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Editorial: VEIL – is a new standard ready to be accepted?

In this interesting prospective study, Kumar and Sethia [1] provide further evidence that video endoscopic inguinal lymphadenectomy (VEIL) could be considered the procedure of choice for most patients with an indication for ILND. In their comparison with historical patients submitted to open ILND (OILND) in a reference centre in the UK, VEIL achieved reduced morbidity, shorter hospital stay, and equivalent oncological control. Also, we must consider that some cases of the VEIL learning curve were included in this study, suggesting that good results can be obtained with the endoscopic technique from its inception.

The idea for an endoscopic approach to ILND was conceived and developed in a cadaveric model by Bishoff et al. [2] in 2003. In 2005, our group reported the first successful experience in humans [3]. In 2006, in collaboration with the Brazilian National Institute of Cancer, we published a landmark study in the Journal of Urology comparing OILND in one limb and VEIL in the contralateral limb in the same patient to minimise comparative bias [4]. In all, 10 patients with impalpable nodes underwent bilateral ILND. We found that morbidity was reduced with VEIL (20% vs 70%) with the removal of the same number of nodes as with OILND [4]. In 2008, we reported on a series of bilateral VEIL obtaining reduced postoperative morbidity and a mean hospital stay of 1 day [5]. Several other small series have reported essentially the same results that we initially described.

Robot-assisted VEIL duplicates the procedure but is more ergonomic, with excellent freedom of movement and amplification of lymphatic visualisation. Matin et al. [6] reported that robot-assisted VEIL could remove the same number of nodes as the open procedure.

The present study [1] reports a large experience comparing bilateral procedures (VEIL and OILND). The follow-up data for OILND are longer but oncological indicators suggest equivalence. This is also the first report of VEIL after node cytology and dynamic sentinel node biopsy with no related adverse events.

To date, a few series have reported long-term oncological results [1, 7] and future studies will be important to evaluate and reproduce the oncological efficacy of VEIL.

We congratulate Kumar and Sethia [1] for these significant data to establish VEIL in the modern urological armamentarium. Indeed, I really have some doubt as whether a randomised controlled study would be necessary considering the accumulated worldwide data on VEIL in the last 10 years.

This year we present at the University of California meeting the promising results of our Latin America collaborative group with 150 VEIL in 110 patients. The mean (range) follow up was 6 (2–10) years, with an overall morbidity of 30% (Clavien–Dindo grade III–IV, 2%), mean lymph node removal of 8 nodes/groin, node positive disease rate of 25%, inguinal recurrence rate of 2%, cancer-specific survival of 90%, and overall survival of 85% (Tobias-Machado et al., 2016, unpublished data). Our data suggest that we can obtain a dramatic reduction in severe complications and also that VEIL is surviving the test of time.

In my opinion, as the reduction in morbidity is already confirmed, we only need larger series with long-term reports of oncological equivalence with OILND to designate VEIL as a ‘gold standard’ in centres with appropriately trained surgeons.

I speculate that in the near future the utilisation of robotic surgery associated with improvements in imaging methods and contrasts, which will improve the identification of lymph nodes to be removed and lymphatic channels to be clipped, will achieve further reductions in morbidity and optimisation of oncological control.

How to Cite this article:

Tobias-Machado, M. (2017), Video endoscopic inguinal lymphadenectomy (VEIL): is a new standard ready to be accepted?. BJU International, 119: 504–505. doi: 10.1111/bju.13723

Marcos Tobias-Machado
Department of Urology, ABC Medical School, Sao PauloBrazil

 

References

 

 

2 Bishoff JT, Basler JW, Teichman JM et al. Endoscopic subcutaneous modied inguinal lymph node dissection (ESMIL) for squamous cell carcinoma of the penis. J Urol (Suppl.) 2003; 169: 78 (abstract 301)

 

3 Tobias-Machado M, Tavares A, Molina WR Jr, Forseto PH Jr, Juliano RV, Wroclawski ER. Video endoscopic inguinal lymphadenectomy (VEIL): minimally invasive resection of inguinal lymph nodes. Int Braz Urol 2006; 32: 31621

 

4 Tobias-Machado M, Tavares A, Ornellas AA, Molina WR Jr, Juliano RVWroclawski ER. Video endoscopic inguinal lymphadenectomy: a new minimally invasive procedure for radical management of inguinal nodes in

 

 

 

7 SchwentneC, Todenhofer T, Seibold J e t al. Endoscopic inguinofemoral lymphadenectomy extended follow-up. JEndouro20 13; 27: 497503

 

Editorial: Is minimally invasive inguinal node dissection the way forward?

In this issue of BJUI, Kumar and Sethia report their experience of laparoscopic inguinal node dissection for patients with penile cancer [1]. The authors should be congratulated for what is a technically and feasibly difficult study to complete.

The step-wise spread of penile carcinoma first to the inguinal lymph nodes is well known. It is also recognized that accurate staging and treatment of inguinal metastases play a crucial part in a patient’s management pathway. Furthermore, evidence points to a survival advantage for those who undergo prophylactic inguinal lymph node dissection (ILND) and have positive nodes, compared with those treated with surveillance and delayed dissection when nodes become palpable or radiologically positive.

The overall postoperative complication rate after ILND has been reported to be nearly 50% or even up to 75%. Patients with comorbidities or locally advanced disease are at particular risk of postoperative morbidity [2]. High rates of wound dehiscence and skin necrosis after ILND have also been reported [3]. More recently, complication rates among men with no palpable adenopathy have been reported to be decreasing in comparison with historical experience, but overall complication rates still range from 10 to 40%.

Adoption of dynamic sentinel node biopsy has reduced the absolute number of prophylactic ILNDs, but in any high-volume unit (as is the case in the UK supra-network centres), a large number of inguinal node dissections will still be undertaken [4].

For these reasons it is desirable to minimize or modify the inguinal wound to reduce the complication rate, and the use of minimally invasive techniques has gradually progressed over the last 10 years.

The first case series reporting the use of laparoscopic node dissection (videoendoscopic inguinal node dissection [VEILND]) described 10 patients who underwent bilateral ILND using standard lymphadenectomy on one side and the VEILND technique on the contralateral side [5]. A more recent development has been the incorporation of robotic assistance as an enabling tool for performing ILND [6].

