urological oncology

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April Editorial: The BJUI’s clinical trials initiative

April 3, 2017/by John Davis

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.

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

1 Thompson IM, Goodman PJ, Tangen CM et al. The inﬂuence of ﬁnasteride on the development of prostate cancer. N Engl J Med 2003; 349: 215–24

2 Donovan JL, Hamdy FC, Lane A et al. Patient-reported outcomes after monitoring, surgery, or radiotherapy for prostate cancer. N Engl J Med 2016; 375: 1425–37

3 Lane A, Metcalfe C, Young GJ et al. Patient-reported outcomes in the ProtecT randomized trial of clinically localized prostate cancer treatments: study design, and baseline urinary, bowel and sexual function and quality of life. BJU Int 2016; 118: 869–79

4 Johnston TJ, Shaw GL, Lamb AD et al. Mortality among men with advanced prostate cancer excluded from the ProtecT trial. Eur Urol 2017; 71: 381–8

5 Yaxley JW, Coughlin GD, Chambers SK et al. Robot-assisted laparoscopic prostatectomy versus open radical retropubic prostatectomy: early outcomes from a randomised controlled phase 3 study. Lancet 2016; 388: 1057–66

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

Controversies in management of high-risk prostate and bladder cancer

October 12, 2015/by Stacy Loeb

Recently, there has been substantial progress in our understanding of many key issues in urological oncology, which is the focus of this month’s BJUI. One of the most substantial paradigm shifts over the past few years has been the increasing use of radical prostatectomy (RP) for high-risk prostate cancer and increasing use of active surveillance for low-risk disease [1,2].

Consistent with these trends, this month’s BJUI features several useful articles on the management of high-risk prostate cancer. The ﬁrst article by Abdollah et al. [3] reports on a large series of 810 men with D’Amico high-risk prostate cancer (PSA level >20 ng/mL, Gleason score 8–10, and/or clinical stage ≥T2c) undergoing robot-assisted RP (RARP). Despite high-risk characteristics preoperatively, 55% had specimen-conﬁned disease at RARP, which was associated with higher 8-year biochemical recurrence-free (72.7% vs 31.7%, P < 0.001) and prostate cancer-speciﬁc survival rates (100% vs 86.9%, P < 0.001). The authors therefore designed a nomogram to predict specimen-conﬁned disease at RARP for D’Amico high-risk prostate cancer. Using PSA level, clinical stage, maximum tumour percentage quartile, primary and secondary biopsy Gleason score, the nomogram had 76% predictive accuracy. Once externally validated, this could provide a useful tool for pre-treatment assessment of men with high-risk prostate cancer.

Another major controversy in prostate cancer management is the optimal timing of postoperative radiation therapy (RT) for patients with high-risk features at RP. In this month’s BJUI, Hsu et al. [4] compare the results of adjuvant (≤6 months after RP with an undetectable PSA level), early salvage (administered while PSA levels at ≤1 ng/mL) and late salvage RT (administered at PSA levels of >1 ng/mL) in 305 men with adverse RP pathology from the USA Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry. At 6.2 years median follow-up, late salvage RT was associated with signiﬁcantly higher rates of metastasis and/or prostate cancer-death. By contrast, there was no difference in prostate cancer mortality and/or metastasis between early salvage vs adjuvant RT. A recent study from the USA National Cancer Data Base reported infrequent and declining use of postoperative RT within 6 months for men with adverse RP pathology, from 9.1% in 2005 to 7.3% in 2011 [5]. As we await data from prospective studies comparing adjuvant vs early salvage RT, the results of Hsu et al. [4] are encouraging, suggesting similar disease-speciﬁc outcomes if salvage therapy is administered at PSA levels of <1 ng/mL.

Finally, this issue’s ‘Article of the Month’ by Baltaci et al. [6] examines the timing of second transurethral resection of the bladder (re-TURB) for high-risk non-muscle-invasive bladder cancer (NMIBC). The management ofbladder cancer at this stage is a key point to improve the overall survival of bladder cancer. Re-TURB is already recommended in the European Association of Urology guidelines [7], but it remains controversial as to whether all patients require re-TURB and what timing is optimal. The range of 2–6 weeks after primary TURB was established based on a randomised trial assessing the effect of re-TURB on recurrence in patients treated with intravesical chemotherapy [8], but it has not been subsequently tested in a randomised trial. Baltaci et al. [6], in a multi-institutional retrospective review of 242 patients, report that patients with high-risk NMIBC undergoing early re-TURB (14–42 days) have better recurrence-free survival vs later re-TURB (73.6% vs 46.2%, P < 0.01). Although prospective studies are warranted to conﬁrm their results, these novel data suggest that early re-TURB is signiﬁcantly associated with lower rates of recurrence and progression.

