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Re: Suture Techniques during Laparoscopic and Robot-Assisted Partial Nephrectomy

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Letter to the Editor

Suture Techniques during Laparoscopic and Robot-Assisted Partial Nephrectomy: A Systematic Review and Quantitative Synthesis of Peri-Operative Outcomes

Dear Sir,

We would like to congratulate the authors of this systematic review [1] highlighting the evolution of suture techniques for partial nephrectomy in the era of minimally invasive surgery. The authors note the “significant technical modification” for the replacement of intracorporeal free-hand knot tying with a sliding clip technique [2]. This technique has revolutionised the practice of PN and reduced the risk of the “cheese cutting effect” with the conventional suturing techniques. It is worth noting that this laparoscopic technique was first described by Agarwal et al in the BJUI in 2007 [3]. Indeed one of the authors of this SR also published on the robotic application of this technique in a publication in European Urology in 2009 (2), which also was remiss in referencing the original description of the technique by Agarwal et al., published 2 years prior.

This oversight aside, the authors should be commended for helping to frame the evolution of surgical techniques across minimally invasive approaches over time, with the ultimate goal of complete tumour excision, minimal complications and maximal functional preservation, since we’re using more technology now a days for advance study of medicine, like robots or CT scanners, although the cost of these CT scanners could be high, the value is worthy because they help a lot in the medicine area. While this paper’s title suggests a focus on suture techniques during surgery the authors concluding remarks do not address this focus. We believe suturing techniques will continue to evolve, and that there will be further technological, and technical innovation that will further improve outcomes for patients and will make more meaningful additions to the published literature in this field.

Brian D Kelly, Christophe Orye, Homi Zargar, Anthony J Costello and Dinesh Agarwal

Correspondence: Dinesh Agarwal, Urology Unit, Level 3 Centre, Infill Building, The Royal Melbourne Hospital, City Campus, Grattan Street, Parkville 3050 Victoria, Australia.
e-mail: [email protected]

 

References

  1. Bertolo, Riccardo et al. Suture Techniques during Laparoscopic and Robot-Assisted Partial Nephrectomy: A Systematic Review and Quantitative Synthesis of Peri-Operative Outcomes. BJU Int 2018;  123:923-46 doi:https://dx.doi.org/10.1111/bju.14537.
  2. Benway, Brian M et al. Robotic Partial Nephrectomy with Sliding-Clip Renorrhaphy: Technique and Outcomes. Eur Urol 2009; 55:592-9 doi:10.1016/j.eururo.2008.12.028.
  3. Agarwal, Dinesh et al. Modified Technique of Renal Defect Closure Following Laparoscopic Partial Nephrectomy. BJU Int 2007; 100:967-70 doi:10.1111/j.1464-410x.2007.07104.x.
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Re: Incidentally detected testicular lesions <10 mm in diameter: can orchidectomy be avoided?

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Letter to the Editor

Incidentally detected testicular lesions <10 mm in diameter: can orchidectomy be avoided?

Dear Sir,

We have read with great interest the paper “Incidentally detected testicular lesions <10 mm in diameter: can orchidectomy be avoided?” by Scandura et al. (1) in which only one third of such lesions turned out to be malignant and 100% of those <5 mm were benign. The authors call those patients who underwent orchidectomy for benign lesions “victims of modern imaging technology”.

With the widespread use of ultrasonography (US) of the scrotum, we see at this level what observed previously in other organs: thyroid (non-palpable nodules) (2), liver (unsuspected cysts and haemangiomas) (3), gallbladder (asymptomatic stones) (4), kidneys (simple renal cysts) (5). US is demonstrating the real prevalence of “lesions” in the testis. The problem is that, often, we do not know what they are, what their clinical relevance is, and how to manage these lesions.

Technical advances in US, such as elastography and contrast-enhanced studies, can help tissue characterization but often, unfortunately, these techniques are not able to differentiate between benign and malignant lesions (6). Further evaluation of the lesion with MR may be helpful to characterize a limited number of lesions only, such as lipomas, haematomas, and fibrous pseudotumours, but with reduced resolution in comparison to US (7).

The “scrotal and penile imaging working group” of the European Society of Urogenital Radiology (ESUR) has issued recommendations on how to approach a patient with small (<5 mm) testicular lesions (8). The document has suggested an avoidance of immediate orchidectomy, and to resort to active surveillance with US examination every three months in the first year and then annually. Surgery should be considered only for lesions that show increasing volume at follow-up.  Alternatively, testicular sparing surgery can be used, with removal of the lesion, frozen-section analysis of the specimen and decision on orchidectomy (or not) based on the results provided by the pathologist.

Close cooperation among different specialists is needed in this field. A multidisciplinary “testis unit” in which urologists, radiologists and pathologists work together on these patients and learn how to choose the best approach to each of them is the likely solution.

A patient who undergoes orchidectomy for an incidentally discovered small testicular nodule which turns out to be benign is not a “victim of modern imaging technology”. He is more likely the victim of our misunderstanding of the meaning of what technology shows us and the adherence to reactionary, outdated surgical dogma to the focal intra-testicular lesion.

Michele Bertolotto1, Paul S Sidhu2, Lorenzo E. Derchi3 

1Department of Radiology, University of Trieste, Italy

2Department of Radiology, King’s College Hospital, Denmark Hill, London, UK

3Department of Health Sciences (DISSAL), University of Genoa, Emergency Radiology, Ospedale Policlinico San Martino, Genoa, Italy

References

  1. Scandura G, Verrilli C, Protheroe A, et al. Incidentally detected testicular lesions <10 mm in diameter: can orchidectomy be avoided? BJU Int 2018; 121:575-582
  2. Tan GH, Gharib H. Thyroid incidentalomas: management approaches to nonpalpable nodules discoverend incidentally in thyroid imaging. Ann Int Med 1997; 126:226-231
  3. Kaltenbach T E-M, Engler P, Kratzer W, et al. Prevalence of benign focal liver lesions: ultrasound investigation of 45.319 hospital patients. Abdom Radiol 2016; 41:25-32
  4. Barbara L, Sama C, Morselli Labate AM, et al. A population study on the prevalence of gallstone disease: the Sirmione study. Hepatology 1987;7:913-917
  5. Ozveren B, Onganer E, Turkeri LN. Simple renal cysts: prevalence, associated risk factors and follow-up in a health screening color. Urol J 2016; 13:2569-2575
  6. Konstantatou E, Fang C, Romanos O, et al. Evaluation of intratesticular lesions with strain elastography using strain ratio and color map visual grading: differentiation of neoplastic and nonneoplastic lesions. J Ultrasound Med 2019; 38:223-232
  7. Tsili AC, Bertolotto M, Rocher L, et al. Sonographically indeterminate scrotal masses: how MRI helps in characterization. Diagn Interv Radiolo 2018; 24:225-236
  8. Rocher L, Ramchandani P, Belfield J, et al. Incidentally detected non-palpable testicular tumours in adults at scrotal ultrasonography: impact of radiological findings on management. Radiologic review and recommendations of the ESUR scrotal imaging subcommittee. Eur Radiol 2016; 26:2268-2278