In these small series the technique appeared to be safe and oncologically comparable to open surgery, but the numbers were too small to give a meaningful assessment of complications. It is therefore welcome to read a paper on a high-volume unit’s experience of VEILND.

The authors describe their experience of VEILND on a sequential prospective group of patients and compared them with a historical control cohort who underwent open inguinal node dissection. The data appear to show a significant difference in length of stay and wound-related comorbidity in favour of the minimally invasive approach without compromising oncological outcome. Interestingly, the rate of lower limb lymphedema was also significantly reduced in the VEILND group.

The headline data are impressive but the comparison does have a number of potential weaknesses. Firstly, the rate of wound-related complications is quite high in the open group, with 23% of patients needing re-exploration or debridement and 37% some form of drainage of collection. The choice of incision position, length and preparation of skin flaps can influence the rate of wound breakdown and length of stay.

Secondly, the headline 6% complication rate for VEILND does not include the 27% lymphocoele rate which is still a troublesome complication in both the open and endoscopic groups.

Finally, there is no mention of the limitations of the technique with size and extent of the malignant node burden. The paper states that all patients were included, and yet in any high-volume centre there must be patients with grossly enlarged and sometimes fungating or fixed nodes and I would have thought that VEILND would not be appropriate in these instances.

In conclusion, there is much to commend this paper and the direction of travel may well be towards minimally invasive techniques; however, as with all comparisons between open and keyhole surgery, the focus should be on improving the open technique to its limit. Only then will the results be meaningful and adopted with confidence.

How to Cite this article:

Watkin, N. (2017), Is minimally invasive inguinal node dissection the way forward?. BJU International, 119: 505–506. doi: 10.1111/bju.13761

Nick Watkin
Department of Urology, St Geo rges Hospital, London, UK

 

References

 

 

April Editorial: The BJUI’s clinical trials initiative

The BJUI supports clinical trials. Plain, simple, and with some new strategies.

Randomised clinical trials (RCTs) are the highest level of evidence-based medicine. We know this to be true, but we also know that RCTs are a challenge to fund, accrue patients, execute, and follow to endpoints. From a statistician’s point of view, RCTs provide unbiased estimates of the effects of different treatments. From a clinician’s point of view, RCTs provide the grandest of experiments in nature – a true test of option A vs option B. We are thrilled when one option beats the other. We can be satisfied if the options are equivalent, at least knowing the matter is settled and move on to the next question. Either way, the story lines can be rich with ongoing debate, drama, and analysis: were the cohorts truly equivalent? Was the study population generalisable? Were the treatments contemporary? Were there unintended harms/toxicities?

Allow us to illustrate some examples of what we propose to our readers. In 2003, Thompson et al. [1] published the famous Prostate Cancer Prevention Trial in the New England Journal of Medicine: ‘The influence of finasteride on the development of prostate cancer’. This landmark study has been cited 2541 times, according to Google Scholar. Looking further at impact, one can go to the www.swog.org site and query the protocol ‘SWOG-9217’ and see that over 150 publications have been produced using this dataset (16 in 2016!). Several publications pre-dated the primary endpoint paper and discussed trial design, the dilemma of chemoprevention, and updates to trial progress. Post primary endpoint, publications have looked at multiple strategies – costs, the high-grade findings, longer-term follow-up, biopsy findings from the placebo arm, etc. Just last year, the UK made its mark on the prostate cancer world with the landmark Prostate Testing for Cancer and Treatment (ProtecT) study [2]. Again, we see the primary endpoint paper in the New England Journal of Medicine, but secondary endpoint papers, such as the quality-of-life outcomes are in the BJUI [3], and a mortality outcome analysis for trial screen failures in European Urology [4].

The BJUI can support clinical trial efforts through multiple pathways. Certainly, we would love to receive a primary endpoint paper from an important RCT in urology. We can also have impact by featuring important secondary endpoint papers, trial design papers (preferably ones that read like a good review article, with the trial proposed as the ‘answer’ to the dilemma), as well as smaller/early phase I–II trials that are stand-alone pieces of key knowledge. Figure 1 shows a possible flow chart of a RCT with each box representing possible publication points. In addition to content in the BJUI, our webpage Blogs section has a ‘rapid response team’ to start immediate dialogue on important RCTs published in other journals. For example with the recent Yaxley et al. [5] trial in the Lancet, our blogs section, led by Declan Murphy, had over 10 000 views and over 50 follow-up comments. So clearly, our readers care about RCTs.

apr-ed

Figure 1. A possible flow chart of a randomised clinical trial (RCT) with each box representing possible publication points. QOL, quality of life; f/u, follow-up.

Finally, the BJUI can help with RCTs in two more ways. For the reader, we will highlight RCT-related papers in their native sections (i.e. oncology, functional, education) with a special ‘Trials’ headline, and will invite experts to comment on the significance of the study. For reviewers and authors, we will be critical on RCT design, such that flaws are identified, and papers not given inflated significance. It is frustrating to receive papers that lack adequate reporting on what researchers did, RCT-related papers submitted to the BJUI frequently fail to adhere to the 2010 Consolidated Standards of Reporting Trials (CONSORT) guidance for reporting RCTs, which potentially leads to major revisions, if not outright rejection. The CONSORT requirements are on our author submission guidelines, but ideally these are read and adhered to in advance, as many are not possible to correct after the fact. Recently, we have also added that all RCTs must be registered (i.e. clinicaltrials.gov or similar) before the first patient is enrolled.

John W. Davis, Associate Editor, Urological Oncology* and
Graeme MacLennan, Consulting Editor, Statistics and Trials

*MD Anderson Cancer Center, Houston, TX, USA and University of Aberdeen, Aberdeen, UK


References

How to Cite this article

Davis, J. W. and MacLennan, G. (2017), The BJUI‘s clinical trials initiative. BJU International, 119: 503. doi: 10.1111/bju.13837

 

Editorial: An end to the phenomenon of ‘upgrading’ in early prostate cancer?

