Anders Bjartell, John Yaxley & the BJUI team discuss surgeon heterogeneity in the Swedish LAPPRO study published in the BJUI March 2021.
Read the paper here: bjui.pub/BJUI-LAPPRO
Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.
In addition to this post, there is an editorial written by a prominent member of the urological community. Please use the comment buttons below to join the conversation.
If you only have time to read one article this week, we recommend this one.
Amandeep Dosanjh*†, Simon Baldwin*, Jemma Mytton*†, Dominic King†, Nigel Trudgill†, Mohammed Belal‡ and Prashant Patel†
*Department of Health Informatics, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK , †Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK and ‡Department of Urology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
To consider the provision of post‐radical prostatectomy (RP) continence surgery in England.
Patients with an Office of Population Census and Surveys Classification of Interventions and Procedures, version 4 code for an artificial urinary sphincter (AUS) or male sling between 1 January 2010 and 31 March 2018 were searched for within the Hospital Episode Statistics (HES) dataset. Those without previous RP were excluded. Multivariable logistic regressions for repeat AUS and sling procedures were built in stata. Further descriptive analysis of provision of procedures was performed.
A total of 1414 patients had received index AUS, 10.3% of whom had undergone prior radiotherapy; their median follow‐up was 3.55 years. The sling cohort contained 816 patients; 6.7% of these had received prior radiotherapy and the median follow‐up was 3.23 years. Whilst the number of AUS devices implanted had increased each year, male slings peaked in 2014/2015. AUS redo/removal was performed in 11.2% of patients. Patients in low‐volume centres were more likely to require redo/removal (odds ratio [OR] 2.23 95% confidence interval [CI] 1.02–4.86; P = 0.045). A total of 12.0% patients with a sling progressed to AUS implantation and 1.3% had a second sling. Patients with previous radiotherapy were more likely to require a second operation (OR 2.03 95% CI 1.01–4.06; P = 0.046). Emergency re‐admissions within 30 days of index operation were 3.9% and 3.6% fewer in high‐volume centres, for AUS and slings respectively. The median time to initial continence surgery from RP was 2.8 years. Increased time from RP conferred no reduced risk of redo surgery for either procedure.
There is a volume effect for outcomes of AUS procedures, suggesting that they should only be performed in high‐volume centres. Given the known impact of incontinence on quality of life, patients should be referred sooner for post‐prostatectomy continence surgery.
Post‐prostatectomy urinary incontinence (UI) is a well‐recognised consequence of radical prostatectomy carried out as treatment for organ‐confined prostate cancer. This interesting article [1] reviews the in-practice surgical management of post‐prostatectomy UI in England over an 8‐year period, using the Hospital Episodes Statistics (HES) database.
In total, 1414 patients had an artificial urinary sphincter (AUS) implanted, with a median follow‐up of 3.55 years. In contrast, 816 patients were treated with a male sling, with a median follow‐up of 3.23 years. Post‐prostatectomy AUS implantation was performed in 49 centres and male sling surgery in 48 centres. It is not clear whether the same centres were involved in implanting both devices; it is however of note that for AUS implantation, 34.7% of the centres performed fewer than six post‐prostatectomy AUS implantations over the 8‐year period and 18.4% performed >50 in the same period. Both re‐do and removal surgery of AUS had some association with low‐volume providers; 7.7% of patients received a second AUS and 0.8% had undergone the procedures three or more times. A total of 12.5% of patients had an AUS re‐do or removal; 0.6% of these were within 6 weeks of the index procedure. Prior sling surgery did not predict an increased likelihood of re‐do or removal. Similarly, 33.3% of centres performed less than six post‐prostatectomy sling surgeries over the 8‐year period and only 4.3% performed >50 procedures. There was no association of centre volume with the likelihood of sling revision.
With reference to the potential impact of radiotherapy (RT), in two centres there was a 19.3% incidence of patients with prior RT compared to 9.4% for the other provider groups. Prior RT was associated with a two‐fold increase risk of sling revision. The authors conclude that previous RT did not confer a higher risk of re‐do or removal of AUS.
As with any real‐life practice study, there are potential limitations to interpretation of the data.
The most important take home message from this article is the importance of undergoing post‐prostatectomy UI surgery in a high‐volume centre. A prospective database should be established to document the indications for, as well as outcomes, following both AUS and sling surgery in real‐life clinical practice. Certainly, this is likely to become mandatory under European Commission law and it would be of importance for this to be likewise implemented in the UK in the future.
by Christopher Chapple
Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.