 

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Re: “Super-mini percutaneous nephrolithotomy (SMP) versus retrograde intrarenal surgery for the treatment of 1-2 cm lower-pole renal calculi: an international multicentre randomized controlled trial”

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Letter to the Editor

Super-mini percutaneous nephrolithotomy (SMP) versus retrograde intrarenal surgery for the treatment of 1-2 cm lower-pole renal calculi: an international multicenter randomized controlled trial

Dear Sir,

We are interested to read the study by Zeng et al. [1] and appreciate the authors for their study showing that super-mini-percutaneous nephrolithotomy (SMP) was more effective than retrograde intrarenal surgery (RIRS) to treat 1-2 cm lower-pole renal calculi in terms of a better stone-free rate and lesser auxiliary rate. However, some issues still require clarification in this study.

The study validated that SMP was more effective than RIRS to treat 1-2 cm lower-pole renal calculi. However, the results should be explained with caution. As we known, pyelocaliceal anatomy seriously influences the performances of flexible ureteroscopy, while no obvious affection for SMP [2]. This parameter should be evaluated before patients were randomized into RIRS groups. Although there were no significant differences in characteristics of lower-pole spatial anatomical between the two groups, it would be more reasonable and reliable to compare the efficacy between SMP and RIRS, after excluding the patients with unfavorable pyelocaliceal anatomy such as an acute infundibulopelvic angle, or a long lower-pole calyx infundibulum.

The authors set a definition of stone-free status as no residual fragments of ≥0.3 cm on KUB and ultrasound at 1-day and on CT scan at 3-months after operation. We are curious to know how the authors managed when the results were different between KUB and ultrasound. As the primary endpoint was the stone-free rate at 3-months after surgery, we would like to know the size of the residual fragments in the 6.2% (5/80) of patients in SMP and 17.5% (14/80) in RIRS. Do they need another auxiliary procedure? All those information is important for drawing the final conclusion.

The study was an international multicentre, prospective, randomized, non-blinded controlled study, conducted at 10 academic medical centers in China, India, and Turkey. The authors said the two groups had similar baseline characteristics, but we would like to know if it was so for each center. If not, did it affect the final results when exclude those centers?

In conclusion, Zeng et al. made a laudable effort and have provided a level-1 evidence comparing the two modalities for treating 1-2 cm lower-pole renal calculi, but the authors’ conclusion should be taken with caution until more reasonable prospective studies with large sample size have been conducted. We look forward to the authors’ reply to clarify our queries.

 

Conflict of interest

The authors declare that they have no conflicts of interests.

 

Huiming Jiang1*, Nanhui Chen1

1Department of Urology, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, No.63, Huang Tang Road, Meizhou 514031, Guangdong, People’s Republic of China.

 

References

  1. Zeng G, Zhang T, Agrawal M et al. (2018) Super-mini percutaneous nephrolithotomy (SMP) vs retrograde intrarenal surgery for the treatment of 1-2 cm lower-pole renal calculi: an international multicentre randomised controlled trial. BJU international. 2018;122(6):1034-1040. doi: 10.1111/bju.14427
  2. Geavlete P, Multescu R, Geavlete B (2008) Influence of pyelocaliceal anatomy on the success of flexible ureteroscopic approach. Journal of endourology 22 (10):2235-2239. doi:10.1089/end.2008.9719

 

 

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Re: Does the introduction of prostate multiparametric MRI into the active surveillance protocol for localized PCa improve patient re-classification?

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Letter to the Editor

Does the introduction of prostate multiparametric magnetic resonance imaging into the active surveillance protocol for localized prostate cancer improve patient re-classification?

Dear Sir,

Recently Bryant and colleagues published an important series on multiparametric magnetic resonance imaging (mpMRI) in active surveillance (AS) for prostate cancer [1]. The work was deservedly highlighted as Paper of the Week for its potential impact on clinical practice. Meanwhile, it caught our attention that the authors – as many before them – use the term “significant prostate cancer” throughout their paper. We feel that this issue needs to be addressed and discussed further.

As most prostate cancers have an indolent course, the term “significant prostate cancer” must be reserved for cancers, which are potentially lethal [2]. From earlier studies, we know that this group of cancers are characterized by high tumor stages, high Gleason scores, and a high percentage of tumor involvement on biopsies. However, this knowledge is based on systematic prostate biopsies. Thus, findings on mpMRI targeted biopsies, including increase in Gleason grade group, number of positive cores, and maximum cancer core length, cannot readily be translated to the clinical setting of earlier times. Tumor grade and volume of the disease may simply be upgraded even with no change in the underlying cancers. Nevertheless, this is usually how such findings are used and the focus is mainly on moving patients from AS to active treatment.

The potential problems of this approach are illustrated in the results of Bryant et al., as 30% of the patient cohort is taken out of the AS program after a median time of only 1.55 years with mpMRI based findings as the most common cause. In previous publications, men have been able to stay on AS for considerably longer with limited consequences on metastasis free survival [3]. The issue is further highlighted by results from the ProtecT trial in which there was a median of about 4 years before 30% of the active monitoring group had gone on to active treatment, without this causing a significant increase in either overall survival or disease specific survival [4]. In addition, data from prostate cancer cohorts not treated with curative intent show us that even men with localized intermediate risk prostate cancer have a low risk of dying from prostate cancer [5]. Seen in this context, it is plausible that some cancers are falsely classified as “significant” cancers as a result of mpMRI. Indeed, Bryant and colleagues illustrate that men undergoing mpMRI have an increased risk of discontinuing AS which may result in increased over-treatment. The issue is further exacerbated by the tendency to treat increasingly older patients even though a survival benefit from active treatment is questionable in this group.

There is no doubt that mpMRI may provide important and valuable information and it is a massive leap forward that we might be able to identify occult high-grade cancers early. However, this new tool must be used with consideration and respect for the gaps in our knowledge. In that context, it is likely that current indications for AS can be expanded to include more favorable intermediate risk cancers when the diagnosis is made based on mpMRI targeted biopsies combined with systematic biopsies. In addition, mpMRI should be utilized to reduce the proportion of patients who opt for active treatment due to anxiety or the burden of multiple sets of systematic biopsies. Exploring these issues are crucial because staying on AS is not just about safely avoiding surgery or radiotherapy. Rather it is about avoiding or postponing highly prevalent and clinically significant functional side effects with considerable implications for quality of life. Thus, we want to underline that the use of mpMRI should not only be used to exclude patients from AS protocols but also in future protocols to include men in such programs.