The phenomenon of ‘upgrading’ in early prostate cancer is one of those unusual events that is both useful to us on the one hand and undesirable on the other; useful because the phenomenon gifts us a direct measure of the precision of our risk stratification methods for men recently diagnosed, and undesirable because the perfect pathway should, ideally, be free of any upgrading.

Upgrading occurs in a number of settings. We see it at play to some degree when an unreliable test is re-applied in the same subject. The REDUCE study [1] showed us that just under one fifth of men will convert from a status of ‘cancer-free’ to one of ‘cancer-present’ as a result of a second exposure to the same test; that is, TRUS-guided biopsy. We see it in full play when an unreliable test is followed by a more accurate test. Shaw et al. [2] have reminded us once again – as have a number of others – of our limited ability to risk-stratify patients with early prostate cancer. They reported a 50% upgrading when they compared the results of TRUS biopsy against the final pathology at radical prostatectomy. In other words, half the patients went on to their definitive therapy with an incorrect grade attribution [2].

It would be a great pity if, in the modern era, the only route available to patients who wanted to be sure of their risk status was to agree to surgical removal of the prostate. Surely, the value of accurate risk stratification is derived from using it to allocate appropriate and effective care. Risk stratification needs to be linked to or closely follow diagnosis if it is to be put to work for patients.

Nowhere is this need greater than in men whose treatment preference is tissue preservation. The study, in this issue of BJUI, by Pessoa et al. [3] adds to our knowledge on the subject and equips us with a strategy to mitigate some of the errors that are inherent to the standard diagnostic pathway.

In the present study, the authors evaluated the role of a single exposure to MRI (and the opportunity that resulted to undertake a targeted biopsy of an MRI-derived abnormality as well as systematic sampling) in 105 men who had been attributed a diagnosis of low-risk prostate cancer – and, as a result, were deemed to be suitable for active surveillance. The authors used prostate imaging reporting and data system (PIRADS) scoring to interpret and communicate MRI risk. In summary, men attributed a low PIRADS score (PIRADS 1–3) had a low probability of being re-classified to a higher risk. In contrast, men attributed PIRADS score 4 or 5 had a probability of 70–100% of being re-classified. The authors calculated a sensitivity of 93% for MRI to predict ‘re-classification’. This equates to a 93% sensitivity to predict the presence of clinically significant disease as re-classification occurred when there was a transition from low-risk to higher-risk disease.

These results concur with those of others who are working in this area [4] and are in line with current recommendations [5]. One observation that is worth highlighting – because it is a current controversy in the field – relates to the utility of the systematic (or semi-random) biopsies as a component of the confirmatory biopsy. Whilst targeted biopsy was superior to systematic biopsy at identifying clinically significant disease, omission of the systematic biopsies would have resulted in five significant cancers being overlooked. The less perfect the targeted biopsy, the greater the reliance on the systematic. In the present study, the lesion generation and the targeting may have been compromised by one or two issues. Using TRUS biopsy as the authors did (as opposed to transperineal biopsy) to access all areas of the prostate is always going to be a challenge. To do so without image registration makes it even harder. To use PIRADS – as opposed to a Likert scale – as a method of interpreting and communicating MRI outputs will, very likely, lead to an under-reporting of the smaller, high-grade lesions [6]. This is because PIRADS 2.0 is triggered by a volume threshold towards the upper end of the scale. Such lesions might be more prevalent in an apparently ‘low-risk’ population such as the one under scrutiny. If this is the case, they will not be identified as ‘targets’ by virtue of a high PIRADS score. As a consequence they cannot be identified by targeting but might be picked up by the random fall of the needles.

Mark Emberton
Division of Surgery and Interventional Science, University College London, London, UK
Read the full article
References

1 Andriole GL, Bostwick DG, Brawley OW et al. Rittmaster RS; REDUCE Study Group. Effect of dutasteride on the risk of prostate cancer. N Engl Med 2010; 362: 1192202

 

2 Shaw GL, Thomas BC, Dawson SN et al. Identication of pathologically insignicant prostate cancer is not accurate in unscreened men. Br Cancer 2014; 110: 240511

 

4 Nassiri N, Margolis DJ, Natarajan S et al. Targeted biopsy to detect Gleason score upgrading during active surveillance for men with low- vs. intermediate-risk prostate cancer. J Urol 2016; [Epub ahead of print]. doi: 10.1016/j.juro.2016.09.070.

 

5 Moore CM, Giganti F, Albertsen P et al. Reporting magnetic resonance imaging in men on active surveillance for prostate cancer: the PRECISE recommendations-a report of a European school of oncology task force. Eur Urol 2016; [Epub ahead of print]. doi: 10.1016/j.eururo.2016.06.011.

 

 

Editorial: Nephrometry scoring systems: valuable research tools, but can they be applied in daily clinical practice?

In this issue of BJUI Schiavina et al. [1] report on the RENAL and PADUA nephrometry scoring systems in predicting peri-operative outcomes, including warm ischaemia time and postoperative complications, in a multi-institutional cohort of patients undergoing robot-assisted partial nephrectomy. The authors showed that tumours classified as being of intermediate and high complexity on the PADUA score and high complexity on the RENAL score were associated with a nearly threefold higher risk of longer warm ischaemia times (>20 min). In addition, more complex tumours carried a higher risk of grade 3–4 postoperative complications (most commonly bleeding requiring angioembolization and urine leak requiring a ureteric stent). Notably, the two scoring systems were found to be similar predictors of these peri-operative outcomes on receiver-operating curve (ROC) analyses [1].

This represents the first large, multicentre study to evaluate the accuracy of these scoring systems in a cohort of patients who purely underwent robot-assisted surgery. A recent study by Borgmann et al. [2] found that, among the reported scoring systems, the RENAL nephrometry score correlated best with achieving negative surgical margins, shorter ischaemia times, and low postoperative complication rates; however, only 9% of patients underwent robot-assisted surgery. Another contemporary series showed concordance between the RENAL and PADUA scoring systems in predicting ischaemia times and complication rates, albeit in patients who only underwent open surgery [3].

