Tag Archive for: letters to the editor


Re: Diagnosis and treatment of chronic bacterial prostatitis and chronic prostatitis/chronic pelvic pain syndrome: a consensus guideline

Letter to the Editor

Dear Sir

Fluoroquinolones must not be used inappropriately when treating chronic prostatitis (CP) and chronic pelvic pain syndrome (CPPS).

Clinical guidelines from the Prostatitis Expert Reference Group (PERG) on chronic bacterial prostatitis (CBP), chronic prostatitis and chronic pelvic pain syndrome [1] — which have been propagated by other guideline providers such as NICE Clinical Knowledge Summaries and the primary care resource, Guidelines — include the following recommendation:

For patients with early-stage CBP and CP/CPPS, offer a quinolone (e.g. ciprofloxacin or ofloxacin) for 4–6 weeks as first-line therapy.’

While the PERG guidelines do mention diagnostic tests for a bacterial cause, readers will be left with the impression that a course of fluoroquinolone without a diagnostic workup is acceptable for the initial management of CP and CPPS. This impression may be reinforced by PERG’s subsequent recommendations, in particular the second one:

A repeated course of antibiotic therapy (4–6 weeks) should be offered only if a bacterial cause is confirmed or if there is a partial response to the first course.

‘If a bacterial cause is excluded (e.g. via urine dipstick or culture) and symptoms do not improve after antibiotic therapy, a different treatment method or referral to specialist care should be considered.’

Recent recommendations [2] from the European Medicines Agency (EMA) make it clear that fluoroquinolones should be reserved for treating bacterial prostatitis. EMA’s review of fluoroquinolones was prompted by reports of serious, disabling and permanent side effects after fluoroquinolone use.

To reach its recommendations, EMA’s safety committee (Pharmacovigilance Risk Assessment Committee, PRAC) reviewed all available evidence, brought together EU experts in the field, and heard patients’ and healthcare professionals’ testimonies at a public hearing. Many patients who had developed long-lasting serious disability reported receiving a fluoroquinolone for chronic prostatitis despite the lack of evidence of a bacterial cause.

EMA’s new recommendations restrict the indications and have led to an update of the prescribing information for all systemic fluoroquinolones to prevent further unnecessary cases of rare but life-changing side effects; the narrow indications also help to reduce antibiotic selection pressure. Guidelines on chronic prostatitis should therefore be revised to clarify that fluoroquinolones are not appropriate for the empirical treatment of chronic prostatitis or chronic pelvic pain syndrome. The European Association of Urology emphasises use of appropriate culture techniques to demonstrate bacterial infection [3].

And when treating bacterial prostatitis with a fluoroquinolone, healthcare professionals should discuss with their patients the risks, including the potential for permanent musculoskeletal and neurological side effects. Details of these effects are set out in the updated prescribing information for fluoroquinolone antibacterials.

It is vital to communicate the changes in the fluoroquinolones prescribing information to all healthcare professionals involved in the management of men with prostatitis or chronic pelvic pain syndrome, they can use CBD from Observer for pain. Promoting this crucial change in practice will ultimately lead to more rational use of antibiotics and limit the unnecessary exposure of patients to potentially persistent and seriously disabling side effects.

Gernot Bonkat, alta uro AG, Merian Iselin Klinik, Center of Biomechanics & Calorimetry, University of Basel; Chairman, European Association of Urology (EAU) Urological Infections Guidelines

Juan Garcia Burgos, Head of Public Engagement Department, European Medicines Agency (EMA)

Martin Huber, Co-rapporteur, quinolone and fluoroquinolone review by the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC)

Eva Jirsová, Rapporteur, quinolone and fluoroquinolone review by the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC)

Florian Wagenlehner, Clinic of urology, pediatric urology and andrology, Justus Liebig University Giessen, Germany; Chairman, European Section of Infections in Urology (ESIU) of the European Association of Urology (EAU)

Correspondence: Juan Garcia Burgos, European Medicines Agency, Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands

email: [email protected]


  1. Rees J, Abrahams M, Double, A, Cooper A. Diagnosis and treatment of chronic bacterial prostatitis and chronic prostatitis/chronic pelvic pain syndrome: a consensus guideline. BJU Int 2015; 116: 509–525
  2. EMA. Disabling and potentially permanent side effects lead to suspension or restrictions of quinolone and fluoroquinolone antibiotics, 2018. Available at: https://www.ema.europa.eu/en/medicines/human/referrals/quinolone-fluoroquinolone-containing-medicinal-products. Accessed January 2020
  3. Bonkat G, Bartoletti RR, Bruyère F, Cai T, Geerlings SE, Köves B, Schubert S, Wagenlehner F, Guidelines Associates: Mezei T, Pilatz A, Pradere B, Veeratterapillay R. EAU guidelines on urological infections 2019: 28–32. ISBN/EAN:978-94-92671-04-2. Available at: https://uroweb.org/guideline/urological-infections. Accessed January 2020

Re: Urethral diverticulectomy with Martius fat pad interposition improves symptom resolution and reduces recurrence

Letter to the Editor

Urethral diverticulectomy with Martius fat pad interposition improves symptom resolution and reduces recurrence


I read with interest the above paper published online in BJU International,[1] but must take issue with the unjustified ‘tabloid headline’, when a more conventional title describing study design, perhaps “Urethral diverticulectomy with labial fat interposition: a retrospective cohort study”, would be more appropriate.