 

Conflicts of interest: Mikkel Fode is Advisory Board member for Astellas Pharma A/S and has received honoraria as speaker from Astellas Pharma A/S and Ferring Pharmaceuticals. Peter B. Østergren has received honoraria as speaker from Astellas Pharma A/S, Ferring Pharmaceuticals and IPSEN. Dr. Østergren has received honoraria for consultancies from Astellas Pharma A/S and as Advisory Board member for IPSEN. Kasper D. Berg has no conflicts of interest to declare.

 

Mikkel Fode MD, PhD, FECSM*, Kasper Drimer Berg MD, PhD†**, Peter Busch Østergren* MD, PhD

*Department of Urology, Herlev and Gentofte Hospital, Herlev, Denmark, †Department of Urology, Regional Hospital West Jutland, Holstebro, Denmark, **Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

 

References

  1. Bryant RJ, Yang B, Philippou Y, Lam K, Obiakor M, Ayers J, et al. Does the introduction of prostate multiparametric magnetic resonance imaging into the active surveillance protocol for localized prostate cancer improve patient re-classification? BJU Int.; 2018;122(5):794–800.
  2. Popiolek M, Rider JR, Andren O, Andersson S-O, Holmberg L, Adami H-O, et al. Natural history of early, localized prostate cancer: a final report from three decades of follow-up. Eur Urol.; 2013;63(3):428–35.
  3. Bokhorst LP, Valdagni R, Rannikko A, Kakehi Y, Pickles T, Bangma CH, et al. A Decade of Active Surveillance in the PRIAS Study: An Update and Evaluation of the Criteria Used to Recommend a Switch to Active Treatment. Eur Urol.; 2016;70(6):954–60.
  4. Hamdy FC, Donovan JL, Lane JA, Mason M, Metcalfe C, Holding P, et al. 10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer. N Engl J Med.; 2016;375(15):1415–24.
  5. Rider JR, Sandin F, Andren O, Wiklund P, Hugosson J, Stattin P. Long-term outcomes among noncuratively treated men according to prostate cancer risk category in a nationwide, population-based study. Eur Urol.; 2013;63(1):88–96.

 

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Reply by the authors

We thank Dr Fode and colleagues for their correspondence regarding our recently published manuscript [1]. We wish to clarify some of the issues and comments they highlight. Regarding the term “significant prostate cancer”, we agree that this definition should be reserved for cancers that are potentially lethal. Historically, and currently, in the context of Active Surveillance (AS), these cancers are characterised by a higher tumour stage, increased number of positive biopsy cores and/or longer cancer length, and higher Gleason grade group compared to baseline findings, in the absence of routine clinical use of any potential molecular determinants of a lethal phenotype. The clinical question addressed in our recent manuscript was whether introducing multi-parametric magnetic resonance imaging (mpMRI) into our AS protocol for localised prostate cancer improved patient re-classification. We did not define “significant prostate cancer”, but rather focused on the drivers for men to abandon AS and receive active treatment. We agree that the use of this imaging adjunct may therefore lead to disease upgrading, even without a biological change in the underlying cancer per se, and hence our use of the term “re-classification”, rather than disease “progression”.

The results of the targeted (plus systematic) biopsy following the initial undertaking of mpMRI during AS likely accounts for much of the 30% of our cohort receiving radical treatment after a median time of 1.55 years, as our protocol had been to undertake that first mpMRI around one year after starting AS. The reported cohort of AS patients had not received a baseline pre-biopsy mpMRI, as this practice was introduced at our institution in 2016 [2], after these men had started AS. Hence, it is likely that the timing of men leaving AS to receive treatment was triggered by the first mpMRI as a follow-up measure and subsequent repeat targeted biopsies, rather than true biological disease progression. The use of indiscriminate repeat biopsies at pre-specified and arbitrary intervals during any AS protocol (as practiced historically before the availability of mpMRI) is likely to have driven men towards active treatment unnecessarily, and added to potential adverse effects of repeat biopsies on functional outcomes after radical prostatectomy [3].

With regards to the ProtecT study [4], men in the non-intervention arm received Active Monitoring (AM), rather than intensive AS. In ProtecT, men on AM did not receive regular imaging by mpMRI, nor did they receive repeat biopsies unless triggered by a suspicion of disease progression. This is very different from contemporary AS protocols. It is therefore inappropriate to draw parallels between AM in ProtecT and contemporary AS.

We agree that benefits of mpMRI in AS programs may be to reduce the proportion of patients who opt for active treatment due to anxiety, as well as decreasing the burden of multiple sets of unnecessary systematic biopsies.

The true definition of “clinically significant” prostate cancer is subject to much controversy, and many prostate cancers are classified inappropriately as “significant”. This depends on complex biological and molecular features of aggressive and lethal disease – yet to be defined by ongoing research – as well as competing co-morbidity. We agree entirely with Fode and colleagues that many men with localised intermediate-risk prostate cancer have a relatively low risk of dying from prostate cancer. This underpins the recommendation from the UK National Institute for Health and Care Excellence (NICE) that patients with low-volume low- and intermediate-risk localised prostate cancer may consider AS as a viable management option, re-iterated in its recently updated guidelines under consultation [5,6,7].

 

Richard J. Bryant*† , Prasanna Sooriakumaran†**, Freddie C. Hamdy*† and Simon F. Brewster*

*Department of Urology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK, †Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK, and **Department of Uro-Oncology, University College London Hospital NHS Foundation Trust, London, UK

 

References

  1. Bryant RJ, Yang B, Philippou Y, Lam K, Obiakor M, Ayers J, et al. Does the introduction of prostate multiparametric magnetic resonance imaging into the active surveillance protocol for localized prostate cancer improve patient re-classification? BJU Int.; 2018;122(5):794–800.
  2. Bryant RJ, Hobbs CP, Eyre KS, Davies LC, Sullivan ME, Shields W, et al. Comparison of prostate biopsy with or without pre-biopsy multi-parametric MRI in prostate cancer detection: an observational cohort study. J Urol. 2018. [Epub ahead of print]
  3. Sooriakumaran P, Calaway A, Sagalovich D, Roy S, Srivastava A, Joneja J, et al. The impact of multiple biopsies on outcomes of nerve-sparing robotic-assisted radical prostatectomy. Int J Impot Res. 2012;24(4):161-4.
  4. Hamdy FC, Donovan JL, Lane JA, Mason M, Metcalfe C, Holding P, et al. 10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer. N Engl J Med.; 2016;375(15):1415–24.
  5. National Institute for Health and Care Excellence. Prostate Cancer: Diagnosis and Management (CG175). National Institute for Clinical Excellence; 2014.
  6. Graham J, Kirkbride P, Cann K, Hasler E, Prettyjohns M. Prostate cancer: summary of updated NICE guidance. BMJ 2014; 348: f7524
  7. https://www.nice.org.uk/guidance/GID-NG10057/documents/evidence-review-7.