Current guidelines recognize nephron-sparing approaches to small renal masses as the standard of care in well-selected patients, with the robot-assisted platform being predominantly adopted in clinical practice where available. Certainly, these nephrometry scores are valuable for urologists in counselling patients on the potential risk of complications specific to the surgical anatomy of the tumour. In addition, the RENAL and PADUA scores (and others) provide a quantitative, objective method for comparing data from different studies and different institutions.

As nephrometry scoring systems continue to be critically evaluated in the robotic surgery era, the question that naturally arises is: which system is best? With regard to this question, the data in the present study do not necessarily favour one or the other for the prediction of clinically relevant peri-operative outcomes. One must recognize, however, that several other anatomy-based scoring systems exist and were not examined in this manuscript [4-6]. While these are very valuable research and patient counselling tools, one must caution against using these nephrometry tools to make clinical decisions; for example, attempting to predict benign vs malignant histology (without a biopsy), attempting to predict high vs low grade tumours, or deciding on whether to perform a radical vs partial nephrectomy, or an open vs minimally invasive approach. After all, one must keep in mind that the area under the curve for these tools is in the range of 0.58–0.63 (0.50 being equivalent to toss of a coin).

It would have been interesting to include clinical size only in the present multivariate analysis (as was done for RENAL and PADUA scoring) and ROC analysis to compare this simple variable with the studied nephrometry scores. Future research should examine additional confounders that could potentially affect postoperative complication rates, such as BMI, adherent perinephric fat, experience of the surgeon actually performing the partial nephrectomy, technique of resection used (e.g. enucleation or resection) among others. This may help to distinguish a single system as the optimum model for use in research and in patient counselling regarding potential postoperative complications.

Matthew A. Meissner and Jose A. Karam

 

Department of Urology, University of Texas MD Andersonn Cancer Center, Houston, TX, USA

 

Read the full article

 

References

 

 

 

3 Kriegmair MC, Mandel P, Moses A et al. Dening Renal Masses: comprehensive Comparison of RENAL, PADUA, NePhRO, and C-Index Score. Clin Genitourin Cancer 2016; [Epub ahead of print]. doi: 10.1016/ j.clgc.2016.07.029.

 

 

5 Hakky TS, Baumgarten AS, Allen B, Lin HY, Ercole CE, Sexton WJSpiess PE et al. Zonal NePhRO scoring system: a superior renal tumor complexity classication model. Clin Genitourin Cancer 2014; 12: e138

 

6 Simmons MN, Ching CB, Samplaski MK, Park CH, Gill IS et al. Kidney tumor location measurement using the C index method. J Urol 2010; 183: 170813

 

Editorial: Ultrasonography vs computed tomography for stone size

In this edition of the BJUI Ganesan et al. [1] report a retrospective analysis of 552 ultrasonography (US) examinations that were followed by a non-contrast CT within 60 days in 486 patients collected over an 18-year period (1995–2012). The sensitivity of US for stone detection was 54% and its specificity was 91% when compared to CT, and sensitivity was positively associated with stone size (increasing from 73% for stones of 0–4 mm to 77% for 5–10 mm, and 89% for >10 mm; P < 0.001), but not with intra-renal location of stones (P = 0.58). US overestimated the size of stones that were <10 mm (P < 0.001), and had a tendency to underestimate size for those >10 mm (P = 0.05).

Stones were grouped into three size categories, based on clinical relevance to stone management: ≤4 mm (where observation would likely be recommended), 5–10 mm (where shockwave lithotripsy [SWL] would be chosen) or >10 mm where an endoscopic approach would be undertaken). Using these thresholds, 39% of cases would have been misassigned to observation and 14% of patients would have been inappropriately advised to undergo active treatment.

One may question the use of CT as the ‘gold standard’, as CT is also prone to sizing inaccuracy. Nevertheless, the headline findings that the inaccuracies inherent in US diagnosis and sizing may compromise clinical management are important. Other authors have made similar observations: in a literature review, Ray et al. [2] reported that US sensitivity was 45% for the detection of renal and ureteric calculi, with specificity up to 94% for ureteric stones and 88% for renal stones and that US overestimated stone size by a mean of 1.9 mm over CT, especially with stones of <5 mm. Similarly, Sternberg et al. [3] showed that the largest stone diameter was over-estimated by an average of 2.2 mm with US, and that errors increased with reducing stone size, rising from a 3% difference in stones >10 mm to 27% for those of 5–10 mm, and an 85% difference in stones ≤5 mm.

It is well established that, whilst having the advantage of no radiation dose, that US is a ‘user dependent’ study but there are also inherent limitations of US compared to CT for stone imaging. CT is capable of much finer spatial resolution, whilst US is prey to more diagnostic confounders. Reflectivity arising from sinus fat or the edges of the papillae may be mistaken for small calculi. For size, it can be difficult to delineate stone edges with the same precision as with CT. The sensitivity of US for stone detection can be improved by adjusting the imaging modalities between ray line (the conventional form of US), spatial compound and harmonic imaging (the most accurate stone size modality). Techniques such as increasing the gain and the transducer-to-stone depth and identifying ‘twinkle artefact’ using colour Doppler have also been used to improve stone detection [4].

However, manoeuvres to improve sensitivity of US may also compromise size measurement. An in vitro study has shown that each 2 cm increase in depth setting increases the size overestimation of stones by ~22% [5]. Using calcium oxalate monohydrate stones, the same group have shown that measuring the posterior acoustic shadow provided a more precise assessment of stone size than measurement of the stone itself [4]. Interestingly, the accuracy of stone width measurement was worse with greater transducer-to-stone depth, but measurement of the shadow width was independent of depth, and all US modalities (ray line, spatial compound, and harmonic imaging) performed similarly for shadow size. Shadow measurement was accurate to within 1 mm of the stone size [4], and similar findings have been shown in vivo, where 73% of the stone measurements and 85% of the shadow measurements were within 2 mm of the size on CT [6].

Unfortunately, not all stones cast an acoustic shadow, particularly the smaller ones, which are most likely to be over-sized. May et al. [6] showed that 89% of stones >5 mm, but only 53% of stones <5 mm demonstrated a posterior acoustic shadow. However, this may provide a further value for US-based clinical decision making, as stones that do not shadow are most likely <5 mm and are small enough to pass spontaneously, and therefore to be managed conservatively.