References

1 Cooperberg MR, Carroll PR. Trends in management for patients with localized prostate cancer, 1990–2013. JAMA 2015; 314: 80–2

2 Loeb S, Berglund A, Stattin P. Population based study of use and determinants of active surveillance and watchful waiting for low and intermediate risk prostate cancer. J Urol 2013; 190: 1742–9

3 Abdollah F, Klett DE, Sood A et al. Predicting pathological outcomes in patients undergoing robot-assisted radical prostatectomy for high- risk prostate cancer: a preoperative nomogram. BJU Int 2015; 116: 703–12

4 Hsu CC , Paciorek AT, Cooperberg MR, Roach M 3rd, Hsu IC, Carroll PR. Postoperative radiation therapy for patients at high-risk of recurrence after radical prostat ectomy: does timing matter? BJU Int 2015; 116: 713–20

5 Sineshaw HM, Gray PJ, Efstathiou JA, Jemal A. Declining use of radiotherapy for adverse features after radical prostatectomy: results from the National Cancer Data Base. Eur Urol 2015; [Epub ahead of print]. DOI: 10.1016/ j.eururo.2015.04.003

6 Baltacı S, Bozlu M, Yıldırım A et al. Signiﬁcance of the interval between ﬁrst and second transurethral resection on recurrence and progression rates in patients with high-ris k non-muscle-invasive bladder cancer treated with maintenance intravesical Bacillus Calmette-Guerin. BJU Int 2015; 116: 721–6

7 Babjuk M, Bohle A, Burger M et al. European Association of Urology Guidelines on Non-Muscle-Invasive Bladder Cancer (Ta, T1, and CIS). Available at: https://uroweb.org/wp-content/uploads/EAU-Guidelines- Non-muscle-invasive-Bladder-Cancer-2015-v1.pdf. Accessed September 2015

8 Divrik RT, Yildirim U, Zorlu F, Ozen H. The effect of repeat transurethral resection on recurrence and progression rates in patients with T1 tumors of the bladder who received intravesical mitomycin: a prospective, randomized clinical trial. J Urol 2006; 175: 1641–4

Stacy Loeb – Department of Urology, Population Health, and the Laura and Isaac Perlmutter Cancer Center, New York University, New York City, NY, USA

Maria J. Ribal – Department of Urology, Hospital Clinic, University of Barcelona, Barcelona, Spain

Clever surgeons and challenging study endpoints

August 18, 2015/by John Davis

Intraoperative in vivo tracking of a periprostatic nerve with multiphoton microscopy in rat model.

In the last 6 months, the BJUI editorial team has evaluated an average of 59 urological oncology papers per month with an average acceptance rate of 16%. We receive additional papers for our ‘Translational Science’ section. Studies with high-quality methods are given the highest priority. Other papers compete well if they are highly applicable to clinical practice (i.e. comparative, multicentre, multi-surgeon design) and/or show us new ideas in surgical technique, re-designed study endpoints, or explore new sources of data. For translational science, the best candidates are studies that look at new diagnostic tests in humans and beyond simple immunostaining techniques. We want to evaluate biomarkers likely to be validated and translated into a clinical test. Clinical impact will be even higher if a biomarker is linked to a therapy outcome rather than just a risk estimate. We want our papers to guide us to better outcomes for our patients, hopefully control healthcare costs, and, yes, be well-cited in the literature.