 

 

RE: National implementation of multi-parametric MRI for prostate cancer detection – recommendations from a UK consensus meeting

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Letter to the Editor

National implementation of multi-parametric magnetic resonance imaging for prostate cancer detection – recommendations from a UK consensus meeting [1]

Dear Sir,

Appaya et al report on an expert consensus meeting regarding the implementation of multi-parametric magnetic resonance imaging (mpMRI) for prostate cancer detection [1]. A key item related to ‘who can request an mpMRI’ for patients with suspicion of prostate cancer. The panel unanimously agreed that GPs should not be able to. This is perhaps unsurprising, given the panel was composed entirely of specialists. The authors did consider inviting a GP: however, their assumption was that other than for this question a GP would have little to add. We believe this was a critical omission, as improving access to diagnostic testing in primary care could improve prostate cancer diagnosis,  urology outpatient workloads, patient experiences, and outcomes.

The vast majority of cancer diagnoses, including prostate, occur in symptomatic patients presenting to primary care [2]. GPs already have direct access to diagnostic testing for several other cancer types in the NHS – all endorsed by NICE guidance – including gastroscopy, colonoscopy, flexible sigmoidoscopy, MRI head, ultrasound, and CT abdomen. Each can be requested in primary care, with GPs retaining clinical responsibility for the investigation findings [3].

An oft-raised concern with GP direct access to diagnostic tests is that it will lead to inappropriate referrals. However, a recent systematic review of direct access cancer testing in primary care found no significant difference in pooled cancer conversion rate between GP and specialist requests (except for gastroscopy) and no significant difference in the appropriateness of referrals. Time from referral to testing was shorter with GP direct access testing and patient satisfaction was high [4].

If implementation of pre-biopsy mpMRI truly does reduce the need for biopsy in 27% of men, as suggested from the PROMIS [5] and PRECISION [6] trials, then direct access testing in primary care could significantly reduce referrals for suspected prostate cancer. At a time of limited NHS resources and more ambitious targets for cancer diagnosis and treatment times, this could ease the pressure on Urology departments across the UK.

There are several unanswered questions with regard to the optimal use of pre-biopsy mpMRI: for example, which men to test, how to safely follow-up mpMRI-negative patients, and MRI capacity. Including GPs in these discussions would not just be courteous: it may find better answers.

Dr Samuel Merriel1, Dr Fiona Walter2, Prof Willie Hamilton3

1 Clinical Research Fellow, University of Exeter

2 Principle Researcher in Primary Care Cancer Research, University of Cambridge

3 Professor of Primary Care Diagnostics, University of Exeter

References

  1. Appayya MB, Adshead J, Ahmed HU, Allen C, Bainbridge A, Barrett T, et al. National implementation of multi-parametric magnetic resonance imaging for prostate cancer detection – recommendations from a UK consensus meeting. BJU Int. 2018;122(1):13–25.
  2. Emery JD, Shaw K, Williams B. The role of primary care in early detection and follow-up of cancer. Nat Rev Clin Oncol. 2014;11:38–48.
  3. National Collaborating Centre for Cancer. Suspected cancer [Internet]. NICE. London; 2015.
  4. Smith CF, Tompson AC, Jones N, Brewin J, Spencer EA, Bankhead CR, et al. Direct access cancer testing in primary care: a systematic review of use and clinical outcomes. Br J Gen Pract. 2018;(August):1–10.
  5. Ahmed HU, El-Shater Bosaily A, Brown LC, Gabe R, Kaplan R, Parmar MK, et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet [Internet]. 2017;389(10071):815–22.
  6. Kasivisvanathan V, Rannikko AS, Borghi M, Panebianco V, Mynderse LA, Vaarala MH, et al. MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis. N Engl J Med [Internet]. 2018.
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Reply by the authors

I thank Dr Samuel Merriel and Dr Fiona Walter for writing in about the role of the GP in requesting prostate MRI studies. Indeed, we reported that our consensus panel unanimously agreed that GPs should not be requesting prostate MRI studies [1]. Their letter in follow-up of this offers an opportunity to explain further this recommendation.

We adopted a UCL-RAND based methodology to conduct the consensus meeting. Whilst we would have liked to have broader representation on the panel, one of the key metrics necessitates that a minimum proportion of participants be able to answer a particular question for that question to be valid. Further broadening of the panel risked delivery of this.

Nonetheless, we agree that GP representation in designing and implementing healthcare is invaluable and should not be ignored and could have all of the benefits for prostate cancer diagnostics that are pointed out by Dr Merriel and Dr Walter.

To clarify the consensus panels discussion on this topic; the panel felt that within the current climate there remained many areas that needed standardisation and improvement if we are to realise the benefits highlighted in PROMIS [2] and PRECISION [3] e.g. diagnostic quality of scans, training of radiologists to report scans all the way through to a consensus from urologists of how to manage patients with a specific scan result.  The panel did not believe that GPs were incapable of managing direct referral services for prostate MRI, only that this needed to be introduced in a controlled fashion if we were to be successful in implementing multi-parametric MRI whilst maintaining its performance and value. The panel felt that direct GP referral should therefore be re-discussed once mechanisms to maintain scan quality and standards of reporting were realised across the UK.

Indeed, GPs should be included in the discussion of which men to test, how to follow-up mp-MRI negative patients and those related to MRI capacity – all of these assume that one is looking at a test that is correctly set-up and reported to a specific standard. Perhaps a consensus on management of patients amongst urologists and primary care physicians is a warranted next step.

Shonit Punwani1

1Centre for Medical Imaging, University College London, UK.

References

  1. Appayya MB, Adshead J, Ahmed HU et al. National implementation of multi-parametric magnetic resonance imaging for prostate cancer detection – recommendations from a UK consensus meeting. BJU Int 2018; 122:13-25.
  2. Ahmed HU, El-Shater Bosaily A, Brown LC, Gabe R, Kaplan R, Parmar MK, et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet [Internet]. 2017;389(10071):815–22.
  3. Kasivisvanathan V, Rannikko AS, Borghi M, Panebianco V, Mynderse LA, Vaarala MH, et al. MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis. N Engl J Med [Internet]. 2018.

 

 

RE: National implementation of multi-parametric MRI for prostate cancer detection – recommendations from a UK consensus meeting

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Letter to the Editor

National implementation of multi-parametric magnetic resonance imaging for prostate cancer detection – recommendations from a UK consensus meeting [1]

Dear Sir,

We congratulate the authors for their efforts in standardising prostate mpMRI. However, we are concerned that the consensus as reported may place substantial pressure on the diagnostic pathway in a rapidly evolving field. Most departments in the West of Scotland and the UK are striving to offer a routine pre-biopsy MRI service, witnessing doubling of the demand on scanning and radiologist time [2], aggravating the nationwide shortage of radiologists [3].