It is also important to be aware that CT stone measurements are also prone to error and inter-observer variability. Comparing in vitro CT measurements of stones in a ‘kidney sized potato model’, Eisner et al. [7] have shown that the most accurate measurements were obtained using magnified ‘bone window’ settings, which showed a mean 0.13 mm difference compared to a ‘gold standard’ measurement using callipers. This study also included a comparison of size estimate for spontaneously passed ureteric stones (thus a true reference standard) demonstrating that magnified ‘bone window’ measurements were equivalent to digital calliper measurements (the mean underestimation vs digital callipers was only 0.3 mm, P = 0.4), while measurements using magnified soft tissue windows were statistically different (mean underestimation 1.4 mm, P = 0.001) [7].

With its safety and accessibility, US should be the ideal modality for postoperative follow-up, both for assessment of stone recurrence, monitoring for enlargement of residual fragments, and for identifying the rare but important finding of ‘silent obstruction’, with the potential to lose renal function. However, given the ‘real-life’ data reported in this edition of the BJUI [1], and particularly the findings that 22% of patients might have been managed inappropriately when using US for decision making alone, increasing to 43% of patients who had stones between 5 and 10 mm on US, the authors have concluded that patients monitored by US might benefit from an additional CT if intervention is being considered, particularly for stones in the 5–10 mm range by US measurement.

Given the key importance of stone size to the outcome of interventions for stone disease, accurate imaging should translate into improved decision making and patient counselling and allow fairer inter-surgeon and departmental comparisons. Until the best US protocol and settings have been established, we recommend that, when US is used for diagnosis or follow-up, careful optimisation of the settings is crucial. Colour Doppler for ‘twinkle artefact’, and a high gain setting can be used to reduce the risk of missing stones, combined with removing all filtering and compressing the grey scale range to enhance the posterior shadowing. Harmonic imaging (which is now available on most commercial machines) is more accurate than cross beam or compound beams (that are used for standard renal US settings). When decisions need to be made, particularly those based on stone size, CT of the kidneys, ureters and bladder remains invaluable, from which the longest stone diameter should be measured, using magnified images and the ‘bone window’ setting. Current methods for accurate estimation of stone volume are impractical or imprecise. Manual segmentation can be accurate but is laborious, whilst standard semi-ellipsoid formulae cannot account for the wide variety of stone shapes seen in practice. Further studies devoted to simplifying stone volume estimation are necessary. There is also the wider challenge of how best to report stone imaging data. The key variables are stone size, density and location; and the morphology of the collecting system. Agreement between the various stakeholders – sonographers, radiologists and endourologists – over imaging standards and a minimal data set for stone imaging would improve management.

Daron Smith* and Uday Patel

 

*Institute of Urology, University College Hospital, and Department of Radiology, St Georges Hospital, London, UK
Read the full article

 

References

 

 

2 Ray AA, Ghiculete D, Pace KT, Honey RJ. Limitations to ultrasound in the detection and measurement of urinary tract calculi. Urology 2010; 76: 295300

 

3 Sternberg KM, Eisner B, Larson T, Hernandez N, Han J, Pais VMUltrasonography signicantly overestimates stone size when compared to low-dose, noncontrast computed tomography. Urology 2016; 95: 6771

 

4 Dunmire B, Harper JD, Cunitz BW et al. Use of the acoustic shadow width to determine kidney stone size with ultrasound. J Urol 2016; 195: 1717

 

5 Dunmire B, Lee FC, Hsi RS et al. Tools to improve the accuracy of kidney stone sizing with ultrasound. J Endourol 2015; 29: 14752

 

6 May PC, Haider Y, Dunmire B et al. Stone-mode ultrasound for determining renal stone size. J Endourol 2016; 30: 95862

 

 

Editorial: Laparoscopic renal mass cryoablation: an operation in search of an indication

In this issue of BJUI, Nielsen et al. [1] report the oncological and surgical outcomes from a multi-institutional cohort of patients receiving laparoscopic cryoablation (LCA) as primary therapy for solitary renal masses <4 cm in size (cT1a). This work represents the latest addition to a growing body of literature in an important oncological space that lacks prospective/randomized evidence to guide practitioners counselling patients with kidney cancer. Although the article does not advance the discussion toward higher levels of evidence, the results are nonetheless provocative and several strengths and weaknesses deserve comment.

While nephron-sparing surgery has become the recognized standard of care for cT1a renal lesions [2, 3], the reality remains that certain patients carry unacceptable risk profiles for partial nephrectomy, making less invasive options preferable. Such indications might include being elderly or frail, having hereditary kidney cancer syndromes prone to metachronous renal tumours, or having a solitary kidney. For such patients, focal renal mass ablative techniques have emerged as a safe alternative to extirpation that avoids the permanent nephron loss associated with radical nephrectomy. From an oncological perspective, however, cryotherapy, radiofrequency ablation and microwave ablation (by any approach) all have yet to be studied against partial nephrectomy in a prospective fashion. Numerous retrospective analyses have attempted to fill the void [4], yet the general consensus among most academic kidney surgeons is that renal mass ablation offers acceptable but inferior cancer control compared with surgery [5].

In this retrospective analysis by Nielsen et al., 808 patients underwent LCA between 2005 and 2015, 514 (63.4%) of whom had pre-procedural biopsy-proven RCC. The principal findings described in the present study include not only 5- and 10-year disease-free and overall survival, but also morbidity and mortality outcomes after LCA. The authors should be commended for the structure of their design, which included a high proportion of patients with available preoperative biopsy data. Additionally, clear definitions of treatment success, ‘residual unablated tumour’ and ‘local tumour progression’ are provided, and consistent follow-up imaging protocols were employed by the institutions involved. In each of these ways, Nielsen et al. overcome many of the pitfalls that have clouded the interpretation of results from previous reports.

