy to calculate from a routine preoperative blood test. I hope that many of you will be able to counsel your patients with this clinically useful biomarker.

Prokar Dasgupta
Editor-in-Chief, BJUI
Guy’s Hospital, King’s College London, London, UK

References

Editorial: The importance of knowing testosterone levels in patients with prostate cancer

/by

The paper by San Francisco et al. [1] in this issue of BJUI, reviews 154 patients with prostate cancer who were included in an active surveillance cohort. In all, 54 (35%) progressed to active treatment. Men who had disease reclassification had significantly lower free testosterone than those who were not reclassified. They concluded that on multivariate analysis, free testosterone and a family history of prostate cancer were independent predictors of disease reclassification. The authors acknowledge that this was a retrospective study of small size and the data was missing in some of the men, sex hormone-binding globulin (SHBG), luteinizing hormone and oestradiol were not measured. Nevertheless, this review adds to the increasing evidence that it is important to measure testosterone levels in men with prostate cancer.

Previous studies have indicated that a low testosterone level before treatment for prostate cancer is an independent predictor of a more aggressive high-grade cancer [2]. In addition to this, there appears to be an increased likelihood of extraprostatic disease at the time of diagnosis [3] and an unfavourable response to treatment [4].

Garcia-Cruz et al. [5] in 2012 reported that low testosterone bioavailability is related to a positive prostate cancer diagnosis in patients submitted for prostate biopsy. In a further study, he showed that low testosterone levels were related to poor prognosis factors in men with prostate cancer prior to treatment. Testosterone was inversely related to prostate cancer bilaterally and percentage of tumour in the biopsy. Higher testosterone levels were found in patients allocated to the low-risk progression group. In the multivariate analysis, older age and lower testosterone levels were related to a higher D’Amico risk of progression [5]. The researchers went on to show that higher SHBG and lower bioavailable testosterone are related to prostate cancer detection on biopsy. The study was a prospective analysis of 279 patients referred for prostate biopsy. Low bioavailable testosterone and high SHBG levels were related to a 4.9- and 3.2-fold increased risk of detection of prostate cancer on prostate biopsy taken due to an abnormal PSA result or an abnormal DRE [6].

Free testosterone accounts for about 1–2% of total testosterone and hence most circulating testosterone is bound to SHBG and as such, is inactive. Yamamoto et al. [7] had previously shown that men with a low free testosterone (<1.5 ng/dL) had an increased risk of a high Gleason score (>8) compared with men with higher free testosterone (8% vs 2%; P = 0.04). Additionally, a free testosterone level of <1.5 ng/dL was associated with increased risk of biochemical recurrence of tumour.

Morgentaler et al. [8] have been turning conventional wisdom upside down. They report on 13 symptomatic testosterone deficient men who also had untreated prostate cancer. The men received testosterone therapy while undergoing active surveillance for a median of 2.5 years. None of the men had aggressive or advanced prostate cancer and they were rigorously followed up. Despite effective treatment, neither the PSA level nor prostate volume showed any change. Follow-up biopsies were taken in all of the men at yearly intervals and none developed cancer progression.

It is intriguing to think that the decline in testosterone with age and comorbidities may contribute to tumorigenesis in the prostate. Clearly this study needs to be replicated with much larger numbers. But it seems reasonable to suggest that we ought to know about the hormonal environment existing in our patients with prostate cancer. This will of course, raise the even more controversial area of what to do about men with symptomatic hypogonadism with treated and untreated prostate cancer. There is limited data available on this issue.

Before considering testosterone therapy, the first step should be intensive lifestyle intervention; this is not only known to improve cancer survival, but raises total and free testosterone. Weight loss inhibits aromatase, and other complex cytokines, this reduces the suppression of the pituitary gonadal axis and conversion of testosterone to oestrogen, raising testosterone levels.