A standard reporting system is vital to the consistent implementation of diagnostic pathways. PI-RADS version 2 focuses on the standardisation of reading, setting out where and when to use each sequence, and has been widely implemented [4]. This, however, has taken time and its learning curve is ongoing within local hospitals [5]. Its main advantage over a clinico-radiological Likert impression is the reduced flexibility of interpretation of radiological parameters, giving those gaining experience in the field a clear set of definitions to work to. We are concerned that enforcing a second system so quickly will discourage radiologists during their learning curves. The panel is entirely correct in stating that even with the use of Likert system, the reporting will be influenced by PI-RADS criteria. While the urology and uro-radiology communities have widely embraced PI-RAD reporting, official switch to Likert reporting may introduce unnecessary reporting subjectivity before individual radiologists are fully experienced with the use of PI-RADS. Furthermore, with the expectation of PI-RADS v3 in the near future, it may be better to adopt PI-RADS v2 now, and compare PI-RADS v3 and Likert system in due course.

The panel describes dynamic contrast enhancement (DCE) as essential component and we agree that mpMRI incorporating the use of contrast is well established, with particular impact on the distinction between PIRADS 3 and 4 lesions. However, a short 9 minute biparameteric MR protocol was as good as a longer and more elaborate protocol using DCE in detecting clinically significant prostate cancer [6]. In NHS Greater Glasgow and Clyde (NHSGGC), we adopted a pragmatic approach, selecting patients for whom contrast may be particularly informative, i.e. those with hip replacement surgery and those who had previous negative biopsies. A contrast MRI prostate scan takes at least 10 minutes longer, and requires nominated radiologist supervision, reducing the overall capacity by 20%. In a 12 month period (2017-2018), 2,333 diagnostic MR prostate scans (20% with contrast) were performed within NHSGGC. For full adoption of contrast prostate MR, it will be necessary to increase the imaging capacity by ~100 supervised imaging lists per annum. Pharmacokinetic modelled DCE parameters (and not visually inspected start of enhancement) have the greatest potential to detect aggressive disease [7,8]. However this approach is currently not deemed feasible for widespread UK use, due to the lack of suitable standardized software.

In summary, we welcome the consensus recommendations for a unified prostate cancer imaging diagnostic strategy, but propose a pragmatic evolving approach that is sympathetic to the constraints of local and regional resources, both in terms of imaging capacity and uro-radiology reporting expertise.

Elizabeth Day1, Amit Patel2, John Morrison2, Thomas Hambrock3, Hing Y Leung1,4

1 Department of Urology, NHS Greater Glasgow and Clyde, Glasgow, G12 0XH

2 Department of Radiology, NHS Greater Glasgow and Clyde, Glasgow, G12 0XH

3 Department of Radiology, The Christie NHS Foundation Trust, Manchester M20 4BX

4 CRUK Beatson Institute for Cancer Research, Glasgow G61 1BD

 

References

  1. Appayya MB, Adshead J, Ahmed HU et al. National implementation of multi-parametric magnetic resonance imaging for prostate cancer detection – recommendations from a UK consensus meeting. BJU Int 2018; 122:13-25.
  2. Day E, Nalagatla S, Shin JS et al. Triaging patients to primary biopsy or prostate MRI based on digital rectal examination improves the detection rate of TRUS biopsy and avoids unnecessary biopsies. JCU 2018.
  3. The Royal College of Radiologists. Scottish patients at risk from radiologist shortages. 2018.
  4. Padhani AR, Weinreb J, Rosenkrantz AB et al. Prostate Imaging-Reporting and Data System Steering Committee: PI-RADS v2 Status Update and Future Directions. Eur Urol 2018.
  5. Hansen NL, Koo BC, Gallagher FA et al. Comparison of initial and tertiary centre second opinion reads of multiparametric magnetic resonance imaging of the prostate prior to repeat biopsy. Eur Radiol 2017; 27:2259-2266.
  6. Kuhl CK, Bruhn R, Krämer N et al. Abbreviated Biparametric Prostate MR Imaging in Men with Elevated Prostate-specific Antigen. Radiology 2017; 285:493-505.
  7. Vos EK, Litjens GJ, Kobus T et al. Assessment of prostate cancer aggressiveness using dynamic contrast-enhanced magnetic resonance imaging at 3 T. Eur Urol 2013; 64:448-55.
  8. Hambrock T, Vos P, Hulsbergen-van de Kaa C et al. Prostate cancer: computer-aided diagnosis with multiparametric 3-T MR imaging–effect on observer performance. Radiology 2013; 266:521-30
Read the article

Reply by the authors

I read with great interest the letter composed by Day et al regarding our article: National implementation of multi-parametric magnetic resonance imaging for prostate cancer detection – recommendations from a UK consensus meeting (Appayya et al [1]).

The authors of the letter highlight several important points that were indeed discussed in detail at the consensus meeting.

The first being the pressure on diagnostic services that is expected to result from the implementation of a strategy adopting multi-parametric MRI prior to biopsy. We concur that there is a real risk that without additional funding and the specific training of specialist radiologists in prostate MRI, our aspirations to implement pre-biopsy MR will meet limited success. The consensus panel did agree that this remains an area where national support and prioritisation will be a key driver of success or failure.

The second point raised by Day et al was in regard to recommendation for the use of Likert verses PI-RADS version 2 reporting systems. This again was a well debated item at the consensus meeting. To clarify the consensus discussion, the panel felt that the PI-RADS v2 system was a good system to use when training to report prostate MRI, specifically as it has a very rigid set of definitions. Indeed, the intention of the panel in recommending Likert reporting was not to disregard the PI-RADS system, but to highlight that when sufficiently experienced we also use other factors in scoring that were not as yet incorporated into PI-RADS v2. Indeed, many experienced radiologists knowingly/unknowingly do not adhere to strict PI-RADS v2 scoring. For example, PI-RADS v2 recommends that clinical details (including PSA) should not influence interpretation yet it is almost ubiquitous that we report in light of the PSA and are now recommending PSA density measures to help us guide practice. Furthermore, many centres in the UK do not perform DCE MRI, yet report score as a PI-RADS v2– although DCE MRI as Day et al point out is a key component of the PI-RADS v2 scoring system. Any reports produced for patients that have had previous treatment cannot be scored by PI-RADS v2 criteria, yet there are ongoing examples of radiologists stating a PI-RADS v2 score within such reports.

In reality, Day et al are correct in pointing out that PI-RADS v3 may indeed resolve many of these issues.  PI-RADS v3 was not as far developed when the consensus meeting took place.

With regard to a bi-parametric verses multi-parametric approach; I would agree that most significant tumours will be detected with a bi-parametric MRI and that it will be a small minority that would benefit from DCE MRI. The difficulty to date has been that DCE MRI applications are very varied across studies and have generally concentrated on the use of pharmacokinetic parameters – which has limited studies looking at the value of DCE-MRI. Indeed, such protocols are difficult to themselves apply. The panel felt that a high resolution short DCE protocol that lasted 3 minutes could be implemented with visual inspection of the early arterial phase image for the detection of early enhancement indicative tumour. They also acknowledged that further research is required to establish the benefits of DCE MRI.