In addition to the article itself, there is an editorial written by a prominent member of the urological community and a podcast prepared by one of our Resident podcasters; we invite you to use the comment tools at the bottom of each post to join the conversation.
If you only have time to read one article this week, we recommend this one.
Fady K. Ghobrial, Ahmed Shoma, Ahmed M. Elshal, Mahmoud Laymon, Nasr El-Tabey, Adel Nabeeh and Ahmed A. Shokeir
Urology Department, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt
To test the non‐inferiority of bipolar transurethral vaporization of the prostate (TUVP) compared to GreenLight laser (GL) photoselective vaporization of the prostate (PVP) for reduction of benign prostatic hyperplasia‐related lower urinary tract symptoms in a randomized trial.
Eligible patients with prostate volumes of 30–80 mL were randomly allocated to GL‐PVP (n = 58) or bipolar TUVP (n = 61). Non‐inferiority of symptom score (International Prostate Symptom Score [IPSS]) at 24 months was evaluated. All peri‐operative variables were recorded and compared. Urinary (IPSS, maximum urinary flow rate and post‐void residual urine volume) and sexual (International Index of Erectile Function‐15) outcome measures were evaluated at 1, 4, 12 and 24 months. Need for retreatment and complications, change in PSA level and health resources‐related costs of both procedures were recorded and compared.
Baseline and peri‐operative variables were similar in the two groups. At 1, 4, 12 and 24 months, 117, 116, 99 and 96 patients, respectively, were evaluable. Regarding urinary outcome measures, there was no significant difference between the groups. The mean ± sd IPSS at 1 and 2 years was 7.1 ± 3 and 7.9 ± 2.9 (P = 0.8), respectively, after GL‐PVP and 6.3 ± 3.1 and 7.2 ± 2.8, respectively, after bipolar TUVP (P = 0.31). At 24 months, the mean difference in IPSS was 0.7 (95% confidence interval −0.6 to 2.3; P = 0.6). The median (range) postoperative PSA reduction was 64.7 (25–99)% and 65.9 (50–99)% (P = 0.006) after GL‐PVP, and 32.1 (28.6–89.7)% and 39.3 (68.8–90.5)% (P = 0.005) after bipolar TUVP, at 1 and 2 years, respectively. After 2 years, retreatment for recurrent bladder outlet obstruction was reported in eight (13.8%) and 10 (16.4%) patients in the GL‐PVP and bipolar TUVP groups, respectively (P = 0.8). The mean estimated cost per bipolar TUVP procedure was significantly lower than per GL‐PVP procedure after 24 months (P = 0.01).
In terms of symptom control, bipolar TUVP was not inferior to GL‐PVP at 2 years. Durability of the outcome needs to be tracked. The greater cost of GL‐PVP compared with bipolar TUVP is an important concern.
The paper by Ghobrial et al. [1] confirms that bipolar electrocautery vaporization is more cost‐effective than GreenLight Laser vaporization, as the two techniques are equally effective but GreenLight vaporization is more costly in the smaller prostates being studied.
Underpinning the analysis was a well‐conducted randomized controlled trial, showing equivalent peri‐operative and postoperative measures with the two procedures and no difference in the primary endpoint of IPSS reduction at 2 years. The two techniques were performed in a similar manner and were equally efficient and safe as expected.
Philosophically, the clinical results are both unsurprising and expected, and confirm the long‐held belief that the energy source employed for vaporization and, for that matter, enucleation, is of secondary concern compared to the skill and dedication of the operator. The technique in either case should result in comparable efficacy, leaving cost‐effectiveness to be an important way to help both urologists and administrators discriminate between them.
Although the costs are not necessarily going to be comparable with those in other jurisdictions, this will apply equally to both treatments and this study therefore represents an excellent attempt to cost both procedures, removing equivalent costs. Importantly, this assessment included the costs of both readmissions and interventions over the full 24‐month period. This captures the bulk of the important complications after these types of procedures and adds to the validity of the findings.
The big difference between the costs of the two treatments being studied is, of course, ‘capital equipment including maintenance’. The single‐use fibre model rather than the cost of the machine has been the mainstay for the profitability of laser companies since the inception of laser prostatectomy. The maintenance contract has been a further cost, which is always underestimated. Reusability of the laser fibres is one way of diminishing per‐procedure costs, but is only consistently possible for Holmium end‐fire fibres [2]. The fact that the authors estimate of these costs was a ‘case share in 5‐year budget plan’ also suggests that the true cost of the use of the GreenLight laser is underestimated.