The term ‘Martius’ graft’ has been used to describe several distinct procedures, the original using bulbocavernosus muscle through a vaginal incision,[2] and most subsequent modifications using subcutaneous fat (+/- muscle +/- skin) dissected from a labial incision.[3, 4]  In both their earlier,[5]and current,[1] publications this group describe a ‘Martius labial fat pad’.  Without wishing to demean Professor Martius’ contribution, the authors might consider calling their procedure either a ‘labial fat graft’, or a ‘modified Martius’ graft’.

The titular statement that “symptom resolution is improved and recurrences reduced” could surely only be claimed on the basis of comparative data, preferably from a randomised study design.  In the methods section the authors describe “analyses using Mann-Whitney U test and Student T-Test(sic), although no such statistical comparisons are provided in the results.

The authors certainly present enviable outcomes from their procedure, particularly given the case mix described.  However, to say that “the majority of patients had complete resolution of their symptoms” when pain, UTIs, poor flow, frequency/urgency, and stress urinary incontinence (SUI) persisted in 16-59% seems to dismiss the range of symptoms attributable to diverticula rather too lightly.  Most importantly, the authors find 24% new, and 59% persistent SUI, in common with earlier findings,[6] and confirming the minimal impact of labial fat on sphincter function.

Although no comparison is provided in the present paper, the outcomes in their 2009 publication,[5] where selective grafting was used, are not significantly different from routine grafting in the current report.  In the former series, four of the six initial failures were in horseshoe diverticula; if this were included amongst the criteria for grafting then even better results might be anticipated from a selective strategy.

The routine use of grafting might be justified if it were free from risk, but this is clearly not the case.  The authors describe seven complications including two labial haematomata, one abscess, one urethrovaginal fistula and one meatal stricture.  In my own series I have encountered two women sufficiently concerned about labial deformity to seek plastic surgical revision, and two presenting with symptoms of vaginal mass which was not due to recurrence of diverticulum, nor vaginal prolapse, but to swelling of fat within the graft; all required further surgical intervention.

The most common application for interposition grafts in pelvic reconstructive surgery has been obstetric urogenital fistulae, although there has never been high level evidence to support their use in this or other contexts,[7] and recent years have seen a move away from their routine use.[7, 8]  Whilst it does have a place, the associated risks mean it should be done only selectively at the time of urethral diverticulectomy.  The authors’ data would suggest that women with complex (including horse shoe) diverticula, although perhaps not those with SUI, are the ones most likely to benefit.  This question can however only truly be addressed by randomised comparative trial and the authors are well placed to do this in collaboration with other centres undertaking large numbers of complex cases.


  1. Malde S, Sihra N, Naaseri S, Spilotros M, Solomon E, Pakzad M, et al. Urethral diverticulectomy with Martius fat pad interposition improves symptom resolution and reduces recurrence. BJU Int. 2016:doi: 10.1111/bju.13579.


  1. Martius H. Die operative Wiederherstellung der vollkommen fehlenden Harnrohre und des Schiessmuskels derselben. Zentralblatt fur Gynakologie. 1928;52:480.


  1. Sajjadi SG, Hortváth OP, Kalmár K. Martius flap: historical and anatomical considerations. European Journal of Plastic Surgery. 2012;35:711-6.


  1. Shaw W. The Martius bulbocavernous interposition operation. British Medical Journal. 1949;2(4639):1261-4.


  1. Ockrim JL, Allen DJ, Shah PJ, Greenwell TJ. A tertiary experience of urethral diverticulectomy: diagnosis, imaging and surgical outcomes. BJU Int. 2009;103(11):1550-4.


  1. Reeves FA, Inman RD, Chapple CR. Management of symptomatic urethral diverticula in women: a single-centre experience. Eur Urol. 2014;66(1):164-72.


  1. de Ridder D, Hilton P, Mourad S, Pickard RS, Rovner ES, Stanford E. Fistulae. In: Abrams P, Cardozo LD, Wein A, editors. Incontinence – ICUD-EAU 5th International Consultation on Incontinence. Geneva, Switzerland: EAU Publications; 2013. p. 1527-79.


