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Article of the Week: TRUS-Guided RB PCa Detection – Reasons for Targeted Biopsy Failure

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Every Week the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from Hannes Cash and Patrick Asbach, discussing their paper.

If you only have time to read one article this week, it should be this one.

Prostate cancer detection on transrectal ultrasonography-guided random biopsy despite negative real-time magnetic resonance imaging/ultrasonography fusion-guided targeted biopsy: reasons for targeted biopsy failure

Hannes Cash*, Karsten Gunzel*, Andreas Maxeiner*, Carsten Stephan*, Thomas Fischer†, Tahir Durmus†, Kurt Miller*, Patrick Asbach†, Matthias Haas† and Carsten Kempkensteffen*

 

*Department of Urology, and †Department of Radiology, Charite–University of Medicine Berlin, Berlin, Germany M. H. and C.K. contributed equally to the study.

 

Read the full article

Objective

To examine the value of additional transrectal ultrasonography (TRUS)-guided random biopsy (RB) in patients with negative magnetic resonance imaging (MRI)/ultrasonography (US) fusion-guided targeted biopsy (TB) and to identify possible reasons for TB failure.

Patients and Methods

We conducted a subgroup analysis of 61 men with prostate cancer (PCa) detected by 10-core RB but with a negative TB, from a cohort of 408 men with suspicious multiparametric magnetic resonance imaging (mpMRI) between January 2012 and January 2015. A consensus re-reading of mpMRI results (using Prostate Imaging Reporting and Data System [PI-RADS] versions 1 and 2) for each suspicious lesion was performed, with the image reader blinded to the biopsy results, followed by an unblinded anatomical correlation of the lesion on mpMRI to the biopsy result. The potential reasons for TB failure were estimated for each lesion. We defined clinically significant PCa according to the Epstein criteria and stratified patients into risk groups according to the European Association of Urology guidelines.

JulAOTW3Results

Results

Our analysis showed that RB detected significant PCa in 64% of patients (39/61) and intermediate-/high-risk PCa in 57% of patients (35/61). The initial mpMRI reading identified 90 suspicious lesions in the cohort. Blinded consensus re-reading of the mpMRI led to PI-RADS score downgrading of 45 lesions (50%) and upgrading of 13 lesions (14%); thus, negative TB could be explained by falsely high initial PI-RADS scores for 32 lesions (34%) and sampling of the target lesion by RB in the corresponding anatomical site for 36 out of 90 lesions (40%) in 35 of 61 patients (57%). Sampling of the target lesion by RB was most likely for lesions with PI-RADS scores of 4/5 and Gleason scores (GS) of ≥7. A total of 70 PCa lesions (67% with GS 6) in 44 patients (72%) were sampled from prostatic sites with no abnormalities on mpMRI.

Conclusion

In cases of TB failure, RB still detected a high rate of significant PCa. The main reason for a negative TB was a TB error, compensated for by positive sampling of the target lesion by the additional RB, and the second reason for TB failure was a falsely high initial PI-RADS score. The challenges that arise for both MRI diagnostics and prostate lesion sampling are evident in our data and support the integration of RB into the TB workflow.

Read more articles of the week

Editorial: MRI-Fusion Biopsy – Behind the Scenes

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MRI information of the prostate is increasingly used for improving the diagnostic yield of prostate biopsies [1]. However, increasing complexity of a procedure makes it prone to errors at multiple technical and human levels. Incorporating MRI information and ultrasonography (US) images for MRI-fusion biopsies is a technically challenging task. It involves various steps such as the acquisition and fusion of MRI and US images, the needle guidance during biopsy, and the diligence of the pathological evaluation of biopsy specimens. These different steps and interfaces between different medical professions influence the diagnostic performance of MRI-fusion biopsies.

For example, in daily clinical practice, MRIs from different institutions still harbour a great variance of sequences and reporting, despite the European Society of Urogenital Urology (ESUR) recently introducing acquisition and imaging protocols and a new and advanced version of the Prostate Imaging Reporting and Data System (PIRADS) version 2.0 [2]. The usefulness of such reporting schemes is evidenced by a moderate-to-good interobserver agreement between uro-radiologists for tumour lesion interpretation and corresponding κ values ranging from 0.55 to 0.80 [3]. Important pitfalls of image interpretation are benign lesions such as prostatitis, BPH and fibrosis, which might score similarly to prostate cancer lesions. This problem is further aggravated by a high proportion of patients that receive their first multiparametric MRI (mpMRI) of the prostate in the repeat-biopsy setting with a high burden of post-biopsy artefacts (haemorrhage, capsular irregularity) and lower overall cancer detection rate. Also, during MRI-fusion biopsy patient movement, prostate deformation by the US probe, and mismatch of image planes can lead to a biopsy error exceeding 4 mm. Moreover, targeting error might be aggravated by MRI underestimation of the tumour volume compared with final pathology [4]. After various authors reported the advantages and accuracy of MRI/US-fusion biopsy approaches, Cash et al. [5] address potential reasons for targeted biopsy failure to detect prostate cancer compared with random biopsy. Within their analyses the authors address potential limitations and technical considerations. Based on different technical biopsy strategies (with the patient placed within the MRI scanner (‘in-bore’) vs outside) and different technical approaches, these considerations are very important.

