Optimising prostate biopsy
BMJ 2012; 344 doi: https://doi.org/10.1136/bmj.d8201 (Published 09 January 2012) Cite this as: BMJ 2012;344:d8201
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Evaluating and analyzing complications of prostate needle biopsies are certainly crucial when discussing benefits and harms of biopsies in times of increasing number of biopsies and biopsy cores. The suggestions made by Stainsby may sound attractive at first sight but do not reflect our current understanding , nore are they supported by the current literature.
Firstly, the studies quoted were exclusively performed in pre- or early PSA eras where cancer features were different and patient cohorts not comparable to today's average patient presenting with early prostate cancer. Pathological analysis has evolved as well and Bastacky and Epstein (1), who authored the study in 1991, certainly do not criticize or refute the validity and necessity of prostate biopsies today.
In their study , most of the patients underwent Tru Cut Needle Biopsy (16 Gauge) versus a much thiner 18 gauge needle today and case numbers were far from significant to identify differences or show similarities.
The common understanding in the early '90s was that eventually perineal biopsies may be associated with increased tumor tracking and eventually seeding. However, Ryan et al reviewing the literature, could only report a “third case” of tumor seeding in patient undergoing transperineal biopsies of the prostate (2).
We reviewed the morbidity of prostate biopsies in the early prostate cancer detection study (EPCDS) and found no evidence for tumor seeding in those patients (3). Although this was not specifically an endpoint of the study, no clinical nor pathological correlation was identified. Similarly, Loeb et al, who analysed a total of 10 474 prostate needle biopsies, performed between in 1993 and 2011 in the European Randomized Study of Screening for Prostate Cancer (Rotterdam section), did not report any evidence for tumor seeding or tracking (4).
In summary, reflections and suggestions as mentioned by Stainsby are always attractive for those screening adversaries trying to identify harms and drawbacks associated with either PSA as a marker or the biopsy procedure by itself. Whereas most of the critics focus on PSA, little has been reported regarding the biopsy procedure. Although this represents a new target and topic, the current discussion on tumor seeding and tracking lacks scientific evidence and certainly reflects even less our current understanding of the harms associated with prostate biopsies.
Literature
1. Bastack SS, Walsh PC, Epstein JI. Needle Biopsy aasociated tumor tracking of adenocarcinoma of the prostate. J Urol 1991; 145 (5): 1003-1007
2. Ryan PG, Peeling WB. Perineal prostatic tumour seedling after 'Tru-Cut' needle biopsy: case report and review of the literature. Eur Urol. 1990;17(2):189-92.
3. Djavan B, Waldert M, Zlotta A, Dobronski P, Seitz C, Remzi M, Borkowski A, Schulman C, Marberger M.
Safety and morbidity of first and repeat transrectal ultrasound guided prostate needle biopsies: results of a prospective European prostate cancer detection study.
J Urol. 2001 Sep;166(3):856-60
4. Loeb S, van den Heuvel S, Zhu X, Bangma CH, Schröder FH, Roobol MJ.
Infectious Complications and Hospital Admissions After Prostate Biopsy in a European Randomized Trial.
Eur Urol. 2012 Jan 5. [Epub ahead of print]
Competing interests: No competing interests
Short term outcomes of prostate biopsy
It is disappointing to note that in the research report from Rosario et al,1 and the editorial by Djavan and Rocco,2 no mention is made of the potential of the transrectal ultrasound guided prostate biopsy to cause needle track seeding or extra-capsular extension of tumour.
This possibility was identified as long ago as 19913 and acknowledged in 1997 in a report commissioned by the NHS Research and Development Health Technology Assessment Programme 4. The authors noted that diagnostic tests used to determine which tumours were localised within the prostate were unreliable, with approximately one half of all tumours upstaged following surgery. Among the Report’s recommendations for future research were,
• Definition of the optimum method of diagnosis
• Investigation of the consequences of increasing numbers of biopsies particularly tumour seeding and infectious complications
• Improving staging performance………
This research is yet to take place, and these recommendations were not addressed either by the ProtecT trial5 or by the ProBE study reported by Rosario et al.