Nevertheless, the oncological outcomes reported in this study, which are on a par with those for partial nephrectomy as well as other ablative techniques, must be approached with a degree of skepticism. As there is no alternative treatment cohort included in the study, omission of anatomical complexity data (in the form of nephrometry scoring) prohibits any meaningful comparison with patients having undergone ablative procedures or partial nephrectomy from other series. Availability of these data is essential for the reader to gauge the influence of selection bias in the interpretation of the results.

From a morbidity and mortality standpoint, the reported 16% overall complication rate, 3% rate of severe complications (defined as Clavien III–V) and three deaths within 30 days of the procedure might have been strengthened by the missing nephrometry data, as the rate of complications would be expected to increase with the complexity of the renal mass [6]. Also noticeably absent from the analysis are granular comorbidity and previous surgery data, both of which intuitively predispose patients to complications when undergoing minimally invasive surgery.

With these limitations in mind, the experienced kidney surgeon is not likely to see LCA as an equally effective or safer alternative to minimally invasive partial nephrectomy, which can be performed with similar complication rates and length of hospital stay without sacrificing oncological efficacy in most patients. Similarly, the question of why the practitioner should assume the risks of LCA when percutaneous cryoablation is readily available at many contemporary kidney cancer centres is unanswered by the present study. Indeed, with increasingly complex renal masses being managed via minimally invasive nephron-sparing surgery, and active surveillance of small renal masses gaining traction in the appropriate patient population, cryoablation via a laparoscopic approach unfortunately may represent another urological application without a well-defined indication going forward. We hope that the results presented by Nielsen et al. in this issue of BJUI encourage investigators to enroll patients in prospective trials aimed at comparing available ablative techniques or partial nephrectomy in matched cohorts to identify the ideal patient population for this operation and further clarify the oncological and clinical outcomes compared with surgical excision.

Daniel C. Parker and Brian W. Cross

 

Department of Urologic Oncology, University of Oklahoma Stephenson Cancer Center, Oklahoma City, OK, USA

 

Read the full article

 

References

 

1 NielsenT, Lagerveld B, Keeley F et al. Oncologic outcomes and complication rates after laparoscopic-assisted cryoablation: a EuRECA multi-institutional study. BJU Int 2016. [Epub ahead of print].

 

2 Campbell SC, Novick AC, Belldegrun A et al. Guideline for management of the clinical T1 renal mass. J Urol 2009; 182: 12719

 

3 Ljungberg B, Bensalah K, Caneld S et al. EAU guidelines on renal cell carcinoma: 2014 update. Eur Urol 2015; 67: 91324

 

4 Wagstaff P, Ingels A, Zondervan P et al. Thermal ablation in renal cell carcinoma management: a comprehensive review. Curr Opin Urol 2014; 24: 47482

 

5 Kutikov A, Smaldone MC, Uzzo RG. Focal therapy for treatment of the small renal mass: dealers choice or a therapeutic gamble? Eur Urol 2015; 67: 2601

 

 

Editorial: Rethinking cancer surveillance with shared-care models and survivorship plans: the time is now!

Urologists are increasingly facing significant practice concerns related to timely access, surgeon availability, clinical throughput and rising cost of care, yet little has changed over the years regarding the routine postoperative surveillance of urological cancers. While urologists have appropriately focused evaluations on oncological outcomes and procedure-specific quality-of-life concerns, the ability to maintain this practice model in the setting of more new patients (and subsequently more cancer survivors) seems unrealistic. In addition, gaps exist with the current model related to timely and effective communication to the local care team and assurances that specialists comprehensively address all concerns raised by patients. Furthermore, the role of the local care team in cancer survivorship remains poorly defined. Recognising these and other unmet needs in cancer care survivorship, the American Cancer Society (ACS) and the American Society of Clinical Oncology (ASCO) recently published guidelines on cancer survivorship [1-3]. The guidelines recommend a standardised approach to follow-up with emphasis on quality, comprehensive patient assessments, value, and shared use of a multidisciplinary team. With prostate cancer survivorship, for instance, ASCO recommends PSA checks every 6–12 months for the first 5 years and then annually (higher-risk patients can have more frequent checks), adherence to ACS guidelines for early detection of prostate cancer, assessment of physical and psychological effects of prostate cancer and it’s treatments, and annual assessments for long-term or late side-effects [3]. To help with the coordination of care between the patient, the oncological specialist, and the local primary care provider, survivorship care plans have been developed. [4]. While use of survivorship care plans has been sparse in urology to date, new mandates will spur their use in the coming years and development will likely involve innovative healthcare delivery solutions.

Leading the way in this nascent field, Emery et al. [4] report, in this issue of BJUI, an innovative phase II prospective randomised study on the feasibility of a novel shared-care model for follow-up of patients with prostate cancer. Men who had completed treatment for low- and moderate-risk prostate cancer were randomised to undergo usual care or shared care with the assistance of the patient’s primary care team. The novel shared-care model substituted two postoperative urology visits with three postoperative visits in primary care, provided patients and primary care providers a survivorship care plan, included appointment reminders, and provided a novel mechanism to screen for distress and other unmet needs. Among the 88 men randomised in the prospective study, no significant differences were noted between delivery models for satisfaction of care, overall quality of life, incidence of distress, or compliance with serum PSA testing. Patients in the shared-care model were significantly more likely to prefer the new model compared to normal care (cases, 63% vs controls, 24%, P < 0.001). Importantly, the shared-care model was also more economical, saving 323 Australian dollars compared to usual care [4].

The authors should be congratulated for their well-designed study and early contribution to the field. Rethinking all aspects of care delivery will become increasingly important as the practice of urology responds to access limitations, the shortage of urologists, and financial pressures of value-based reimbursement. The report also engenders many questions about the ideal care model of the future, composition of the collaborative care team, and the importance of making evidence-based clinical recommendations. For instance, are already overburdened primary care providers ideal or realistic in shared-care models? Should care remain primarily under the control of urologist with assistance provided by other current (e.g. advance practice providers, urology nurses) or future team member roles (e.g. survivorship care coordinators)? What role can the patient alone play in a self-guided survivorship care plan under the watchful eye of the collaborative care team acting asynchronously? How can enabling technologies such as smartphones, mobile applications, wearables, and video-conferencing contribute to high-value cancer surveillance building upon the principles highlighted in the current article and further engaging patients in their cancer survivorship care? [5]. Lastly, what actually are the evidence-based imperatives of survivorship care (what risk groups, what testing intervals and duration of testing) that provide measurable value to the patient experience? In the current study [4], for instance, high risk patients were excluded but ultimately these patients may be best suited for comprehensive survivorship care. Future work on survivorship and care models will hopefully continue to advance ‘win-win’ situations where patients and providers alike experience increasingly high-value systems of healthcare delivery.