I would like to thank Day et al for their letter, as it is important to highlight these areas from the consensus paper in order (i) to recognise where national support is required, (ii) to help clarify any areas which more detailed description could not be provided within the paper, and (iii) to continue to recognise areas where research and further technique refinement is required.

Shonit Punwani1

1Centre for Medical Imaging, University College London, UK.

References

  1. Appayya MB, Adshead J, Ahmed HU et al. National implementation of multi-parametric magnetic resonance imaging for prostate cancer detection – recommendations from a UK consensus meeting. BJU Int 2018; 122:13-25.

 

 

Meta-analysis of HIV-acquisition studies incomplete and unstable

/by

Letter to the Editor

Re: Male Circumcision for the Prevention of HIV Acquisition: A Meta-Analysis

Sir,

The authors of a recent meta-analysis[1] of studies into male circumcision and HIV describe their findings as “compelling.” We disagree. They reported a remarkably high degree of inconsistency with 97% of variation across studies due to heterogeneity rather than chance (an astounding, rarely seen, level of heterogeneity). Using recently described methods[2], 28.57% of the studies would need to have been excluded to bring I2 below the 50% threshold (considered high) and 32.65% excluded to bring I2 below the 25% threshold considered acceptable (well above the expected 99th percentiles of 22% and 32%, respectively). Similarly, 65.51% and 65.93% of the total number of participants needed to be excluded to reach the 50% and 25% thresholds (above the 99th percentiles of 25% and 48%, respectively). Given this excessive between-study heterogeneity, Sharma et al. should have refrained from reporting summary estimates[3].

The authors half-heartedly attempted to explain the heterogeneity failing to recognise that both the risk profile and circumcision prevalence of the study population are significant factors[4], and also failing to acknowledge the sizeable percentage of iatrogenically transmitted HIV infections[5].

The authors excluded approximately half of the published studies that met their inclusion criteria[4]. Excluding studies that focused only on MSM, which have a distinctly different risk profile, we calculate the included studies as significantly more likely to report a greater treatment effect (random-effect summary odds ratio (circumcised versus intact) of (0.44, 95%CI=0.36-0.59) than the excluded studies (0.66, 95%CI=0.56-0.78) − (change in ln(OR)=0.35, 95%CI=0.07-0.65, t=2.44, p=0.016).

In assessing publication bias, the authors provided a funnel graph, declaring that the data plots “appear to be evenly distributed about the mean effect size, suggesting an absence of publication bias,” without applying any routine statistical tests. Four of six commonly used measures[6] exhibited significant publication bias.

The results of the randomised clinical trials (RCTs) have been noted as being “remarkably similar”[7]  − the probability of the results of these trials being so tightly clustered is only 0.03[8]. Can the 0% I2 reported in the meta-analysis of the RCTs be interpreted as indicating no appreciable variability between the studies? This certainly arouses suspicion of prior coordination: as Ioannidis noted, “At the extreme, fraud can cause perfect replication”[9].

The large sample size RCTs allowed small numerical differences to have an exaggerated impact on p-values. The Fragility Index (FI) (number of times one patient with the relevant finding is subtracted from one group and added to another group before the results are no longer significant)[10] for the three clinical trials was 4, 5, and 6, respectively, with an FI of ≥ 8 being common, and an FI of ≤ 3 being suspect.  Early discontinuance of these fragile studies with an absolute risk reduction between 0.8% and 1.9% was an artifact of being overpowered.

Given the effectiveness of condoms[11], the lack of consistent findings on national levels[12], the methodologically flawed RCTs[13], the lack of translational research, and the impressive potential uptake and effectiveness of pre-exposure prophylaxis[14], circumcision as an intervention to prevent HIV infection should be treated with greater scepticism.

Robert S. Van Howe1, MD, FAAP, and Gregory J. Boyle2, PhD, DSc, FAPS

1College of Medicine, Central Michigan University , Saginaw , MI , USA

2University of Melbourne, Parkville, VIC 3010, Australia

 

Read the article

References

  1. Sharma SC, Raison N, Khan S, Shabbir M, Dasgupta P, Ahmed K. Male circumcision for the prevention of human immunodeficiency virus (HIV) acquisition: a meta-analysis. BJU Int 2018; 121:515-26. doi:10.1111/bju.14102
  2. Patsopoulos NA, Evangelou E, Ioannidis JPA. Sensitivity of between-study heterogeneity in meta-analysis: proposed metrics and empirical evaluation. Int J Epidemiol 2008; 37: 1148-57. doi:10.1093/ije/dyn065
  3. Mueller M, D’Addario M, Egger M, et al. Methods to systematically review and meta-analyse observational studies: a systematic scoping review of recommendations. BMC Med Res Methodol 2018; 18: 44.
  4. Van Howe RS. Circumcision as a primary HIV preventive: extrapolating from the available data. Glob Public Health 2015; 10: 607-25.
  5. Gisselquist D, Pottarat JJ, Brody S, Vachon F. Let it be sexual: how health care transmission of AIDS in Africa was ignored. Int J STD AIDS 2003; 14: 148-61.
  6. Macaskill P, Walter SD, Irwig L. A comparison of methods to detect publication bias in meta-analysis. Statist Med 2001; 20: 641-54.
  7. Sansom SL, Prabhu VS, Hutchinson AB, et al. Cost-effectiveness of newborn circumcision in reducing lifetime HIV risk among U.S. males. PLoS One 2010; 5(1): e8723.
  8. Van Howe RS. “Math is your friend: a consumer’s primer to understanding epidemiology.” Genital Autonomy 2014: Thirteenth International Symposium on Genital Autonomy and Children’s Rights. Boulder, Colorado. July 24, 2014.
  9. Ioannidis JP. Scientific inbreeding and same-team replication: type D personality as an example. J Psychosom Res 2012; 73: 408–10.
  10. Walsh M, Srinathan SK, McAuley DF, et al. The statistical significance of randomized controlled trial results is frequently fragile: a case for a Fragility Index. J Clin Epidemiol 2014; 67: 622-8.
  11. de Vincenzi I. A longitudinal study of human immunodeficiency virus transmission by heterosexual partners. European Study Group on Heterosexual Transmission of HIV. N Engl J Med 1994; 331: 341-6.
  12. Garenne M. Long-term population effect of male circumcision in generalised HIV epidemics in sub-Saharan Africa. Afr J AIDS Res 2008; 7: 1-8.
  13. Boyle GJ, Hill G. Sub-Saharan African randomised clinical trials into male circumcision and HIV transmission: methodological, ethical and legal concerns. J Law Med 2011; 19: 316-34.
  14. Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med 2012; 367(5): 399-410.