With the burgeoning number of new techniques and technologies for the treatment of BPH emerging, and new treatment paradigms being proposed, let alone the increasingly negative focus on medical waste [3] and the increasing use of single‐use disposable handpieces/tubing/drapes/fibres, articles such as this are timely. A standardized methodology for assessing the cost‐effectiveness of treatments for BPH is needed and should be an essential part of pivotal studies and therefore the regulatory approval processes.
by Peter Gilling
Maria Uloko is a Urology Resident at the University of Minnesota Hospital.
To test the non‐inferiority of bipolar transurethral vaporization of the prostate (TUVP) compared to GreenLight laser (GL) photoselective vaporization of the prostate (PVP) for reduction of benign prostatic hyperplasia‐related lower urinary tract symptoms in a randomized trial.
Eligible patients with prostate volumes of 30–80 mL were randomly allocated to GL‐PVP (n = 58) or bipolar TUVP (n = 61). Non‐inferiority of symptom score (International Prostate Symptom Score [IPSS]) at 24 months was evaluated. All peri‐operative variables were recorded and compared. Urinary (IPSS, maximum urinary flow rate and post‐void residual urine volume) and sexual (International Index of Erectile Function‐15) outcome measures were evaluated at 1, 4, 12 and 24 months. Need for retreatment and complications, change in PSA level and health resources‐related costs of both procedures were recorded and compared.
Baseline and peri‐operative variables were similar in the two groups. At 1, 4, 12 and 24 months, 117, 116, 99 and 96 patients, respectively, were evaluable. Regarding urinary outcome measures, there was no significant difference between the groups. The mean ± sd IPSS at 1 and 2 years was 7.1 ± 3 and 7.9 ± 2.9 (P = 0.8), respectively, after GL‐PVP and 6.3 ± 3.1 and 7.2 ± 2.8, respectively, after bipolar TUVP (P = 0.31). At 24 months, the mean difference in IPSS was 0.7 (95% confidence interval −0.6 to 2.3; P = 0.6). The median (range) postoperative PSA reduction was 64.7 (25–99)% and 65.9 (50–99)% (P = 0.006) after GL‐PVP, and 32.1 (28.6–89.7)% and 39.3 (68.8–90.5)% (P = 0.005) after bipolar TUVP, at 1 and 2 years, respectively. After 2 years, retreatment for recurrent bladder outlet obstruction was reported in eight (13.8%) and 10 (16.4%) patients in the GL‐PVP and bipolar TUVP groups, respectively (P = 0.8). The mean estimated cost per bipolar TUVP procedure was significantly lower than per GL‐PVP procedure after 24 months (P = 0.01).
In terms of symptom control, bipolar TUVP was not inferior to GL‐PVP at 2 years. Durability of the outcome needs to be tracked. The greater cost of GL‐PVP compared with bipolar TUVP is an important concern.
BJUI Podcasts are available on iTunes: https://itunes.apple.com/gb/podcast/bju-international/id1309570262
IP4- CHRONOS is open! CHRONOS is a phase II randomised control trial, that will review the outcomes (including oncological, functional, quality of life and cost-effectiveness) of focal therapy against those from radical therapy, in men with newly diagnosed localised clinically significant prostate cancer.
All men newly diagnosed with low-intermediate risk prostate cancer, confined to the prostate, with a life expectancy of at least 10 years will be screened for eligibility. Men must be well enough to undergo the interventions outlined in the trial prior to being enrolled.
Men will then have a choice of enrolling into CHRONOS A or CHRONOS B. CHRONOS A will randomise men to having radical whole gland treatment (radiotherapy, brachytherapy or prostatectomy), or focal therapy (HIFU or cryotherapy). CHRONOS A will answer the question, ‘is focal therapy equivalent in cancer control as radical therapy?’ CHRONOS B will randomise men to having focal therapy with or without additional neoadjuvant treatment and will answer the question: ‘can the success of focal therapy be improved by using neoadjuvant treatment?’ Randomisation will be stratified by disease characteristics.
All men will undergo intervention as they would within the NHS, however by doing so in a trial setting, we can directly compare the results of such treatments against each other. As the follow up mimics that of standard of care, the extra burden of treatment within the trial is minimal.