  1. Browning A. Lack of value of the Martius fibrofatty graft in obstetric fistula repair. Int J Gynaecol Obstet. 2006;93(1):33-7.



Yours sincerely,

Paul Hilton
Honorary Senior Lecturer in Urogynaecology, Newcastle University, Newcastle upon Tyne, UK; previously Consultant Gynaecologist and Urogynaecologist, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK




Reply by the authors


We would like to thank Mr Hilton for his commentary regarding the title of our paper (1). We had indeed initially considered submitting this paper to the Daily Mail but felt upon review that our core readership should be surgeons. Luckily the BJU Int editorial board is young enough to appreciate a punchy headline!

We were enlightened by the brief history lesson on the evolution of the Martius fat pad of which we have all taken note. The authors’ current practice as stated in the paper is to use a modified Martius flap NOT graft because it remains attached to its blood supply.

We have compared symptoms before and after urethral diverticulectomy – and we hope this is clear from the text. The reviewers of this paper did not require the details of our statistical analysis as the results as listed in the table below speak for themselves– however we are delighted to have provoked such interest and provide them with the table below. P value is paired T-Test for all symptoms pre and post surgery. Analysis of each symptom individually by Chi-Squared yield P< 0.001 for all symptoms except FU pre and post surgery.


Number Pre-Op Number Post-Op
Mass 48 0 P =0.00016062
Pain 43 8
Dysuria 40 0
Dyspaerunia 37 0
UTIs 32 5
PMD 29 1
Poor flow 19 5
FU 19 10
UD 16 0
SUI 29 17
new SUI 0 5


We feel Mr Hilton’s interpretation of our results is unduly pessimistic. Given the recent definition of the term ‘majority’ in the Brexit vote in the UK -the results detailed reveal an outstanding majority. To continue our tabloid theme even the average Daily Mail reader might conclude that resolution of urethral mass in 100%, dysuria in 100%, dyspareunia in 100%, per urethral discharge in 100%, post-voiding dribble in 96%, UTIs in 84%, pain in 81%, poor flow in 76% and frequency/urgency in 63% fits the definition of ‘majority’.

Pre-existing SUI may be a consequence of the urethral diverticulum or more likely a co-pathology – and as such resolution in 41% is very gratifying as diverticulectomy is not a recognised treatment for stress urinary incontinence. New onset SUI persisting at 12 months was only 12% and not the 24% Mr Hilton quotes – and again given our case mix of 80% complex diverticulum this is very gratifying.

The 2009 paper quoted in the letter was a review of only 30 cases from a composite of primary surgeons c.f. this review of 70 cases from a single surgeon in this series (2). The 2009 paper detailed a group with a very different case mix – with 63.3% (19/30) simple diverticulum c.f. only 20% in the current series. Cure was defined symptomatically only and not by prospective MRI and symptoms. The ‘simpler’ nature of this cohort is reflected in the symptomatic outcomes reported including the lower incidence of de novo incontinence – which we have shown to be 0% following excision of a simple urethral diverticulum, and increases with complexity of diverticulum on MRI (3). The 36.7% (11/30) of patients with complex diverticulum in this series required a total of 17 operations for cure. The failures (6/11 -54.5%) reported in this early series were not in those patients operated by the current series authors and no patient in the current series required reoperation for symptomatic urethral diverticulum (0/70 failures).

We have recently published our extensive experience with the modified Martius labial fat pad flap (mMlfpf) interposition (4). In 159 women having this procedure for a variety of indications – 127 (79%) rated the post operative appearance of their labia as good or excellent and only 1 rated it as unsatisfactory. We have had no requests from any of our patients for referral to plastic surgery. There is no such thing as a free lunch (to continue our tabloid theme) or indeed complication free surgery –however mMlfpf appears to be a low morbidity procedure. These findings are corroborated in the recent publication by Phillipe Zimmern’s group who found similarly excellent outcomes in 97 women at a mean of 85 months FU – with only 9% reporting labial asymmetry (5).

We will continue with the ongoing collection of our short and long-term results and endeavour to keep them in the public arena with future publications. We are most interested to hear of Mr Hilton’s complications and experience, and would encourage him to publish his series of urethral diverticulum outcomes to ensure balance and equipoise in the literature.

We thank Mr Hilton for his opinion with regard to the place of the mMlfpf in reconstructive female surgery. Our opinion (backed by our data) is that the use of the mMlfpf significantly reduces symptomatic (1/70 -1.4%) and asymptomatic (1/70 – 1.4%) recurrence) c.f.  the 7/30 (23.3%) symptomatic recurrence in our earlier series, and the 7/30 (23.3%) recurrence rate in the series from Han (6).