 

 

Re: Millin’s prostatectomy in the era of ‘Getting It Right First Time’ and Montgomery: exploring variation in clinical practice and consent

/1 Comment/by

Letter to the Editor

Millin’s prostatectomy in the era of ‘Get it Right First Time’ and Montgomery: exploring variation in clinical practice and consent.

We read with interest the comment in last months BJUI where it was suggested that the Millin retropubic simple prostatectomy for BPH should be confined to history in part because of the Montgomery ruling and the GIRFT programme [1]. GIRFT was designed to identify variations and raise standards of care. The urology report has since been published (it was not available when the original article was written) and Simon Harrison and his team should be congratulated for providing an excellent review of the current state of urology in the UK and identifying recommendations to improve patient care [2]. As surgeons we are acutely aware how the Montgomery ruling has shifted the test for appropriate consent from the “Bolam principle” to a patient orientated process. It is no longer for us to deem what information is relevant to inform the patient and all risks/benefits/alternatives must be outlined. We should all use a detailed, patient-centred, longitudinal approach to consent supplemented with BAUS information leaflets and other resources.

Where we disagree with the authors is to suggest that both of these key events (GIRFT and Montgomery) can be interpreted as justification for not performing a highly effective operation with excellent outcomes. Terence Millin described the transcapsular retropubic simple prostatectomy in 1945 and it revolutionised the management of men with BPH. There are few other procedures that have survived since their inception over 70 years ago in the same form [3] and it remains an established treatment for large glands in European, British and American urological guidelines respectively. More recently the robotic platform has been utilised to perform the technique, although more frequently a transvesical approach is deployed. When performed by well-trained surgeons it remains a procedure that yields very high patient satisfaction and low complication rates. Whilst accepting the cost implications of the slight increased length of stay the authors have failed to discuss the hidden costs of consumables, increased theatre time and further treatments that may be required for the transurethral enucleation procedures.

HES data shows that Millin prostatectomy is not a commonly performed operation. This reflects the fact that massively enlarged prostates are not as common as in the past, partly due to the widespread use of medical therapy and earlier referrals. However, the management of the extreme end of the enlarged benign prostate will always be challenging and we feel that there remains a need to have surgeons with the necessary skills to perform this procedure in the appropriately selected and consented patient. The largest adenoma enucleated by the authors is 980cc (GW) and we would suggest that this would represent a challenge for any transurethral approach. Indeed, the previous Editor of this journal commented in 2008 “some have said that the era of the Millin prostatectomy is over. I very much disagree with this and would not like to see the demise of such a satisfying surgical procedure, with excellent outcome for the patient” [4].

Andrew Chetwood1, Pravin Menezes2, Charles Coker3, Graham Watson4

1Frimley Health NHS Foundation Trust

2Kingston Hospital NHS Trust

3Brighton and Sussex University Hospitals NHS Trust

4East Sussex Hospitals NHS trust

References

  1. Millin’s prostatectomy in the era of ‘getting it Right First Time’ and Montgomery: exploring variation in clinical practice and consent. Malthouse T, Mistry K, Agrawal S. BJU Int 2018;122:171-172
  2. gettingitrightfirsttime.co.uk
  3. Retropubic prostatectomy; a new extravesical technique; report of 20 cases. Millin Lancet. 1945 Dec 1;2(6380):693-6.
  4. Surgery Illustrated – Millin Retropubic Prostatectomy. Fitzpatrick J, BJU Int 2008;102:906-916
Read the article

Reply by the authors

We wholeheartedly agree that the Millin’s is indeed a ‘satisfying surgical procedure, with excellent outcomes for the patient’ and it is not a procedure we would voluntarily relinquish. However as surgeons we should bear in mind the fundamental principles of ‘primum non nocere’ and need to put patient safety above our own wishes to perform a specific operation.  There have been several technological advances since 2008, with HOLEP at the forefront of BPE surgery for large volume glands showing safer and equally effective outcomes.  Indeed Terence Millen was a proponent of transurethral techniques developing his own Millin’s resectoscope, with the retropubic approach only evolving due to a lack of equipment after the world war. He may well have been the first to innovate.

Our article was designed to stimulate a debate around consent, safety, and cost effectiveness in our whole practice. However the principles outlined within GIRFT ideology and the current medicolegal world we live in, remain.   Consent for a Millin’s is clearly an issue with the need to specifically discuss (and document) alternatives including HOLEP, with evidence clearly showing improved safety, lower morbidity and length of stay. Additionally the majority of NHS trusts, have a centre within their region delivering this service and as such not offering HOLEP would not justify performing a Millin’s. Whilst we accept that newer minimally invasive techniques (robotic/laparoscopic with similar safety profiles) also exist and could be retained for the larger glands, we suspect the majority of open retropubic prostatectomies are not for 980cc volume prostates.

Finally, we would argue the fact that HES data shows the Millin’s to be a low volume procedure suggesting many have already changed practice. When considering costs towards consumables, these are incorporated and not in addition to tariffs paid to organisations. As tax paying members of the public and as clinicians we have a responsibility to use our funding and resources wisely. We believe that the literature would benefit from a modern-day case series to better inform this debate. Perhaps we need to define a volumetric cut off above which a retropubic or minimally invasive technique would be justifiable or cost effective?

Sachin Agrawal and Theo Malthouse

Ashford & St Peters NHS Foundation Trust

 

Re: Use of 5α-reductase inhibitors for BPH and risk of high-grade PCa: A French population-based study

/by

Letter to the Editor

Re: Use of 5α-reductase inhibitors for benign prostate hypertrophy and risk of high-grade prostate cancer: A French population-based study

Sir,

We read with interest the article entitled “Use of 5α-reductase inhibitors for benign prostate hypertrophy and risk of high-grade prostate cancer: A French population-based study” by Scailteux et al. [1]. We appreciate that patients should be informed about the high-grade disease that can develop in patients treated with 5-alpha reductase inhibitor for longer than 2 years.

However, we do not think that the use of the “benign prostatic hypertrophy” phrase, which has been used in nine places, is not correct when the histopathology of the disease is considered. Hypertrophy refers to an increase in cell size, while hyperplasia refers to an increase in cell number. For many years, physicians believed that this condition was caused by an increase in the size of certain cells in the prostate gland. However, studies and histopathological evaluations have shown that this is not a hypertrophy but hyperplasia with new dyes and techniques [2]. “Benign Prostate Hyperplasia” (BPH) is a histopathologically correct expression of benign prostatic enlargement that causes symptoms of lower urinary tract in men. Because the proliferation of stromal and glandular elements is involved in the histopathology of BPH.

When the references made using “hypertrophy” in the article were examined, it was seen that “hypertrophy” was not used in the studies of McConnell et al., and “hyperplasia” was used in both of the articles [3,4]. When the available literature on BPH was searched, it was observed that “hyperplasia” was used and abandonment of the term “hypertrophy” was observed.