Read the full article
Matthew T. Gettman

 

Mayo Clinic Department of Urology, 200 First Street, SW, Rochester, MN 55905, USA

 

References

 

1 Mayer DK, Nekhlyudov L, Snyder CF, Merrill JK , Wollins DS, Shulman LN. American Society of Clinical Oncology clinical expert statement on cancer survivorship care planning. J Oncol Pract 2014; 10: 34551

 

2 Skolarus TA, Wolf AM, Erb NL et al. American Cancer Society prostate cancer survivorship care guidelines. CA Cancer J Clin 2014; 64: 22549

 

 

 

 

February Editorial: Raising the bar for systematic reviews with Assessment of Multiple Systematic Reviews (AMSTAR)

The BJUI has a longstanding track record in promoting the dissemination of high-quality unbiased evidence and helping their readership to understand why the principles of evidence-based medicine matter. This devotion is witnessed by the work that goes into every issue of the journal, as well as past initiatives such as providing a level of evidence rating for clinical research articles or publishing educational articles such as the ‘Evidence-Based Urology in Practice’ series [1, 2].

Major foci for clinically oriented specialty journals are systematic reviews and meta-analyses. Systematic reviews have a preeminent role in guiding the practice of evidence medicine by addressing focused clinical questions in a systematic, transparent and reproducible manner. Defining criteria of a high-quality systematic review include: an a priori registered protocol, a comprehensive search of multiple sources including unpublished studies (to avoid publication bias), an assessment of the quality of evidence that goes beyond study design alone, and a thoughtful interpretation of the findings. Systematic reviews inform clinicians and patients at the point of care, form the foundation of evidence-based clinical practice guidelines, and help shape health policy [3]. They also find frequent citation and can raise a journal’s impact factor. There is therefore more than one good reason for journals to care about the quality of systematic reviews.

Meanwhile, a study in this issue of the BJUI [4] shows that the methodological quality of systematic reviews published in the urological literature is modest, varies substantially, and has failed to improve over time. This contrasts to randomised controlled trials’ reporting quality that appears to have improved substantially over time, probably due to increased awareness among clinical researchers, urology readers and journal reviewers [4, 5]. The study [4] used the Assessment of Multiple Systematic Reviews (AMSTAR), a validated 11-item instrument, to measure the methodological quality of systematic reviews with higher scores reflecting better quality.

The authors [4] surveyed four major urological journals and compared the periods 2013–2015 to 2009–2012 and 1998–2008. Despite a dramatic increase in the number of systematic reviews published each year, methodological quality has stagnated with mean AMSTAR scores ± standard deviations of 4.8 ± 2.4 (2013–2015; = 125), 5.4 ± 2.3 (2009–2012; = 113) and 4.8 ± 2.0 (1998–2008; = 57). The average systematic review therefore has deficits in over half the 11 AMSTAR criteria and is of only modest quality thereby undermining our confidence in their results. Although the mean AMSTAR score of 5.6 ± 2.9 for 25 systematic reviews published in the BJUI in 2013–2015 compared favourably to similar studies in other leading urology journals, the difference was not statistically significant.

What are we going to do about it? Inspired by these findings, the BJUI is launching a new initiative to raise awareness for the issue of methodological quality of systematic reviews among its readership and raise the bars for its contributors. Future systematic review authors will be asked to submit an AMSTAR-based checklist to provide enhanced transparency about its methods that will be reviewed as part of the editorial review process. These include documentation of an a priori written protocol and ideally, registration of the systematic review through the Cochrane Collaboration or the Prospective Register of Systematic Reviews (PROSPERO). Such a protocol should outline all important steps of the review process including the definition of outcomes, study inclusion and exclusion criteria, details about the literature search, study selection and data abstraction process, analytical approach including planned sensitivity and subgroup analyses. Authors should also rate the quality of evidence looking beyond study limitation alone by using an approach such as the Grading of Recommendations Assessment, Development, and Evaluation (GRADE), which recognises such additional domains such as imprecision, inconsistency, indirectness and publication bias [6]. Critical steps of the systematic review process should be completed in duplicate to guard against random and systematic error and authors should provide readers with the information about who funded the studies included in the review, as well as their own potential conflicts of interests. To guard against publication bias, systematic review authors should also search for ongoing trials and unpublished studies through registries and abstract proceedings.

It is understood that the methodological handiwork that goes into the planning, execution and reporting of a systematic review do not assure clinical relevance or newsworthiness, nor does it address any issues surrounding the limited quality of studies that the review may be summarising. However, it is nevertheless a sine quae no to assure readers that they can be confident of the results. The new BJUI initiative will raise awareness for the issue of systematic review quality by providing a summary AMSTAR score to accompany each article. We hope that with this initiative we will provide a beacon for other specialty journals to follow, with the goal of raising the bar for all published systematic reviews and ultimately leading to improved patient care.

Philipp Dahm

 

Department of Urology, Minneapolis Veterans Administration Health Care System and University of Minnesota , MinneapolisMN, USA


References

 

1 Dahm P, Preminger GM. Introducing levels of evidence to publications in urology. BJU Int 2007; 100: 2467

 

 

 

4 HanJL, Gandhi S, Bockoven CG, Narayan VM, Dahm PThe landscape osystematic reviews in urology (1998 to 2015): an assessment of methodological quality. BJU Int 2016 [Epub ahead of print]. doi: 10.1111/bju.13653.