Djavan and Rocco concede that, ‘complications related to trans-rectal ultrasound guided prostate biopsy are an integral part of the current discussion about PSA screening and early detection, as well as the need for repeat and saturation biopsies’, but they acknowledge that the biopsy procedure is not yet standardised in relation to ‘the number of cores taken, the direction of the biopsy needle, the area targeted, and three dimensional placement of the needles’. However, in describing the limitations and risks of this procedure they fail to consider its inevitable potential to cause local tumour spread.
In 2008, Djavan and Marihart6 referred to a previous publication by Djavian et al7 comparing the results of initial and repeat biopsies. They reported results showing that, of the ‘cancers detected on initial (n = 231) and repeat biopsy (n = 83), 148/231 (64%) and 56/83 (67.5%), respectively, were clinically localised disease.’ From the initial biopsy group 138/148 (93.2%) and 53/56 (94.6%) of the repeat biopsy group underwent radical prostatectomy. At subsequent histopathologic examination 58% and 60.9% had organ-confined disease, and positive surgical margins were noted in 23% and 18% respectively.’ Thus, in these two groups 42% and 39.1% respectively were upstaged at histology, with the finding of extra-capsular tumour extension. Similar inaccuracy of staging and inadequate tumour removal continues to be reported8-17. The possibility that these disappointing results may be due to tumour seeding and local spread outside the capsule at the time of biopsy has still not been investigated.
I suggest that the longer-term outcomes of prostate cancer treatment will continue to be poor until the risk of multi-needle biopsy techniques causing capsular damage overlying tumour tissue is properly assessed, and accurate staging of the disease is carried out after the biopsy result is known, and before clinical management is planned.
References:
1. Rosario DJ, Lane JA, Metcalfe C et al. Short term outcomes of prostate biopsy in men tested for cancer by prostate specific antigen: prospective evaluation within the ProtecT study.BMJ 2012;344:d7894.
doi:10.1136/bmj.d7894
2. Djavian B, Rocco B. Optimising prostate biopsy: lack of standardised procedures means that large variations in cancer detection remain. BMJ 2012;344:d8201.
doi:10.1136?bmj.d8201
3. Bastacky SS, Walsh PC, Epstein JI. Needle biopsy associated tumour tracking of adenocarcinoma of the prostate. J Urol 1991; 145 (5): 1003-7.
4. Selley S, Donovan JL, Faulkner A, Coast J, Gillatt D. Diagnosis, management and screening of early localised prostate cancer. Health Technology Assessment 1997; 1(2). www.hta.ac.uk/fullmono/mon102.pdf
5. ProtecT study. Prostate testing for cancer and Treatment. HTA No 96/20/99. Principal investigators: FC Hamdy, JL Donovan, DE Neal . Coordinator: JA Lane.
http://www.hta.ac.uk/project/1230.asp
6. Djavian B, Marihart S. Repeat Prostate Biopsies and the Vienna Nomograms. From Current Clinical Urology: Prostate Biopsy: Indications, Techniques, and Complications (Ed J S Jones); 2008:199-216. Humana Press.
7. Djavian B, Zlotta AR, Remzi M et al. Optimal predictors of prostate cancer in repeat prostate biopsy: a prospective study in 1051 men. J Urol 2000; 163(4): 1144-8.
8. Chun FK-H, Briganti A, Antibi E, Graefen M, Currlin E, Steuber T, et al. Surgical volume is related to the rate of positive surgical margins at radical prostatectomy in European patients. BJU International 2006; 98 (6): 1204-9.
9. Orvieto MA, Alsikafi NF, Shalhav AL, Laven BA, Steinberg GD, Zagaja GP et al. Impact of positive surgical margin status on long-term cancer control after radical prostatectomy. BJU International 2006: 98 (6); 1199-1203.
10. Vickers AJ, Bianco FJ, Serio FM, Eastham JA, Schrag D, Klein EA, et al. The surgical learning curve for prostate cancer control after radical prostatectomy. J Natl Cancer Inst 2007; 99: 1171-7.
11. Touijer K, Kuroiwa K, Eastham JA, Vickers A, Reuter V, Scardino P, et al. Risk-adjusted analysis of prognostic surgical margins following laparoscopic and retropubic radical prostatectomy. European Urology 2007; 52 (4): 1090-6.