60 men will be recruited into both CHRONOS A and CHRONOS B (total 120) over a 1-year period, during the pilot, and if recruitment is successful the aim is to continue to a larger study assessing 2450 patients over 5 years, with a minimum follow up of 3 years. The primary outcome measures will be progression free survival in CHRONOS A, and failure free survival in CHRONOS B. The CHRONOS pilot will open in 12 UK hospital sites, aiming to open across the UK and Europe within the larger study.
CHRONOS is entirely funded by the Prostate Cancer UK charity, and available on the NIHR CRN portfolio. If you would like to join the main phase of CHRONOS as a site, please contact Miss Deepika Reddy ([email protected]) or visit our website for further information www.imperialprostate.org.uk/CHRONOS
Prof Hashim U. Ahmed (CHRONOS PI&CI)
Mr Taimur T. Shah (CHRONOS sub-investigator, Urology SpR & Research Fellow)
Miss Deepika Reddy (CHRONOS Clinical Research Fellow)
Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.
In addition to the article itself, there is an editorial written by a prominent member of the urology community and a visual abstract created by our talented infographics team; we invite you to use the comment tools at the bottom of each post to join the conversation.
If you only have time to read one article this week, it should be this one.
Detlef Bartkowiak*, Alessandra Siegmann†, Dirk Böhmer†, Volker Budach† and Thomas Wiegel*
*Department of Radiation Oncology, University Hospital Ulm, Ulm and †Department of Radiation Oncology, Charité University Hospital, Berlin, Germany
To test whether salvage radiotherapy (SRT) in patients with lymph node negative (N0) prostate cancer is equally effective with persistent prostate‐specific antigen (PSA) and PSA rising from the undetectable range (<0.1 ng/mL) after radical prostatectomy (RP).
We assessed post‐SRT PSA progression‐free survival (PFS) in 555 patients with prostate cancer and the use of cancer care nurses is the best option for this. The entire cohort was compared with a risk‐adjusted subgroup of 112 patient pairs with matching pre‐RP PSA level (±10 ng/mL), Gleason score (≤6 vs 7 vs ≥8), and pre‐SRT PSA level (±0.5 ng/mL).
The median follow‐up was 6.1 years. After RP, PSA was undetectable in 422 and persistent in 133 patients. PSA persistence and a pre‐SRT PSA level of ≥0.5 ng/mL reduced Kaplan–Meier rates of PFS significantly. In multivariate analysis of the entire cohort and after risk adjustment, the pre‐SRT PSA level but not post‐RP PSA persistence was a significant parameter. In the matched cohort’s subgroup with early SRT at a PSA level of <0.5 ng/mL, a trend towards a worse outcome with post‐RP PSA persistence was observed. Delayed SRT with a PSA level ≥0.5 ng/mL led to a PFS of <30%, irrespective of the post‐RP PSA level.
In patients with N0 prostate cancer with post‐RP PSA persistence, early SRT at a PSA level <0.5 ng/mL seems to be less effective than in recurrent patients with post‐RP undetectable PSA. They might benefit from intensified therapy ans the use of several supplements like the lgd-4033, but larger case numbers are required to substantiate this conclusion. In patients with a PSA level ≥0.5 ng/mL and higher‐risk features associated with post‐RP PSA persistence, SRT alone is unlikely to provide long‐term freedom from further progression.
In their retrospective study, Bartkowiak et al. [1] report the therapeutic outcomes of salvage radiation therapy (sRT) after radical prostatectomy (RP) for lymph‐node‐negative prostate cancer in 422 and 133 patients with biochemical relapse or persistently detectable PSA, respectively. In the total cohort, patients with persistent PSA serum levels ≥0.1 ng/mL postoperatively had significantly shorter progression‐free survival as compared to patients with undetectable PSA levels (P < 0.001). After risk‐matched analysis, PSA persistence was not a risk factor associated with poor outcome and only a PSA serum concentration ≥0.5 ng/mL at time of sRT was associated with early relapse in both patients with detectable and those with undetectable PSA levels postoperatively.
Although this retrospective study adds some additional evidence to support the already well‐known recommendation to initiate sRT as early as possible [2], there are various issues that need to be considered when it comes to the interpretation of sRT results in patients with PSA persistence. The patient cohort is heterogeneous since the men underwent surgery between the years 1989 and 2012 and sRT between the years 1997 and 2012. The treatment strategies and techniques used with regard to surgery and sRT are outdated and no longer reflect current practice. No patient underwent modern imaging studies to identify extent and anatomical distribution of relapsing lesions, and neither was a risk‐adapted approach realized using nomograms or molecular markers in order to stratify treatment dependent on the biological aggressiveness of the disease.