As a result, we aimed to warn the editor not to make a clear terminology error in the British Journal of Urology International (BJUI), a respected journal in the field of urology.

Fatih Özkaya, Yılmaz Aksoy and Azam Demirel

Ataturk University Medical Faculty, Department of Urology, Erzurum, Turkey

Read the article

 

References

  1. Scailteux, L.M. et al. Use of 5alpha-reductase inhibitors for benign prostate hypertrophy and risk of high-grade prostate cancer: A French population-based study. BJU Int, 2018.
  2. Vinay Kumar, Abul K. Abbas and Jon C. Aster Male Genital System and Lower Urinary Tract. Robbins Basic Pathology Tenth ed.,2018, p.691-712
  3. McConnell, J.D. et al. The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. Finasteride Long-Term Efficacy and Safety Study Group. N Engl J Med, 1998. 338(9): p. 557-63.
  4. McConnell, J.D. et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med, 2003. 349(25): p. 2387-98.

 

Re: Efficacy and safety of PAE for BPH: an observational study and propensity-matched comparison with TUR of the prostate (the UK- ROPE study)

/by

Letter to the Editor

Efficacy and safety of prostate artery embolization for benign prostatic hyperplasia: an observational study and propensity-matched comparison with transurethral resection of the prostate (the UK- ROPE study)

Sir,

We read the manuscript by Ray and colleagues and congratulate the authors for the effort spent on this remarkable work. To date, this is the first large multicentre study to assess and compare the efficacy and safety of prostate artery embolization (PAE) for lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) with transurethral resection of the prostate (TURP). We have, however, some concerns regarding the interpretation and reporting of the study that warrant further clarification.

  • It was suggested that the PAE-related learning curve ranges from 10-20 cases. However, even with training and proctorship, the number of PAE each centre had performed to participate in the UK-ROPE Registry was not mentioned. It would be interesting to see a comparison of outcomes between PAE patients who had their procedures performed before and after the learning curve.
  • Unfortunately, due to the large number of centres in UK it was not possible to have a homogenous technique used in the PAE arm. Even considering that the PErFecTED was not used, each centre was allowed to use their own embolization technique.
  • Another technical issue concerns the use of cone-beam CT (CBCT) during the procedures. It is not clear whether CBCT was available and used in every case. For example, it was not mentioned whether penile ulcers were related to embolic agent’s reflux or to anastomoses that were not observed because CBCT was not available or was not used during PAE. All of these issues could be considered bias, however, it has been proven that clinical and imaging success can be achieved with different techniques.
  • Unfortunately, prostate volume measurement data were not available for TURP cases. This information could be important and supportive of the use of TURP, since men are very concerned about prostate volume before and after any therapy.
  • The estimated reported operation rate on and off the 12-month follow-up period was 19.9%. Cases of unilateral embolization, small prostate volume and median lobe enlargement were reported. However, the significance of small prostate volume was not defined, the grade of the median lobe enlargement, as well as if some patients had hypocontractile bladder rather than LUTS. Urodynamic studies might have a key role in this type of evaluation.
  • We understand that transient haematospermia and haematuria should be considered as side effects instead of complications, which could be added to a mail-based questionnaire system used to collect data in the Registry.

The pathophysiology of PAE is probably related to ischemia in the transitional zone of the prostate followed by coagulative necrosis. How was retrograde ejaculation (24.1%) diagnosed in the PAE group? Could it be due to a reduction in ejaculation volume resultant of prostatic tissue death after embolization? Some men stated they had been experiencing retrograde ejaculation prior to PAE due to medication. It seems that ejaculatory status was not captured at baseline. Future investigators should consider the importance of collecting these data preprocedure.

Francisco Cesar Carnevale MD PhD, Andre Moreira de Assis MD and Airton Mota Moreira MD PhD.

Department of Radiology, University of Sao Paulo, Sao Paulo, Brazil.

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Reply by the authors

We thank Carnevale and colleagues for their comments on our study. Regarding the PAE-related learning curve, these data are available and will be published separately. Procedural and screening times and therefore overall radiation dose reduced with increasing experience but there was very little difference in outcome measures in keeping with PAE being a robust technique in many centres and not just the well-known centres of excellence.

Four of the centres were trained and proctored by the Lisbon group and the remaining centres were trained by the University Hospital Southampton IRs using the same technique. The details of catheter and microcatheters used as well as the size and nature of the embolic particles are being published in a subsequent paper. Micro catheters of 2.4Fr and smaller were used in all cases at all centres. The majority of cases were embolized with either particulate PVA (Cook Medical or Boston Scientific) or spherical microspheres (Celonova/Boston Scientific). Cone beam CT was available in almost all centres and was used on the majority of cases. These data are available and are being collated for subsequent publication.

The study protocol and budget allowed normal practice for TURP patients. These did not therefore get formal Urodynamics nor post-surgical imaging and prostate volume measurements. While prostate volume was not formally measured for TURP we recorded resected weights which give some idea of gland volume, though not a reliable measure.

Unilateral embolization, small prostate volume and median lobe enlargement are important co-variates which are being analyzed and will be submitted for publication shortly. All patients having PAE had confirmed obstruction on UDS so hypocontractile bladders were excluded.

We agree that transient haematospermia and haematuria should be considered as side effects instead of complications, and could be added to a mail-based questionnaire system used to collect data in the Registry and we thank Carnevale and colleagues for pointing this out.

Baseline dry or retrograde ejaculation is common in marked prostatic enlargement being treated by alpha blockers such as Tamsulosin. It is a weakness of this study that we did not capture ejaculatory status at baseline. This will be answered in subsequent clinical studies derived from the UK-ROPE dataset.

All of these technical issues were not controlled in our pragmatic study, however, as Carnevale and colleagues note, the study has shown that clinical and imaging success can be achieved with different techniques.

A Ray1, J Powell2,  MJ Speakman3, NT Longford4, R DasGupta5, T Bryant6, S Modi6, J Dyer7, M Harris7, G Carolan-Rees1, N Hacking6

1Cedar, Cardiff University/Cardiff and Vale University Health Board, Cardiff, UK

2Centre for Health Technology Evaluation, National Institute for Health and Care Excellence, London, UK

3Department of Urology, Taunton and Somerset NHS Trust, Taunton, UK

4SNTL Statistics Research and Consulting, Department of Medicine, Imperial College London, London, UK

5Department of Urology, St. Mary’s Hospital, Imperial College Healthcare NHS Trust, London, UK

6Department of Interventional Radiology, Southampton General Hospital, University Hospital Southampton NHS Foundation Trust, Southampton, UK

7Department of Urology, Southampton General Hospital, University Hospital Southampton NHS Foundation Trust, Southampton, UK

 

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