12. Stolzenburg J-U, Rabenalt R, Do M, Kallidonis P, Liatsikos EN. Endoscopic extra-peritoneal radical prostatectomy: the University of Leipzig experience of 2000 cases. J Endourology 2008; 22 (10); 2319-26.
13. Yang Y. Treatment of the positive surgical margin following radical prostatectomy. Chinese Medical Journal 2008; 121 (4); 375-9.
14. Yossepowitch O, Bjartell A, Eastham JA, Graefen M, Guillonneau BD, Karakiewicz PI et al. Positive surgical margins in radical prostatectomy: outlining the problem and its long-term consequences. European Urology 2009; 55 (1): 87–99.
15. Viney R, Gommersall L, Zeif J, Hayne D, Shah ZH, Doherty A. Ultrasensitive prostate specific antigen assay following laparoscopic radical prostatectomy – an outcome measure for defining the learning curve. Ann R Coll Surg Engl 2009; 91: 399-403.
Competing interests: Author was invetigated within ProtecT study
Re: Optimising prostate biopsy
I thank Professor Djavan for his comments on the current understanding of the harms associated with prostate biopsies [1]. He does not however reassure me that urologists have considered adequately the safety of multi-needle biopsy with respect to tumour extension, nor does he explain the continuing inaccuracies in staging of local disease extent prior to radical prostatectomy [2].
Professor Djavan refers to two recent studies of morbidity of prostate biopsy [3,4] in which no evidence of tumour seeding or extension were found. However, whereas needle track tumour seeding to the perineum is detectable clinically, extra-capsular tumour extension following trans-rectal biopsy will not be found unless actively investigated, either by imaging techniques or by histological examination of excised prostates following radical surgery. This was not done in either of the studies cited by Professor Djavan and indeed has yet to be done for the multi-needle biopsy techniques that include laterally placed needles. The James Lind Alliance has confirmed this omission, and the safety of laterally placed and laterally directed multi-needle core biopsy was included in their Database of Uncertainties about the Effects of Treatments (DUETs) in 2009 [5].
Whilst acknowledging the limitations of the study by Bastacky et al [6], it is nevertheless the only published investigation of extra-capsular tumour extension following trans-rectal biopsy. The authors warned of the potential risks, particularly in men managed (as in the ProtecT Study) [7] by ‘watchful waiting’. Urologists remain reluctant to accept that multiple needle puncture of the prostate may cause capsular damage releasing sub-capsular tumour, and they consider re-assessment of the capsular boundary after positive biopsy to be unnecessary. To my knowledge, only a single urologist in the UK routinely undertakes a second ultrasound look at the prostatic capsule following positive biopsy. He considers that by doing so he has saved many men (including myself) from unsuccessful radical prostatectomy [Leung H, personal communication 2004].
Laterally placed needles are intended to sample the outer sub-capsular area [8,9] but, with an excursion of 2 cm from the biopsy gun, must have the potential to penetrate through the lateral capsule. Studies such as that of Eastham have demonstrated that positive surgical margins are most commonly found postero-laterally [10]. Recently the NICE Interventional Procedures Committee gave approval for a multi-multi-needle trans-perineal template biopsy (30 to 50 needle cores) with assurances from two urologists that there were no safety issues [11]. Proponents of this technique observe that the associated extra-capsular bleeding creates ‘artifact’ on MRI which may persist for several weeks [12], but potential patients are informed that ‘transperineal biopsies carry no extra risk than a normal prostate biopsy carried out through the rectum [13]. The possibility of tumour extrusion accompanying this extensive bleeding is not considered.
This debate is timely as the NICE Prostate Cancer Guideline 2008(CG58) [14] is under review. As yet there is no indication that the possibility of tumour extension resulting from the biopsy procedure will be considered, and the multi-multi-needle trans-perineal template procedure seems likely to be endorsed.