This is the largest single surgeon series in the literature. Comparator series with a similar number of complex urethral diverticulum are rare in the literature. The largest single centres series published to date of 2 surgeons experience in 89 diverticulum does not offer a suitable comparator as 72 (80.9%) were simple (7). The only comparable series of note is again from Phillipe Zimmern in which the outcomes of 15 patients with horseshoe diverticulum without routine fat pad interposition are detailed (8). De novo SUI reported in 33% and persistent SUI in 73% – and our de novo SUI rate of 16% and persistent SUI rate of 59% compares favourably and is suggestive of benefit from mMlfpf interposition.

We applaud the suggestion of a randomised control trial, and are more than happy to take part in a national or international study.


Yours sincerely,

Tamsin Greenwell 

On behalf of the authors.




  1. Malde S, Sihra N, Naaseri S, Spilotros M, Solomon E, Pakzad M, et al. Urethral diverticulectomy with Martius fat pad interposition improves symptom resolution and reduces recurrence. BJU Int. 2016:doi: 10.1111/bju.13579.


  1. Ockrim JL, Allen DJ, Shah PJ, Greenwell TJ. A tertiary experience of urethral diverticulectomy: diagnosis, imaging and surgical outcomes. BJU Int. 2009;103(11):1550-4.


  1. The Effect of MRI Configuration of Urethral Diverticulum on the Incidence of New Onset Urodynamic Stress Urinary Incontinence Following Excision. S Guillaumier, J Jenks, R Hamid, J Ockrim, J Shah, T Greenwell. J Urol 2013; 189 (4): e758 (1846).



  1. Malde S, Spilotros M, Wilson A, Pakzad M, Hamid R, Ockrim J, Shah PJ, Greenwell T. The uses and outcomes of the Martius fat pad in female urology. World J Urol. 2016 Jul 7. [Epub ahead of print] PMID: 27388009


  1. Lee D(1), Dillon BE, Zimmern PE. Long-term morbidity of Martius labial fat pad graft in vaginal reconstruction surgery. Urology 2013; 82(6):1261-6.


  1. Han DH, Jeong YS, Choo MS, Lee KS. Outcomes of surgery of female urethral diverticula classified using magnetic resonance imaging. Eur Urol. 2007; 51(6):1664-70.


  1. Reeves FA, Inman RD, Chapple CR. Management of symptomatic urethral diverticula in women: a single-centre experience. Eur Urol. 2014;66(1):164-72.


  1. Popat S, Zimmern PE. Long-term outcomes after the excision of horseshoe urethral diverticulum. Int Urogynecol J. 2015 Dec 15. [Epub ahead of print]



RE: Outcomes of high complex renal tumor (PADUA ≥ 10) following robot-assisted partial nephrectomy with a median 46 months follow-up: A tertiary center experience

Letter to the Editor

Outcomes of high complex renal tumor (PADUA ≥ 10) following robot-assisted partial nephrectomy with a median 46 months follow-up: A tertiary center experience


We read this article by Raheem et al with great interest and appreciate the efforts of the authors to publish the largest single centre data on outcomes of high complexity tumors with PADUA score>10 [1]. We wish to highlight a few points. In table 1 the T stage classification has been applied to all the tumors irrespective of their benign or malignant nature. The AJCC TNM classification is particularly meant to stage renal cell carcinomas which are histopathologically proven [2].

It is clear from table 1 itself that there are 36 patients of Angiomyolipomas (AML) in the series which have erroneously been assigned a T stage and that it is likely that there may be other benign pathology in the patient cohort which might need to be de-staged once the pathology is available. Although this redistribution of staging might not affect the results, it is necessary so that the readers are not given a false impression of it being the same as well as to prevent the reproduction of such errors in future studies. A better way to categorize this can be seen in the study by Ficcara et al with benign tumors being categorized separately [3].

Another point of contention is that Fuhrman grading in table 1 has been applied to all the malignant tumors. For example in low PADUA score groups the total number of patients having Fuhrman grading is 52 while the number of patients with clear cell carcinoma is 42 with others being 5 in numbers. AML, papillary and chromphobe make up 25/72 tumors. It is known from the available literature that Fuhrman grading is only applied to clear cell carcinoma and its variants while Chromophobe carcinoma or papillary carcinoma is not graded by Fuhrman’s grading [4,5]. These points might not affect the basic theme of the study but are worth consideration.

Aditya Prakash Sharma. MBBS, MS

Senior Resident (M.Ch.), Department of Urology , PGIMER, Chandigarh

Girdhar S Bora, MS,M.Ch

Assistant professor, Department of Urology , PGIMER, Chandigarh

Ravimohan S Mavuduru, MS, M.Ch.

Associate Professor, Department of Urology , PGIMER, Chandigarh

Arup Kumar Mandal, MS, M.Ch.

