Ben Adams has rightly celebrated the achievements of ‘the ten pioneers of transparency’ in obtaining changes to European Union Clinical Trials Regulations so that relevant trials’ clinical study reports will now be published (BMJ 2015;350:g7717). Now, there is the expectation that ‘within two years the public and researchers will be able to read, in full, clinical study reports for all newly approved drug trials, whether conducted by industry or academia.’ However, it is to be noticed that this ‘watershed moment for clinical trial transparency’ will only apply to ‘newly approved drug trials’ – so trials and studies relating to medical and surgical investigations, and treatments of patients in the clinical situation, are not included.
In their recent observational study of surgical randomised controlled trials Chapman and colleagues report that ‘one in five randomised controlled trials are discontinued early, one in three completed trials remain unpublished, and investigators of unpublished studies are frequently not contactable’ (BMJ 2014;349:g6870). Ioannidis has also commented that too many surgical trials are ‘unregistered, unfinished, unpublished, unreachable, or simply irrelevant’ (BMJ 2014;349:g7089). In Editor’s Choice (BMJ 2015;350:g7811) the increase in data transparency for drug trials was welcomed, but it was accepted that there is still ‘much to be done before we can really trust the evidence base for clinical decisions.’
For the past 14 years, following my own experience when investigated for prostate cancer, and learning that a multi-needle biopsy had caused extra-capsular extension of my tumour tissue, I have tried to suggest to urologists that it should be openly recognised that multi-needle systematic prostate biopsy has an inevitable potential to cause early intra-capsular tumour tissue to be extended outside the capsule. I have received support for my concern from many professional colleagues, but urologists insist that prostate cancer is different from all other malignancies, requires a systematic biopsy procedure of the whole gland for diagnosis, and they remain convinced that the tumour is never locally spread as a result of needle puncture – even though the initial 6-needle procedure of the early 1990’s has progressed to as many as 50 or even 60 needle cores.
When compiling the NICE Prostate Cancer Guideline (2008)1 and its Update (2014) the responsible Guideline Development Groups were unable to consider the safety of such multi-needle biopsies as there was/is little published evidence to suggest that biopsy related tumour extension occurs, and it has not been investigated. Recently, after raising my biopsy safety concerns with NHS England the National Clinical Director for Cancer, Mr Sean Duffy, was able to tell me that ‘it is a difficult issue, but one where our clinical advisers feel that the risk of extra-capsular spread is very low or non-existent.’ (Personal communication, 15.12.14).
The National Prostate Cancer Audit Document was published in November 2014.2 Multi-needle systematic biopsy procedures are approved and recommended, and assessment of the prostate capsular margin and the local extent of tumour tissue by MP-MRI scan is suggested either before or after biopsy. Only one result can be reported, so if scans are done both before and after the biopsy any comparison and assessment of its possible effect on local tumour extent is not collected as part of the Audit. Version 2 of the Audit Documentation, published on 17th December3, recommends that for all men all planned prostate cancer treatments as agreed with the patient must be recorded for the Audit before their treatment begins. But, if men are to specifically agree to their treatment programme, as is normal and accepted practice, then they need to be fully informed about all potential risks and harms as well as the possible benefits. Yet, they are not warned that there is an inevitable risk of extensive systematic biopsy procedures causing local tumour extension, the Audit protocol does not recognise that multi-multi-needle biopsy has such a potential, and it is clear that there is no intention to assess whether or not it occurs.
If patient safety is be ‘always and truly paramount for the NHS’ I submit that the safety of multi-needle prostate biopsy needs to be urgently investigated, always considered during present every day clinical care, and investigated in all trials assessing the results of prostate cancer treatment and management. Sadly, it was not included in the protocol of the ProtecT Study4, nor in its ProBE sub-study that was supposedly recording all adverse events following biopsy5.
NHS England has now announced that patients are to have the option to refer themselves for diagnostic tests as part of an early diagnostic programme for cancer (BMJ 2015;350:h185). May I suggest that if a man requests a PSA test and found to have an elevated level and the subsequent prostate biopsy result is positive, he should then ensure that the capsular margin of his prostate has been carefully scanned, and local tumour extent re-assessed after the biopsy, before agreeing to his advised planned treatment.
G. David Stainsby FRCS (England)
Retired Consultant Orthopaedic surgeon
Newcastle upon Tyne
1. NICE Full Guideline. Prostate cancer: diagnosis and treatment (2008), (CG 58). National Collaborating Centre for Cancer. doi: http://www.nice.org.uk/nicemedia/pdf/CG58FullGuideline.pdf
2. National Prostate Cancer Audit: Guidance and Data Dictionary Version 1; 17th July and 14th November 2014. http://www.npca.org.uk/wp-content/uploads/2014/07/NPCA_FAQs_Version-1.0_...
3. National Prostate Cancer Audit. Guidance and Data Dictionary: Version 2.0–17th December 2014. http://www.npca.org.uk/wp-content/uploads/2013/07/NPCA_MDS-guidance-data...
4. ProtecT study (Prostate testing for cancer and Treatment). Protocol v 2.2, June 2005. ISRCTN20141297: HTA No 96/20/99. Principal Investigators: Hamdy FC, Donovan JL, Neal DE. Trial Coordinator: Jane JA.
5. Rosario DJ, Lane JA, Metcalfe C et al. Short term outcomes of prostate biopsy in men tested by prostate specific antigen: prospective evaluation within the Protect study. BMJ 2012;344:d7894.
Competing interests: No competing interests