Sir Liam Donaldson (then Chief Medical Officer) and Sir Michael Richards (National Cancer Director) have agreed with me that the trans-rectal multi-needle prostate biopsy must have the potential to spread tumour outside the capsule, but have found that ‘experts in the diagnosis and treatment of prostate cancer believe that the risk of extra-capsular spread from the use of laterally placed needles is likely to be low or non-existent’ [Donaldson, Richards, personal communications, 2009, 2011]. At a meeting of the Prostate Cancer Advisory Group in October 2011 the theoretical possibility of extra-capsular tumour spread by multi-needle biopsy was at last acknowledged, but there was no support for its investigation, which was perceived as too difficult. The urologists present considered that ‘if tumour extension occurs, someone would have noticed it by now’ [Richards, personal communication 2011].
Professor Djavan asserts that I am ‘a screening adversary trying to identify harms and drawbacks associated with either PSA as a marker or the biopsy by itself’. This is not the case; indeed from personal experience I can endorse the benefits of PSA testing and the necessity of biopsy. However, I feel strongly that improvements in the assessment and management of this disease are long overdue and that men are not fully informed of the potential risks. Urologists have based their opinions about multi-needle biopsy safety on their beliefs, unsupported by evidence of safety, as they have not undertaken any serious investigation of the risks of capsular damage. Is it not time that all harms associated with prostate biopsy are thoroughly and honestly assessed, and every effort made to ensure that men receive the safest possible investigation and treatment?
1. Djavan B. Optimising Prostate Biopsy. BMJ Letter: Authors reply: Evaluation and analysis of complications of prostate needle biopsy.
BMJ 2012;344:e1030
2. Yang Y. Treatment of the positive surgical margin following radical prostatectomy. Chinese Medical Journal 2008;121(4);375-9.
3. Djavan B, Waldert M, Ziotta A, Dobronski P, Seitz C. Remzi M et al. Safety and morbidity of first and repeat trans-rectal ultrasound guided prostate needle biopsies: results of a prospective European prostate cancer detection study. J Urol 2001; 166:856-60.
4. Loeb SJ, van den Heuvel, Zhu X, Bangma CH, Schröder FH, Roobol MJ. Infectious complications and hospital admissions after prostate biopsy in a European randomised trial. Eur Urol 2012: published online 5 January http://www.ncbi.nlm.nih.gov/pubmed/22244150.
5. UK Database of Uncertainties about the Effects of Treatments (DUETs) Specialist Library. Uncertainty: Safety of laterally placed and laterally directed multi-needle core biopsy for diagnosing prostate cancer. Published March 2009.
http://www.library.nhs.uk/DUETs/ViewResource.aspx?resID=310129&tabID=294
6. Bastacky SS, Walsh PC, Epstein JI. Needle biopsy associated tumour tracking of adenocarcinoma of the prostate. J Urol 1991;145(5):1003-7.
7. ProtecT study. Prostate testing for cancer and Treatment. Protocol Version 1, September 2001. Principal Investigators: Hamdy FC, Donovan JL, Neal D. HTA No 90/26/99.
8. Prostate Cancer Risk Management Programme (2006). Undertaking a trans-rectal ultrasound guided biopsy of the prostate. ISBN 9781844630417.
http://www.cancerscreening.nhs.uk/prostate/pcrmp01.pdf
9. NICE Full Guideline. Prostate cancer: diagnosis and treatment (2008) (CG58). National Collaborating Centre for Cancer.
10. Eastham J.A, Kentaro K, Makoto O, Serio AM, Gorbonos A, Norio M et al. Prognostic
significance of location of positive margins in radical prostatectomy specimens (2007). Urol;70(5):965-9.
11. NICE Interventional procedure guidance 364. Transperineal template biopsy and
mapping of the prostate. ISBN 978-1-84936-381-5.
www.nice.org.uk/guidance/IPG364
12 Prostate Mapping Ltd.
www.prostatemapping.com/prostate-biopsy.aspx
13. Prostate Mapping Ltd. Patient Information Sheet
http://www.prostatemapping.com/ProstateMappingPatientInfo.pdf
14. NICE Clinical Guideline and Quality Standard. Prostate Cancer: diagnosis and
treatment (CG58). Draft scope for consultation for Update.
www.nice.org.uk/GuidelinesManual
Competing interests: Author was investigated within the ProtecT Study