Our review process is tough but fair, and we congratulate and highlight three authorship groups for acceptance into this month’s issue of BJUI. The theme of ‘clever surgeons and challenging study endpoints’ is well illustrated by all three groups. Zargar et al. [1] report on an exclusive database of high-volume minimally invasive surgeons who have tackled the partial nephrectomy option for small renal masses. The comparison is simple in concept and retrospective in design, but what they have done is to significantly increase the outcome measures into a ‘trifecta’ concept in perioperative outcomes (previously reported) with an even more stringent ‘optimal outcome’ endpoint that includes renal function preservation. With a database of 1185 robotic and 646 laparoscopic cases, the robotic procedures showed superior trifecta results (70% vs 33%), complication rates (14.8% vs 20.9%), positive surgical margin rates (3.2% vs 9.7%), and warm ischaemia time (18 vs 26 min). The optimal outcome endpoint included a minimum 90% estimated GFR (eGFR) preservation and no chronic kidney disease upstaging. Only the robotic cohort had sufficient data available and the rate was 38.5%. The latter figure is an interesting challenge, as defining such a high threshold for success challenges surgical technique and allows more room to identify incremental advancement. This may be the largest study of its kind, but non-randomised and with limitations discussed in peer review such as the learning curve influence, use of eGFR as an endpoint with two kidneys, and incomplete data. The definitions used are of interest and the field could use some uniformity moving forward in measuring perioperative and long-term benchmarks of quality.

Durand et al. [2] give us a glimpse into the future of surgery, a science fiction world of prostate surgery where nerves and prostatic glands can be colour coded and seen at a microscopic level in real time. The pictures stand for themselves, especially Fig. 1. If such imaging can be integrated into technique decisions, and perhaps future instrument designs, then perhaps we will have a whole new wave of studies possible on linking surgical technique to improved functional and oncological outcomes after radical prostatectomy. The paper has a nice depth in detail, methods, results, as well as narratives in solving technical problems with novel technology.

This issue’s ‘Article of the Month’ by Gavin et al. [3] is a different look at the question of morbidity after localised prostate cancer treatments, specific to long-term care at >2 years from treatment. The database is from a cancer registry and they have an impressive 54% response rate from a population that is 2–18 years from diagnosis. Rather than Likert-like scales of symptom severity, they simply look at ‘current’ vs ‘ever had’ symptoms and look at the total burden including multiple/overlapping symptoms. Although this may not be as robust and validated as the Expanded Prostate Cancer Index Composite (EPIC) instrument, the simple phrasing of ‘current’ vs ‘ever had’ is probably capturing a very high proportion of symptoms rather than dismissing them if minor or in the past. Again, we see more erectile dysfunction after radical prostatectomy and radiation with hormonal therapy, and more bowel symptoms after radiation therapy. Hormone therapy patients have hot flashes and fatigue, and watchful-waiting patients have some advantages but are certainly not free of symptoms. The burden of symptoms is interesting, nine of 10 reported at least one of seven key symptoms at some point and three of four are current. Therefore, as the authors indicate, ≈75% of prostate cancer survivors will have ongoing symptoms needing follow-up care. This is a significant database resource adding to our understanding of long-term outcomes of patients with prostate cancer and supporting the significance of the Durand et al. [2] study that may show the way forward towards reducing such burdens of disease treatment.

References

1 Zargar H, Al laf ME, Bhayani S et al. Trifecta and optimal perioperative outcomes of robotic and laparoscopic partial nephrectomy in surgical treatment of small renal masses: a multi-institutional study. BJU Int 2015; 407–14

2 Durand M, Jain M, Aggarwal A et al. Real-time in vivo periprostatic nerve tracking using multiphoton microscopy in a rat survival surgery model: a promising pre-clinical study for enhanced nerve-sparing surgery. BJU Int 2015; 478–86

3 Gavin AT, Drummond FJ, Donnelly C, O’Leary E, Sharp L, Kinnear HR. Patient-reported ‘ever had’ and ‘current’ long-term physical symptoms after prostate cancer treatments. BJU Int 2015; 397–406

John W. Davis, MD
Associate Editor, BJUI

Highlights from #BAUS15

June 24, 2015/by Rebecca Tregunna

#BAUS15 started to gain momentum from as early as the 26^th June 2014 and by the time we entered the Manchester Central Convention Complex well over 100 tweets had been made. Of course it wasn’t just Twitter that started early with a group of keen urologists cycling 210 miles to conference in order to raise money for The Urology Foundation.

Monday 15^th June 2015

By the time the cyclists arrived conference was well under way with the andrology, FNUU and academic section meetings taking place on Monday morning:

The BJU International Prize for the Best Academic Paper was awarded to Richard Bryant from the University of Oxford for his work on epithelial-to-mesenchymal transition changes found within the extraprostatic extension component of locally invasive prostate cancers.
Donna Daly from the University of Sheffield received the BJUI John Blandy prize for her work on Botox, demonstrating reductions in afferent bladder signaling and urothelial ATP release.