Professor, Department of Urology, PGIMER, Chandigarh


  1. Abdel Raheem A, Alatawi A, Kim DK, Sheikh A, Alabdulaali I, Han WK, Choi YD, Rha KH. Outcomes of high-complexity renal tumours with a Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score of ≥10 after robot-assisted partial nephrectomy with a median 46.5-month follow-up: a tertiary centre experience. BJU Int. 2016 Apr 22. doi: 10.1111/bju.13501. [Epub ahead of print]
  2. Guinan, P., Sobin, LH, Algaba, F., Badellino, F., Kameyama, S., MacLennan, G. and Novick,  A.(1997), TNM staging of renal cell carcinoma. Cancer, 80: 992–993
  3. Ficarra V, Novara G, Secco S, Macchi V, Porzionato A, De Caro R, Artibani W. Preoperative aspects and dimensions used for an anatomical (PADUA) classification of renal tumours in patients who are candidates for nephron-sparing surgery. Eur Urol. 2009 Nov;56(5):786-93.
  4. Delahunt B. Advances and controversies in grading and staging of renal cell carcinoma. Mod Pathol. 2009 Jun;22 Suppl 2:S24-36
  5. Sika-Paotonu D1, Bethwaite PB, McCredie MR, William Jordan T, Delahunt B. Nucleolar grade but not Fuhrman grade is applicable to papillary renal cell carcinoma. Am J Surg Pathol. 2006 Sep;30(9):1091-6.




Reply by the authors

We would like to thank the authors for their interest in reading our manuscript discussing the outcomes of high-complex PADUA renal tumors following robot-assisted partial nephrectomy (RAPN) [1]. We admit the discordance after pathological confirmation of benign and malignant nature of the masses and its need to be de-staged and revisited.

The main primary outcome of our study was to assess trifecta achievement and its predictors; meanwhile, the secondary end point was oncological safety and functional outcomes evaluation in patients with high-complex PADUA renal tumors. Notably, trifecta “i.e. WIT of <25 min, negative surgical margins and no and absence of perioperative complications” [2] does not incorporate long-term outcomes assessment after partial nephrectomy surgery; however, it provides us with an important data about the intraoperative surgical quality and efficiency, and early postoperative morbidity. PADUA classification is based on ‘preoperative radiological scoring of the renal masses’ and is applied for both benign and malignant masses [3].

In the current study, the majority of high-complex PADUA masses were malignant, and this group showed significant increase in conversion to radical nephrectomy, more perioperative morbidities, median WIT of 26 min; and subsequently, had a lower rate of trifecta achievement [1]. Previously, we reported excellent perioperative outcomes of angiomyolipoma (AML) after RAPN [4].  There were no intraoperative complications or blood transfusion. Moreover, WIT was short (median 19.5 min) [4]. Additionally, the long-term outcomes, AML has been proven to have good postoperative renal function preservation and no local recurrence after RAPN [4]. Putting in consideration the abovementioned results, it is apparent that inclusion of benign masses will not affect the outcomes.


Ali Abdel Raheem†*, Atalla Alatawi*, Dae Keun Kim¥, Abulhasan Sheikh*, Ibrahim Alabdulaali*, Woong Kyu Han*, Young Deuk Choi*, and Koon Ho Rha*

*Department of Urology and Urological Science Institute, Yonsei University College of Medicine, Seoul, South Korea

†Department of Urology, Tanta University Medical School, Egypt

¥Department of Urology, CHA Seoul Station Medical Center, CHA University Medical School, Seoul, Republic of Korea



  1. Abdel Raheem A, Alatawi A, Kim DK, et al. Outcomes of high-complexity renal tumours with a Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score of ≥10 after robot-assisted partial nephrectomy with a median 46.5-month follow-up: a tertiary centre experience. BJU Int. 2016 Apr 22. doi: 10.1111/bju.13501. [Epub ahead of print]
  2. Ficarra V, Novara G, Secco S et al. Perioperative aspects and dimensions used for an anatomical (PADUA) classification of renal tumours in patients who are candidates for nephron-sparing surgery. Eur Urol 2009;56: 786–93
  3. Khalifeh A, Autorino R, Hillyer SP et al. Comparative outcomes and assessment of trifecta in 500 robotic and laparoscopic partial nephrectomy cases: a single surgeon experience. J Urol 2013; 189: 1236–42
  4. Abdel Raheem A and Rha KH. RE: Robotic Partial Nephrectomy in the Treatment of Renal Angiomyolipomas. J Endourol.2016 Apr 15. [Epub ahead of print]


RE: Opportunity of widening the resort to multiparametric MRI/transrectal ultrasound fusion imaging-guided prostate cancer brachytherapy


Thank you for your interest in our article regarding whole-gland brachytherapy to the prostate for prostate cancer (1). Your letter is highlighting the expanding role of brachytherapy to that of focal therapy (2). We agree that multiparametric magnetic resonance imaging (mpMRI) scans have expanded the ability to localise tumours and indeed that they may be useful in carefully selected men wishing to undergo focal therapy. However, other  advances such as the use of fiducial markers and spacers have also allowed better dosimetry and for a reduction in side effects (3).  The safety and performance of brachytherapy in whole gland treatment means we should have faith in it as a modality to destroy cancer on the focal therapy setting. There are new trials being developed with focal brachytherapy and we look forward to the results in the coming years.