 

5 Narayan VM, Cone EB, Smith D, Scales CD Jr, Dahm P. Improved reporting of randomized controlled trials in the urologic literature. Eur Urol 2016; 70: 10449

 

6 Guyatt GH, Oxman AD, Vist GE et al. What is quality of evidence and why is it important to clinicians? BMJ 2008; 336: 9958

 

Editorial: Bringing clarity or confusion? The role of prostate-specific membrane antigen positron-emission/computed tomography for primary staging in prostate cancer

The use of 68Ga-labelled prostate-specific membrane antigen (PSMA) positron-emission tomography (PET)/CT for staging prostate cancer in Australia has reached almost plague-like proportions. Despite what must be admitted is little high-level evidence to guide us in the accuracy or appropriateness of this imaging technique for either primary staging or prostate cancer recurrence, hundreds of these scans are being performed every week around Australia, and in many cases we simply do not know what to do with the results. We performed the first such scan at our centre in Melbourne in August 2014, and were soon receiving 10 requests per day, with patients waiting up to 3 months to be scanned. Fast-forward 2 years, and there are now eight centres offering PSMA PET/CT in Melbourne, a city of 4.5 million people. Scans can be obtained within 24 h of referral and costs have dropped to €500. A similar situation exists in Germany where this imaging method was pioneered [1], and interest is also growing in Belgium, Italy, India and a number of other countries (the USA being a notable exception). But do we really understand the impact of the decision to perform PSMA/PET scanning, and do we have enough evidence to guide us on the most appropriate setting for its use?

The current interest in PSMA PET/CT has been triggered by the development of small molecule ligands which bind to the extracellular domain of the PSMA molecule, leading to increased sensitivity and specificity when compared with conventional imaging [2]. Previously, the use of PET imaging for prostate cancer detection was greatly limited by the relatively poor performance characteristics of choline-based PET/CT, and limited availability and high costs associated with this type of imaging. The introduction of 68Ga-labelled PSMA PET/CT has addressed many of these concerns, although high-quality evidence is still lacking to help guide its most appropriate utility. The best data exist for identification of prostate recurrence in patients with biochemical recurrence (BCR) after previous definitive therapy. In our recent systematic review and meta-analysis of this topic, we reported pooled data on 1309 men with BCR undergoing PSMA PET/CT [3]. When stratified by PSA level post-radical prostatectomy, positive scans are reported in 42, 58, 76 and 95% of patients with PSA levels of 0–0.2, 0.2–1, 1–2, and >2 ng/mL, respectively. Fewer data exist for the role of PSMA PET/CT in the primary staging setting.

In this interesting paper from some of our Australian colleagues, van Leeuwen et al. [4] report their experience of PSMA PET/CT in the primary staging setting, in particular to evaluate the performance of PSMA PET/CT to evaluate lymph node positivity in patients with intermediate- and high-risk disease, scheduled for radical prostatectomy. A total of 30 patients underwent preoperative PSMA PET/CT, of which 27 were stratified as high risk, and all subsequently underwent radical prostatectomy and pelvic lymph node dissection. In total, 11 patients (37%) had histologically proven lymph node metastases. On a per-patient basis, PSMA PET had a sensitivity of 64%, specificity of 95%, positive predictive value of 88%, and negative predictive value of 82%. The average size of positive lymph nodes not detected by PSMA PET/CT was 2.7 mm; therefore, in this population of patients with predominately high-risk prostate cancer, PSMA PET/CT had very high specificity and moderate sensitivity for lymph node metastasis detection.

In a larger experience from Munich, Maurer et al. [5] compared pathology findings of 130 patients with intermediate- and high-risk disease who underwent radical prostatectomy and pelvic lymph node dissection, with preoperative PSMA PET/CT or PET/MRI findings. They reported similar sensitivity, specificity and accuracy of 65.9, 98.9 and 88.5%, respectively. On receiver-operating characteristic analysis, PSMA-PET performed significantly better than conventional imaging alone on patient and template-based analyses (P = 0.002 and <0.001, respectively).

Just as there appears to be some clarity, however, in the role of PSMA PET/CT in patients with BCR, and in improving the detection of lymph node metastases preoperatively, there are many instances in which the high specificity of this scanning method leaves us in a decision-making quandary. As van Leeuwen et al. identified in their paper, and as we have frequently observed ourselves, PSMA PET/CT may identify prostate cancer in hitherto unidentified and unusual locations such as the mesorectum (Fig. 1). Disease may also be identified in quite distant locations despite relatively low PSA levels, thereby disrupting traditional management algorithms including the use of postoperative radiotherapy [6]. Should we alter patients’ management based on novel imaging, or should we assess the decision impact more formally in prospective studies? The answer should obviously be the latter, but the current plague of PSMA PET imaging means such decisions are already being taken in the absence of high-quality evidence.

image

Figure 1. 68Ga-labelled prostate-specific membrane antigen (PSMA) positron-emission tomography (PET)/CT in a 72-year-old man with biochemical recurrence after previous radical prostatectomy. His PSA level was 0.21 ng/mL and conventional staging including CT and bone scan showed no evidence of disease. PSMA PET/CT demonstrates intense avidity in an 11-mm mesorectal node near the recto-sigmoid junction on the left side. (a) CT demonstrates non-specific findings in area of subsequent avidity; (b) PSMA PET raw data demonstrating avidity in mesorectal node; (c) fused PSMA PET/CT image provides anatomical correlation; (d) coronal fused PET/CT image.

Nonetheless, PSMA PET imaging is here to stay, and will doubtless have a positive impact in improving decision-making in prostate cancer management as a result of the more accurate staging which it heralds. We must await more formal evaluation of the decision impact before defining the patient population who will benefit the most from this exciting imaging method.

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Declan G. Murphy, Urologist*,, Michael Hofman, Nuclear Medicine Physician, Nathan Lawrentschuk, Urologist*,§ and Tobias Maurer, Urologist

 

*Division of Cance r Surgery, Peter MacCallum Cancer Centre, University of Melbourne, Epworth Prostate Centre, Epworth Hospital, Department of Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, §Department of Surgery, The Austin Hospital, University of Melbourne, Heidelberg, Vic.Australia and Department of Urology, Technische Universitat Munchen, Klinikum rechts der Isar, Munich, Germany

 

References

 

 

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