Read the full article

Michael Kirby*,†
*The Prostate Centre, London, and †Institute of Diabetes for Older People (IDOP), Beds & Herts Postgraduate Medical School, Puckeridge Bury Campus, Luton, UK

References

  1. San Francisco I, Rojas P, Dewolf W, Morgentaler A. Low free testosterone predicts disease reclassification in men with prostate cancer undergoing active surveillance. BJU Int 2014; 114: 229–235
  2. Massengill JC, Sun L, Moul JW et al. Pretreatment total testosterone level predicts pathological stage in patients with localized prostate cancer treated with radical prostatectomy. J Urol 2003; 169: 1670–1675
  3. Chen SS, Chen KK, Lin AT, Chang YH, Wu HH, Chang LS. The correlation between pretreatment serum hormone levels and treatment outcome for patients with prostatic cancer and bony metastasis. BJU Int 2002; 89: 710–713
  4. Ribeiro M, Ruff P, Falkson G. Low serum testosterone and a younger age predict for a poor outcome in metastatic prostate cancer. Am J Clin Oncol 1997; 20: 605–608
  5. Garcia-Cruz E, Piqueras M, Huguet J et al. Low testosterone levels are related to poor prognosis factors in men with prostate cancer prior to treatment. BJU Int 2012; 110: E541–546
  6. Garcia-Cruz E, Carrión Puig A, Garcia-Larrosa A et al. Higher sex hormone-binding globulin and lower bioavailable testosterone. Scand J Urol 2013; 47: 282–289
  7. Yamamoto S, Yonese J, Kawakame S et al. Preoperative serum testosterone level as an independent predictor of treatment failure following radical prostatectomy. Eur Urol 2007; 52: 696–701
  8. Morgentaler A, Liphultz LI, Bennett R, Sweeney M, Avila D Jr, Khera M. Testosterone therapy in men with untreated prostate cancer. J Urol 2011; 185: 1256–1260
Read more articles of the week

Editorial: Unveiling the surgical risk associated with neoadjuvant chemotherapy in bladder cancer

/by

In this issue of BJU International, Johnson et al. [1] examine the association between neoadjuvant chemotherapy (NAC) for bladder cancer and 30-day morbidity related to radical cystectomy (RC). Level 1 evidence supports use of cisplatin-based NAC for bladder cancer; a meta-analysis of 11 randomised trials including 3005 patients who received NAC found a 5% absolute increase in 5-year overall survival and a 9% absolute increase in 5-year disease-free survival compared with RC alone [2]. Despite this, recent studies have reported underutilisation of NAC at ≈20% [3], with several reasons proposed for this ‘non-compliance’ to guidelines. A 2013 National Cancer Data Base (NCDB) analysis found that increasing age, lower patient income, and treatment at a non-academic institution (P < 0.01) negatively influenced the receipt of NAC, while higher clinical stage and fewer comorbid conditions were associated with higher likelihood of receiving NAC (P < 0.01) [3].

Another relevant concern is that NAC may increase perioperative complications for RC given the toxicities associated with chemotherapy, advanced age and often high rates of renal and cardiac comorbidities among potential candidates [4]. Credit should be given to Millikan et al. [5] for first negating this fear in 2001 with a randomised trial comparing NAC vs adjuvant chemotherapy in patients with bladder cancer; this study did not find any increase in perioperative morbidity.

The present analysis by Johnson et al. [1] further debunks this misconception in contemporary practice (2005–2011), drawing on the American College of Surgeons National Surgical Quality Improvement Program (NSQIP), which prospectively collects a sample of risk-adjusted validated surgical patient data from >450 participating USA hospitals. The authors show that NAC was not an independent predictor of complications, reoperation, wound infection or dehiscence. The robustness of these findings is reinforced by the shorter adjusted length of stay among patients receiving NAC. Given that scant data exists on this topic, the authors contribute a valuable paper that substantially adds to the literature.