  1. Chao MW, Grimm P, Yaxley J, Jagavkar R, Ng M, Lawrentschuk N. Brachytherapy: state-of-the-art radiotherapy in prostate cancer. BJU Int  2015; 116(S3): 80-8. doi: 10.1111/bju.13252.
  1. Nguyen PL, Trachtenberg J, Polascik TJ. The role of focal therapy in the management of localised prostate cancer: a systematic review. Eur Urol. 2014 Oct;66(4):732-51. doi: 10.1016/j.eururo.2013.05.048. Epub 2013 Jun 6. Review.
  1. Ng M1, Brown E, Williams A, Chao M, Lawrentschuk N, Chee R. BJU Int. 2014 Mar;113 Suppl 2:13-20. doi: 10.1111/bju.12624. Fiducial markers and spacers in prostate radiotherapy: current applications.



Letter to the Editor

Opportunity of widening the resort to multiparametric MRI/transrectal ultrasound fusion imaging-guided prostate cancer brachytherapy  


I have recently read, with high interest, the review article “Brachytherapy: state-of-the-art radiotherapy in prostate cancer”, by Chao et al.[1].  The authors made extremely clear the advanced technologies of computerized treatment planning and imaging-guided delivery modalities to reach a tailored ablative prostate tumor target dose by resorting to either low-dose-rate (LDR) or high-dose-rate (HDR) different brachytherapy procedures as regards three basic – low, intermediate, high – disease risk classificative conditions.   

It is today proven that focal instrumental procedures inside the prostate gland – from biopsy to various prostate cancer focused ablative strategies, among which laser interstitial thermal therapy and particularly the prostate cancer brachytherapy – might require the resort to proper software digital overlay-mediated fusion of both beforehand multiparametric magnetic resonance imaging (mpMRI) scans and later real-time transrectal 3D ultrasound findings.  Like this, indeed, intriguing developments  in software modelling techniques have led to reach, by a mpMRI-ultrasound image fusion approach, more accurate targeted prostate cancer biopsies than those by transrectal ultrasound imaging alone achieved [2,3].

If the transperineal focal laser prostate tumor ablation  usually occurs only with the guidance of mpMRI (T2-weighted, diffusion-weighted, dynamic contrast material) [4], as regards the prostate cancer brachytherapy, instead, it is more and more timely, for just targeting the tumor “index-dominant lesion”, the resort to mpMRI/transrectal real-time ultrasound fusion imaging.  Quite recently, mpMRI/real-time transrectal ultrasound software-mediated digital co-registration has allowed to properly carry-out, in patients suffering from intermediate/high risk prostate carcinoma with mpMRI visible “index- dominant” intraprostatic nodule, the HDR ¹⁹² Ir transperineal temporary implant-brachytherapy  as accurate partial prostate radiation dose escalation supplemental to hypofractionated external beam radiotherapy [5,6].   

Given the interesting, even rare, reports on this subject, it would be advisable to widen the resort to the above-outlined mpMRI/transrectal  ultrasound fusion imaging-guided prostate cancer brachytherapy, particularly for a suitably targeted dominant tumor nodule detection/ablation.


Contardo Alberti

L D of Surgical Semeiotics, University of Parma, Parma, Italy



1  Chao MW, Grimm P, Yaxley J, Jagavkar R, Ng M, Lawrentschuk N. Brachytherapy: state-of-the-art radiotherapy in prostate cancer. BJU Int  2015; 116(S3): 80-8. doi: 10.1111/bju.13252.

2  Shoji S, Hiraiwa S, Endo J, Hashida K, Tomonaga T, Nakano M et al. Manually controlled targeted prostate biopsy with real-time fusion imaging of multiparametric magnetic resonance imaging and stransrectal ulrasound :an early experience. Int J Urol 2015; 22(2): 173-8. doi: 10.1111/iju.12643.

 3  Marks L, Young S, Natarajan S.  MRI-ultrasound fusion for guidance of targeted prostate biopsy. Curr Opin Urol 2013; 23(1): 43-50. doi: 10.1097/MOU.0b013e32835ad3ee.