Professor Reisman’s talk on ‘Porn, Paint and Piercing’ as expected drew in the crowds and due to a staggering 44% complication rate with genital piercings it is important for us to try to manage these without necessarily removing the offending article as this will only serve to prevent those in need from seeking medical attention.
With the worsening worldwide catastrophe of antibiotic resistance, the cycling of antibiotics for prevention of recurrent UTIs is no longer recommended. Instead, Tharani Nitkunan provided convincing evidence for the use of probiotics and D-Mannose.

The afternoon was dominated by the joint oncology and academic session with Professor Noel Clarke presenting the current data from the STAMPEDE trial. Zolendronic acid conferred no survival benefit over hormones alone and consequently has been removed from the trial (stampede 1). However, Docetaxal plus hormones has shown benefit, demonstrated significantly in M1 patients with disease-free survival of 65 months vs. 43 months on hormones alone (Hazard ratio 0.73) (stampede 2). This means that the control arm of M1 patients who are fit for chemotherapy will now need to be started on this treatment as the trial continues to recruit in enzalutamide, abiraterone and metformin arms.

The evening was rounded off with the annual BAUS football tournament won this year by team Manchester (obviously a rigged competition!), whilst some donned the

lycra and set out for a competition at the National Cycle Centre. For those of us not quite so energetic, it was fantastic to catch up with old friends at the welcome drinks reception.

Tuesday 16^th June 2015

Tuesday kicked off bright and early with Professor John Kelly presenting results from the BOXIT clinical trial, which has shown some benefit over standard treatment of non-muscle invasive bladder cancer, but with significant cardiovascular toxicity.

The new NICE bladder cancer guidelines were presented with concerns voiced by Professor Marek Babjuk over discharging low-risk bladder cancer at 12 months given a quoted 30-50% five-year recurrence risk. Accurate risk stratification, it would seem, is going to be key.

The President’s address followed along with the presentation of the St. Peter’s medal for notable contribution to the advancement of urology, which was presented to Pat Malone from Southampton General Hospital. Other medal winners included Adrian Joyce who received the BAUS Gold Medal, and the St. Paul’s medal went to Mark Soloway.

A plethora of other sessions ensued but with the help of the new ‘native’ BAUS app my programme was already conveniently arranged in advance:

‘Heartsink Conditions’ included pelvic and testicular pain and a fascinating talk by Dr Gareth Greenslade highlighted the importance of early and motivational referral to pain management services once no cause has been established and our treatments have been exhausted. The patient’s recovery will only start once we have said no to further tests: ‘Fix the thinking’

Poster sessions are now presented as ‘e-posters’, abolishing the need to fiddle with those little pieces of Velcro and allowing for an interactive review of the posters.

Pravisha Ravindra from Nottingham demonstrated that compliance with periodic imaging of patients with asymptomatic small renal calculi (n=147) in primary care is poor, and indeed, these patients may be better managed with symptomatic imaging and re-referral as no patients required intervention based on radiograph changes alone.

Archana Fernando from Guy’s presented a prospective study demonstrating the value of CTPET in the diagnosis of malignancy in patients with retroperitoneal fibrosis (n=35), as well as demonstrating that those with positive PET are twice as likely to respond to steroids.

Wednesday 17^th June 2015

Another new addition to the programme this year was the Section of Endourology ‘as live surgery’ sessions. This was extremely well received and allowed delegates to benefit from observing operating sessions from experts in the field whilst removing the stressful environment and potential for risk to patient associated with live surgery. This also meant that the surgeon was present in the room to answer questions and talk through various steps of the operation allowing for a truly interactive session.
Wednesday saw multiple international speakers dominating the Exchange Auditorium:

The BJU International guest lecture was given by Professor Hendrik Van Poppel: a heartfelt presentation describing what he believes to be the superiority of surgery over radiotherapy for high-risk localised prostate cancer.
The Urology Foundation presented the Research Scholar Medal to Ashwin Sachdeva from Freeman Hospital, Newcastle for his work on the ‘Role of mitochondrial DNA mutations in prostate carcinogenesis’. This was followed by an inspiring guest lecture by Inderbir Gill on ‘Robotic Urologic Oncology: the best is yet to come’ with the tag line ‘the only thing that should be open in 2015 is our minds’
Robotic Surgery in UK Urology: Clinical & Commissioning Priorities was a real highlight in the programme with talks from Jim Adshead and Professor Jens-Uwe Stolzenburg focussing on the fact that only 40% of T1a tumours in the UK were treated with partial (as opposed to radical) nephrectomy, and that the robot really is the ‘game-changer’ for this procedure. Inderbir Gill again took to the stage to stress that all current randomised trials into open vs. robotic cystectomy have used extracorporeal reconstruction and so do not reflect the true benefits of the robotic procedure as the dominant driver of complications is in the open reconstruction.

These lectures were heard by James Palmer, Clinical Director of Specialised Commissioning for NHS England who then discussed difficulties in making decisions to provide new technologies, controlling roll out and removing them if they show no benefit. Clinical commissioning policies are currently being drafted for robotic surgery in kidney and bladder cancer. This led to a lively debate with Professor Alan McNeill having the last word as he pointed out that what urologists spend on the robot to potentially cure cancer is a drop in the ocean compared with what the oncologists spend to palliate!

Thursday 18^th June 2015

The BJU International session on evidence-based urology highlighted the need for high-quality evidence, especially in convincing commissioners to spend in a cash-strapped NHS. Professor Philipp Dahm presented a recent review in the Journal of Urology indicated that the quality of systematic reviews in four major urological journals was sub-standard. Assistant Professor Alessandro Volpe then reviewed the current evidence behind partial nephrectomy and different approaches to this procedure.

Another fantastic technology, which BAUS adopted this year, was the BOD-POD which allowed delegates to catch-up on sessions in the two main auditoria that they may have missed due to perhaps being in one of the 21 well designed teaching courses that were available this year. Many of these will soon be live on the BAUS website for members to view.

The IBUS and BAUS joint session included a lecture from Manoj Monga from The Cleveland Clinic, which led to the question being posed on Twitter: ‘Are you a duster or a basketer?’The audience was also advised to always stent a patient after using an access sheath unless the patient was pre-stented.

The updates session is always valuable especially for those studying for the FRCS (Urol) exam with far too many headlines to completely cover:

Endourology: The SUSPEND trial published earlier this year was a large multi-centre RCT that showed no difference in terms of rates of spontaneous passage of ureteric stone, time to stone passage or analgesic use between placebo, tamsulosin and nifedipine. There was a hot debate on this: should we be waiting for the meta-analysis or should a trial of this size and design be enough to change practice?
Oncology-Prostate: The Klotz et al., paper showed active surveillance can avoid over treatment, with 98% prostate cancer survival at 10 years.
Oncology-Kidney: Ellimah Mensah’s team from Imperial College London (presented at BAUS earlier in the week) demonstrated that over a 14-year period there were a higher number of cardiovascular-related admissions to hospital in patients who have had T1 renal tumours resected than the general population, but no difference between those who have had partial or radical nephrectomy.
Oncology-Bladder: Arends’s team presented at EAU in March on the favourable results of hyperthermic mitomycin C vs. BCG in the treatment of intermediate- and high-risk bladder cancer.
Female and BPH: The BESIDE study has demonstrated increased efficacy with combination solifenacin and mirabegron.
Andrology: Currently recruiting in the UK is the MASTER RCT to evaluate synthetic sling vs. artificial sphincter in men with post-prostatectomy urinary incontinence.

Overall BAUS yet again put on a varied and enjoyable meeting. The atmosphere was fantastic and the organisers should be proud of the new additions in terms of allowing delegates to engage with new technologies, making for a memorable week. See you all in Liverpool!

Rebecca Tregunna, Urological Trainee, West Midlands Deanery @rebeccatregunna

Dominic Hodgson, Consultant Urologist, Portsmouth @hodgson_dominic

Future Directions in Urological Oncology

March 31, 2015/by R. Houston Thompson

The field of urological oncology is rapidly changing. For example, robotic surgery, targeted therapy, and ablation techniques are oncological options that were in their infancy 10 years ago and are now mainstream in many areas of the world. Additionally, immunotherapy has recently become a promising avenue in multiple urological cancers. As we move forward, expect to see a larger presence of urological oncology literature obtained via social media, which BJUI has initiated and subsequently set the standard for the field. Related to this, this month’s edition of BJUI includes four online ‘Articles of the Week’, with each focusing on urological oncology.