Despite its strengths, the study should be interpreted in light of notable limitations that the authors acknowledge. Many crucial variables are not tracked by the NSQIP and therefore cannot be accounted for, including type of chemotherapy regimen, delay between chemotherapy and surgery, surgical technique (open, laparoscopic, robotic), surgical quality (margins, extent of lymphadenectomy), clinical/pathological stage of bladder cancer, and hospital/surgeon volume. Besides, because RC is a morbid procedure with a mean length of stay of 11 days, 30-day complication rates do not capture its true morbidity as well as 90-day rates. In particular, several common complications, such as postoperative ileus or small bowel obstruction, tend to occur later during the postoperative recovery period. As such, chances are that the event rate is biased downward by the short-term duration of data capture by the NSQIP. This study also cannot fully examine the association of NAC with certain subtypes of complications, including gastrointestinal or bleeding complications, especially when other investigators examining robotic RC have reported a conflicting increase in perioperative complications associated with NAC [6] driven by a 27% rate of gastrointestinal complications, which are not tracked by the NSQIP. Of note, unadjusted rates of transfusion and bleeding events were both higher in the NAC group in the present study.

One of the relevant and heartening observations of the report is the gradual increase in the use of NAC over the study period from 4% of eligible patients to 11%, close to the NCDB estimates of 7.6% in 2006 to 20.9% in 2010 (P < 0.01) [3]. Interestingly, there was an increased probability of any complication in the most recent time period (odds ratio 0.47 for 2005–2009 relative to 2010–2011 in the primary multivariate model, P < 0.001). A plausible explanation is that as physicians have heeded the message to increase usage of NAC, treatment has expanded into a wider population with more comorbidities and therefore a greater propensity for complications. It would have been of interest to address this point by restricting the analyses to the most recent data to see if NAC does indeed predict perioperative complications in the most recent period from 2010 to 2011.

Finally, given the lack of detail available in the NSQIP, other relevant questions could not be addressed. Among them it would be relevant to know if complication rates vary between standard MVAC (methotrexate, vinblastine, doxorubicin and cisplatin) and newer chemotherapy regimens such as dose dense MVAC (DD-MVAC) or gemcitabine plus cisplatin (GC). Similarly, the role of the delay or the elapsed time between chemotherapy and surgery on complications might be helpful in future trial planning.

Additional work still needs to be done to identify prognostic factors for both perioperative complications and long-term outcomes after NAC, so that this valuable therapy can be appropriately provided to the correct patients. Indeed, given the lack of randomised controlled trial data investigating less toxic regimens than MVAC, perhaps NAC is underused because clinicians and patients are underserved by the available data. The authors should be commended for their efforts in deconstructing possible barriers to increased uptake of NAC, a therapy known to confer survival benefits for our patients with bladder cancer.

Joaquim Bellmunt,*† Jeffrey J.Leow‡ and William Martin-Doyle§
*Bladder Cancer Center, Dana-Farber/Brigham and Women’s Cancer Center, Boston, MA, USA; †University Hospital Del Mar-IMIM, Barcelona, Spain; ‡Brigham and Women’s Hospital, Division of Urology and Center for Surgery and Public Health, Boston, MA, USA; §University of Massachusetts Medical School, Worcester, MA, USA

Read the full article

References

  1. Johnson DC, Nielsen ME, Matthews J et al. Neoadjuvant chemotherapy for bladder cancer does not increase risk of perioperative morbidity. BJU Int 2014; 114: 221–228
  2. Bellmunt J, Orsola A, Wiegel T et al. Bladder cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. ESMO Guidelines Working Group. Ann Oncol 2011; 22 (Suppl. 6): 45–49
  3. Zaid HB, Patel SG, Stimson CJ et al. Trends in the utilization of neoadjuvant chemotherapy in muscle-invasive bladder cancer: results from the National Cancer Database. Urology 2014; 83: 75–80
  4. Meeks JJ, Bellmunt J, Bochner BH et al. A systematic review of neoadjuvant and adjuvant chemotherapy for muscle-invasive bladder cancer. Eur Urol 2012; 62: 523–533
  5. Millikan R, Dinney C, Swanson D et al. Integrated therapy for locally advanced bladder cancer: final report of a randomized trial of cystectomy plus adjuvant M-VAC versus cystectomy with both preoperative and postoperative M-VAC. J Clin Oncol 2001; 19: 4005–4013
  6. Johar RS, Hayn MH, Stegemann AP et al. Complications after robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium. Eur Urol 2013; 64: 52–57
Read more articles of the week
© 2024 BJU International. All Rights Reserved.