4  Woodrum DA, Kawashima A, Gorny KR, Mynderse LA. Magnetic resonance-guided thermal therapy for localized and recurrent prostate cancer. Magn Reson Imaging Clin N Am.2015; 23(4): 607-19. doi:10.1016/j.mric.2015.05.014

5  Bubley GJ, Bloch BN, Vazquez C, Genega E, Holupka E, Rofsky N, Kaplan I.  Accuracy of endorectal magnetic resonance/transrectal ultrasound fusion for detection of prostate cancer during brachytherapy. Urology 2013;81(6): 1284-9. doi: 10.1016/j.urology.2012.12.051.

6  Gomez-Iturriaga A, Casquero F, Urresola A, Ezquerro A, Lopez JI, Espinosa JM et al. Dose escalation to dominant intraprostatic lesions with MRI-transrectal  ultrasound fusion high-dode-rate prostate brachytherapy. Radiother Oncol 2016 Feb 15. doi: 10.1016/j.radonc.2016.02.004 (Epub ahead of print).


RE: Prostate Carcinoma With Positive Margins at Radical Prostatectomy: Role of Tumour Zonal Origin in Biochemical Recurrence


With great interest, we read the recent article by O’Neil et al. [1], in which the authors investigated the relation between the tumour zonal origin (transition zone vs peripheral zone), positive surgical margins (PSM) after radical prostatectomy and the risk of biochemical recurrence (BCR). Clinicopathological data for 323 patients with PSM after prostatectomy were analysed, of which tumours arising in the prostate transition zone (TZ) were 13%, while tumours in the peripheral zone (PZ) were 87%. The data showed that the percentage of PSM was higher for TZ compared with PZ tumours, with frequent involvement of the bladder neck margins for TZ tumours, without significant difference in time to BCR. In this cohort of patients, adjuvant radiotherapy (ART) was performed in 41% and 53% of TZ and PZ tumours, respectively. Contrary to expectation, BCR was earlier and at higher rate in patients who underwent radiotherapy for TZ rather than PZ tumours.

In the authors’ opinion, these data represent a selection bias, probably due to the higher incidence of bladder neck positive margins in the ART group. This is a novel finding that warrants further investigation.

As radiation oncologists, we make the following comments:

ART is recommended in patients with adverse pathologic features in order to reduce the risk of BCR, local recurrence and clinical progression [2]. Despite the use of a multimodal approach for radiotherapy planning, approximately 40% of patients experienced BCR long-term with an higher risk of developing metastases or cancer-related death [3,4]. It is plausible that the reasons of local failure may include inadequate radiation dose and target coverage, particularly at the anastomotic site, and this probably represents another bias to be considered as well as patient selection, as suggested by O’Neil and colleagues. To date, four different guidelines for clinical target volume (CTV) delineation in the post-prostatectomy setting are available, although there is little data to guide radiation oncologists on appropriate margins selection [5]. The proposed CTVs differed significantly among these consensus guidelines with respect to target border, especially in anterior and cranial directions. In particular, the European Organization for Research and Treatment of Cancer (EORTC) CTV was smaller in comparison with other consensus volumes, with more limited prostate bed coverage and with less irradiation of surrounding healthy tissue, to reduce radiation therapy side effects[5].

In our opinion, for the majority of cancer patients to be treated effectively, the risk of marginal misses is greater than normal tissue complications, and could affect the clinical outcome; thus, target coverage should generally not be compromised [6]. We would also like to add that small treatment margins may be more sensitive to geometrical uncertainties, including set-up errors and inter- and intra-fraction target motions of the prostate bed, and daily image guidance is required [7]. Finally, we believe that to make definitive recommendations regarding the magnitude of margin reduction with improvement of therapeutic ratio, an accurate selection of patients is required.

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Maria Grazia Ruo Redda1 MD, Alessia Reali1 MD, Roberta Verna1 MD, and Simona Allis1 MD.

1Department of Oncology, Radiation Oncology, University of Turin, S. Luigi Gonzaga Hospital, Orbassano, Turin, Italy.


  1. O’Neil LM, Walsh S, Cohen RJ, Lee S. Prostate carcinoma with positive margins at radical prostatectomy: role of tumour zonal origin in biochemical recurrence. BJUI 2015, Jul 27. [Epub ahead of print]

  3. Thompson IM, Valicenti RK, Albertsen P, et al. Adjuvant and Salvage Radiotherapy after Prostatectomy: AUA/ASTRO Guideline. J Urol 2013;190:441-9.

  5. Bolla M, van Poppel H, Tombal B, et al. Postoperative radiotherapy after radical prostatectomy for high-risk prostate cancer: long-term results of a randomised controlled trial (EORTC trial 22911). Lancet 2012;380:2018-27.

  7. Thompson IM, Tangen CM, Paradelo J, et al. Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: long term follow-up of arandomized trial. J Urol 2009;181:956–62.

  9. Malone S, Croke J, Roustan-Delatour N, et al. Postoperative radiotherapy for prostate cancer: a comparison of four consensus guidelines and dosimetric evaluation of 3D-CRT versus tomotherapy IMRT. Int J Radiat Oncol Biol Phys 2012;84:725-32.