Using data from the pro-PSA Multicentric European Study (PROMEtheuS) project, Abrate et al. [1] evaluated the utility of the Prostate Health Index (PHI) in 142 obese (body mass index BMI >30 kg/m²) men who underwent a prostate biopsy for an abnormal DRE or elevated PSA level. Among the 142 patients, 65 (45.8%) were found to harbour prostate cancer. Using the PHI threshold of 35.7, the authors determined that 46 (32.4%) negative biopsies could have been avoided while six (9.2%) cancers would have been missed. Related to this, Salami et al. [2] compared the cancer detection rates of MRI fusion biopsy vs standard 12-core TRUS-guided biopsy in 140 men with a previous negative prostate biopsy and a lesion appreciated on a multiparametric MRI. While the cancer detection rates were similar overall, the MRI fusion biopsy was more likely to detect clinically significant prostate cancer (48% vs 31%), defined as Gleason ≥7 or Gleason 6 with a lesion volume of >0.2 mL on MRI. In an era where over-diagnosis of prostate cancer is commonplace, data to better stratify patients who need (or do not need) a prostate biopsy and enhanced ways to identify clinically significant prostate cancers are of paramount importance.

Soares et al. [3] report their results among 1 138 contemporary laparoscopic radical prostatectomy patients who had at least 5 years of follow-up. Only one case required an open conversion and the transfusion rate was merely 0.5%. At last follow-up, 85% of patients had an undetectable PSA level, 94% of patients were continent, and 77% of non-diabetic men aged <70 years retained potency. These impressive single-surgeon results further suggest that the morbidity of prostate cancer surgery has diminished with increasing time and experience.

Additionally, Tolchard et al. [4] prospectively evaluated 105 patients with bladder cancer with preoperative cardiopulmonary exercise testing prior to radical cystectomy. Patients who received neoadjuvant chemotherapy were excluded and there was a 6% perioperative death rate with 90 days of follow-up. The results suggest that patients with poor cardiopulmonary reserve along with hypertension are at higher risk of perioperative complications and prolonged hospital stay; median length of stay was 22 and 9 days for patients with and without a complication. Furthermore, while only 2% of patients had a preoperative diagnosis of heart failure, there were a significant proportion of patients (50% in this study) found to have moderate-to-severe heart failure based on preoperative cardiopulmonary exercise testing. These provocative results suggest that the urological community should further investigate the utility of routine cardiopulmonary exercise testing in patients undergoing radical cystectomy along with the optimal incorporation of such testing in patients receiving neoadjuvant chemotherapy.

References

1 Abrate A, Lazzeri M, Lughezzani Gi et al. Clinical performance of the Prostate Health Index (PHI) for the prediction of prostate cancer in obese men: data from the PROMEtheuS project, a multicentre European prospective study. BJU Int 2015;115:537–45.

2 Salami SS, Ben-Levi E, Yaskiv O et al. In patients with a previous negative prostate biopsy and a suspicious lesion on magnetic resonance imaging, is a 12-core biopsy still necessary in addition to a targeted biopsy? BJU Int 2015;115:562–70.

3 Soares R, Di BenedettoA, Dovey Z, Bott S, McGregor RG, Eden CG. Minimum 5-year follow-up of 1138 consecutive laparoscopic radical prostatectomies. BJU Int 2015;115:546–53.

4 Tolchard S, Angell J, Pyke M et al. Cardiopulmonary reserve as determined by cardiopulmonary exercise testing correlates with length of stay and predicts complications after radical cystectomy. BJU Int2015;115:554–61.

R. Houston Thompson – BJUI Consulting Editor (Oncology)

Mayo Clinic, Rochester, MN, USA

Urological oncology in the BJUI

September 4, 2013/by John Davis

Urological oncology is increasingly multi-disciplinary, and hence competitive for high impact thought leadership. Innovation leading to paradigm changes may come from a number of different ideas and sources. Effective leadership in our specialty certainly requires technical innovations in surgical treatments, but also pivotal roles in improving the process of diagnosis, staging, patient counselling, multi-modal therapy, and ultimately evidence-based clinical guidelines. The ultimate end-result of innovation is a peer reviewed publication, and at the BJUI we wish to bring you nothing but the highest quality.