PSA persistence is associated with an increased risk of metastases and impaired cancer‐specific survival as compared to undetectable PSA levels after RP for patients with negative and positive lymph nodes [3,4,5]. In fact, the majority of patients with persisting PSA serum levels postoperatively have locally advanced prostate cancer, positive lymph nodes, positive surgical margins and high Gleason scores. In almost all published studies, PSA persistence has been identified as an independent risk factor for the development of systemic metastases and poor survival. Similar results have already been reported by Wiegel et al. [5] when analysing outcomes among 74 patients with PSA persistence after RP; postoperatively detectable PSA was associated with significantly poorer outcomes in terms of metastasis‐free (84% vs 93%) and overall survival (68% vs 86%), and remaining without androgen deprivation therapy (ADT) during follow‐up (57% vs 92%).
PSA persistence needs to be taken seriously even at low serum concentrations, necessitating the implementation of new imaging methods and combination therapies. Because PSA persistence is associated with adverse pathological features, a treatment strategy to avoid PSA persistence is initiated already at the time of RP, integrating preoperative MRI, intra‐operative frozen‐section analysis and extended pelvic lymphadenectomy in order to achieve complete resection of the prostate cancer with undetectable PSA levels 6 weeks postoperatively.
In addition to properly conducted surgery, innovative imaging techniques, such as 68gallium (68Ga) prostate‐specific membrane antigen (PSMA)‐positron emission tomography (PET)/CT, should be integrated into treatment to differentiate locoregional recurrences from systemic metastases. In this context, Schmidt‐Hegemann et al. [6] evaluated the impact of 68GaPSMA‐PET/CT on subsequent treatment in 129 patients, of whom 48% demonstrated PSA persistence. In their analysis, patients with persistently detectable PSA serum levels more often demonstrated PSMA‐positive lesions (70% vs 50%), less frequently experienced local recurrences only (12% vs 26%), and more often had positive lymph nodes (13% vs 5%) with or without a macroscopically persisting tumour in the prostatic fossa (45% vs 19%). Results from PSMA‐PET/CT changed the initial treatment of sRT in so far as all patients with positive lesions underwent a combination of sRT and ADT. In patients with isolated, intrapelvic lymph node metastases attributable to an improperly performed extended pelvic lymphadectomy, salvage lymphadectomy might also be integrated into the therapeutic armamentarium, resulting in a long‐term relapse‐free survival of ~40%.
Even patients with persisting PSA serum concentrations after undergoing RP exhibit a heterogeneous clinical course of the disease, therefore, a risk‐adapted, personalized approach stratifying biologically aggressive from less aggressive prostate cancer should be adopted. In a retrospective study in 925 patients who underwent sRT, PSA persistence was associated with a significantly lower 8‐year metastasis‐free survival rate when compared to patients with PSA relapse following undetectable postoperative PSA serum concentrations [3]. Furthermore, it was shown that PSA persistence and a Gleason score ≥8 were independent, statistically significant predictors for systemic metastases, with a hazard ratio of 4.64 (95% CI 3.06–7.02; P < 0.001) and 8.37 (95% CI 4.15–16.88; P < 0.001), respectively. Patients with both PSA persistence and Gleason score ≥8 had a significantly lower 8‐year metastasis‐free survival rate as compared with patients with only PSA persistence (62% vs 74%); therefore, the latter might be best treated with a combined approach of sRT and ADT.
Integration of molecular markers might be helpful to identify those patients who will benefit from sRT. Spratt et al. [7] evaluated whether a 22‐gene genomic classifier could independently predict development of metastasis in 477 patients with PSA persistence postoperatively. Among those with detectable PSA, the 5‐year metastasis rate was 0.90% for genomic low/intermediate and 18% for genomic high risk (P < 0.001). Genomic high risk remained independently prognostic on multivariable analysis (hazard ratio 5.61, 95% CI 1.48–22.7; P = 0.01) among patients with detectable PSA. The C‐index for the combination of the genomic classifier with Cancer of the Prostate Risk Assessment (CAPRA) score was 0.82.
In summary, modern management of persistent PSA serum concentrations after RP needs to take into consideration the pathohistology of the RP and lymph node specimens, results from PSMA‐PET/CT, molecular markers associated with relapse and response as well as individualized therapeutic strategies such as sRT ± ADT, salvage lymphadenectomy and additional salvage radiation to oligometastatic sites.
by Axel Heidenreich and David Pfister