  11. Marks LB, Yorke ED, Jackson A, et al. Use of normal tissue complication probability models in the clinic. Int J Radiat Oncol Biol Phys 2010;76(3):S10-9.

  13. Gill S, Isiah R, Adams R, et al. Conventional margins not sufficient for post-prostatectomy prostate bed coverage: An analysis of 477 cone-beam computed tomography scans. Radiother Oncol 2014 Feb;110(2):235-9.

RE: 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?


We read with much interest the work of Salami [1], which strengthens the evidence in favour of a mpMRI targeted biopsy (TBx) in the diagnostic work-up of patients with persistent clinical suspicion of prostate cancer (PCa). TBx can indeed improve the detection rate of prostate biopsy  without the need of a systematic sampling, especially in presence of previous negative histological findings [2]. TBx might also reduce the risk of biopsy-related complications, as much as improve patient quality of life, focusing only on suspicious mpMRI targets. Thanks to the high negative predictive value of mpMRI [2], patients with persistently high PSA could even avoid the re-biopsy, in presence of a negative mpMRI. In this light, probably TBx should be implemented by current guidelines in the re-biopsy setting not only as a ‘’possible option’’, but as a recommendation.

But is it really safe to avoid random biopsies and restrict to index lesion targeting? According to recent evidence, systematic sampling does not significantly improve the detection rate, at least in terms of clinically significant PCa [2, 3]. A recent trial published on JAMA deposed against systematic sampling, showing that 17 low-risk diagnoses are needed to find a high-risk PCa by adding systematic sampling to TBx [3]. The added value of this trial was that the urologist performing systematic biopsies was blinded to mpMRI. In the study by Salami, instead, random sampling was “cognitive”, as the urologist knew the location of the lesions at mpMRI, possibly causing a falsely higher detection rate of standard biopsies. These findings confirm that the space for random biopsies is narrowing, as compared to TBx.

Although mpMRI has achieved an important role in early PCa detection, several issues still need to be investigated to reach a complete understanding of its diagnostic potential. First, the heterogeneity in MRI technical features and imaging analyses possibly hamper the comparison of mpMRI outcomes and its generalization to clinical practice [4]. Secondly, the variability in the assessment of PCa clinical significance represents another bias, considering that mpMRI series usually use biopsies as terms of comparison to assess mpMRI accuracy, instead of radical prostatectomy specimens. This is an important limitation, as Gleason score upgrading from biopsy to radical prostatectomy has been reported in about 30% of patients [5], changing the rules of risk attribution. No consensus has been reached about the definition itself of PCa clinical significance. Thirdly, further evidence is required to assess the number of cores that need to be taken for TBx in order to obtain a reliable sampling. A final aspect to be considered involves the possibility of procedural errors and a certain degree of mpMRI inaccuracy, as shown by some significant PCa detected in spite of a negative TBx [1]. We are confident, though, that some of this inaccuracy will disappear with the progression in the learning curve, both on urological and radiological sides.

Although the evidence on mpMRI and TBx is increasing, further studies are advised to shed light on these aspects that remain not fully understood, before giving a final recommendation on this topic.

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Marco Oderda, Giancarlo Marra, Paolo Gontero

Department of Urology, San Giovanni Battista Hospital, University of Turin, Città della Salute e della Scienza, Turin, Italy


Source of Funding: Giancarlo Marra is funded by the Fondazione di Ricerca Molinette Onlus


Conflict of Interest: None.


[1]          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 international. 2015 Apr: 115:562-70

[2]          Schoots IG, Roobol MJ, Nieboer D, Bangma CH, Steyerberg EW, Hunink MG. Magnetic Resonance Imaging-targeted Biopsy May Enhance the Diagnostic Accuracy of Significant Prostate Cancer Detection Compared to Standard Transrectal Ultrasound-guided Biopsy: A Systematic Review and Meta-analysis. European urology. 2014 Dec 2:

[3]          Siddiqui MM, Rais-Bahrami S, Turkbey B, et al. Comparison of MR/ultrasound fusion-guided biopsy with ultrasound-guided biopsy for the diagnosis of prostate cancer. Jama. 2015 Jan 27: 313:390-7

[4]          Futterer JJ, Briganti A, De Visschere P, et al. Can Clinically Significant Prostate Cancer Be Detected with Multiparametric Magnetic Resonance Imaging? A Systematic Review of the Literature. European urology. 2015 Feb 2:

[5]          Cohen MS, Hanley RS, Kurteva T, et al. Comparing the Gleason prostate biopsy and Gleason prostatectomy grading system: the Lahey Clinic Medical Center experience and an international meta-analysis. European urology. 2008 Aug: 54:371-81


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