Our daily lives are increasingly busy with our varying mixtures of clinical work, teaching, administration, and research. How much time do we have to read a surgical journal? It is an important part of our learning, but we must be efficient to squeeze it into a busy day. Keeping this in mind, the Editorial Board is more selective than ever in the papers that make it into the BJUI. Each paper we accept needs to represent something valuable to the reader and to our science, such as a technical innovation, large study of a new method to fix an unmet need, multi-institutional validation trial, or updated guideline. For this to work, we need fair and efficient peer reviewers, and high quality submissions.

In this month’s BJUI, we see encouraging work from multiple talented authorship groups who address a plethora of unmet needs. These papers show the diversity of impact the Editorial team is looking for in BJUI urological oncology submissions.

Prostate cancer, of course, is a common topic for new submissions and subsequent citations. In the field of localised prostate cancer and PSA screening, the recent U.S. Preventive Services Task Force (USPSTF) report was critical of our diagnostic practice results in terms of biopsy related complications and, of course, negative (a.k.a. unnecessary, a term we should drop) biopsies. I must confess that I am still stuck in the tradition of the PSA/DRE as the key driver of my recommendation for a biopsy, and several informal ‘raise your hand’ polls at meetings have produced little movement when asked if anyone has adopted newer calculators that incorporate TRUS volume. Why not change? The numbers certainly seem reasonable: an area under the curve (AUC) of 0.71 for DRE/PSA and 0.77 for the risk calculator. You can even make a crude DRE-volume estimate and improve your odds – AUC of 0.73 without and 0.77 with DRE-volume. If that sounds of interest, then perhaps the study by Carlsson et al. in this issue may interest you with their biomarker panel of kallikreins that can do the same work as the combined clinical efforts and reach AUCs of 0.76 alone, or 0.792 if you still want to add the DRE and TRUS volume. I agree with the authors, that this is perhaps a simpler model, which may allow the physician and patient some time to have a look at their risk of a positive biopsy and make a decision, rather than the idea of the last minute TRUS volume that is supposed to put the brakes on a biopsy at a certain size. With further refinement, we can all learn new thresholds for biopsy that are better selected, and in the future should always be calculated as overall cancers detected/missed and high-grade cancers detected/missed.

In addition, the USPSTF criticised the toxicity of a biopsy, and drug-resistant sepsis is an increasing problem. Symons et al. present an instructive series of transperineal biopsies and results, and they seem to have solved the sepsis problem (0.2%), but must weigh the added cost of anaesthesia, physician time, and no obvious difference in bleeding/other minor complications. I am increasingly interested in re-utilising this technique, which previously was only for third-line saturation biopsies. If you are also convinced, Kuru et al. present a tour-de-force presentation of transperineal technique, terminology, and data collection for a multi-centre collaboration.

Finally, in a must-read special article, Carter expands upon the recent AUA guidelines on PSA screening that were intensely debated, especially the recommendations against routine screening in men aged <55 years. Guidelines are an interesting area of study, and can vary in outcome based upon who is on them and what methodology/objectives are selected. If the guideline is meant to be best clinical practice, than the personnel can certainly be influential. However, if the guideline is meant to emphasise evidence-based recommendations, then in theory, any panel of experts will arrive at a similar place. This is the essential message from Carter, that the revised guidelines are meant to reflect the evidence, and currently we do not have level 1 evidence that involved screening men aged <55 years.

Closing this month in ‘Urological Oncology’, Cindolo et al. report an accuracy/generalizability study of the Karakiewicz nomograms for cancer-specific survival with RCC. These articles are, of course, largely statistical exercises, but very necessary, as we define populations suitable for surgery only vs those in need of neoadjuvant/adjuvant inclusion. Wong et al. conclude the month with an innovative report on office-based laser ablation of non-muscle-invasive bladder cancer using local anaesthesia, mostly in an elderly population. The study protocol allowed photodynamic diagnosis, and includes a cost analysis. The results certainly support continued use in this population where we commonly wish to avoid the morbidity of repeat general anaesthetics.

John W. Davis, MD, FACS
Associate Editor, BJUI

Original publication of this editorial can be found at: doi: 10.1111/bju.12380. BJUI 2013; 112: 531–532.

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