In contrast to cognitive fusion, most MRI/US platforms allow needle tracking by archiving the needle orientation, either by an electromagnetic, image-based or stepper-based mechanism [1]. However, lesion targeting by needle guidance is highly dependent on the dimensions of the primary lesion, numbers of relevant lesions, localisation, and overall prostate volume, making MRI-US fusion and cognitive fusion more error prone (i.e. aiming off the mark with the needle) than in-bore biopsies. Moreover, different technical fusion approaches provide different degrees of manual/automated adjustment tools, with for example either rigid or elastic image transformation to facilitate MRI/US image alignment.

Finally, due to the recent introduction of these techniques the influence of learning curve and experience of the uro-radiologist must be considered [6].

In their analyses, Cash et al. [5] found that 34% of negative targeted biopsies could be explained by initially too high estimated PIRADS scores that were downgraded at re-reading. Interestingly, the remaining lesions were without an mpMRI correlate but within this group 92.9% showed a primary Gleason 3 pattern in biopsy pathology, suggesting a high degree of invisibility on mpMRI. Subanalyses did not show an association of targeted biopsy failures in the ventral location. Therefore, the study by Cash et al. [5] is an important precursor for further analyses to address other underlying reasons for targeted biopsy failure. Moreover, it reveals the need for a tight collaboration of radiologists, urologists, and pathologists as interdisciplinary partners involved in MRI-fusion biopsy. Consequently, the optimal diagnostic performance of MRI-fusion biopsies can only be achieved through standardised MRI performance, reading and reporting of MRI findings, as well as final correlation of MRI findings with histopathological work up.

Read the full article
Lars Budaus and Sami-Ramzi Leyh-Bannurah
Martini-Clinic University Hospital Hamburg-Eppendorf, Hamburg, Germany

 

References

 

1 Logan JK, Rais-Bahrami S, Turkbey B et al. Current status of magnetic resonance imaging (MRI) and ultrasonography fusion software platforms for guidance of prostate biopsies. BJU Int 2014;114:641–52

 

2 American College of Radiology. Prostate Imaging Reporting and Data System (PI-RADS), version 2.0. 2015. Available at: https://www.acr.org/ Quality-Safety/Resources/PIRADS/. Accessed November 2015

 

3 Schimmoller L, Quentin M, Arsov C et al. Inter-reader agreement of the ESUR score for prostate MRI using in-bore MRI-guided biopsies as the reference standard. Eur Radiol 2013;23:3185–90

 

4 Rud E, Klotz D, Rennesund K et al. Detection of the index tumour and tumour volume in prostate cancer using T2-weighted and diffusion-weighted magnetic resonance imaging (MRI) alone. BJU Int 2014;114: E32–42

 

5 Cash H, Gunzel K, Maxeiner A et al. Prostate cancer detection on transrectal ultrasonography-guided random biopsy despite negative real- time magnetic resonance imaging/ultrasonography fusion-guided targeted biopsy: reasons for targeted biopsy failure. BJU Int 2016; 118: 35–43

 

6 Gaziev G, Wadhwa K, Barrett T et al. Defining the learning curve for multiparametric magnetic resonance imaging (MRI) of the prostate using MRI-transrectal ultrasonography (TRUS) fusion-guided transperineal prostate biopsies as a validation tool. BJU Int 2016; 117: 80–6

 

Video: TRUS-Guided RB Prostate Cancer Detection – Reasons for Targeted Biopsy Failure

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Prostate cancer detection on transrectal ultrasonography-guided random biopsy despite negative real-time magnetic resonance imaging/ultrasonography fusion-guided targeted biopsy: reasons for targeted biopsy failure

Hannes Cash*, Karsten Gunzel*, Andreas Maxeiner*, Carsten Stephan*, Thomas Fischer†, Tahir Durmus†, Kurt Miller*, Patrick Asbach†, Matthias Haas† and Carsten Kempkensteffen*

 

*Department of Urology, and †Department of Radiology, Charite–University of Medicine Berlin, Berlin, Germany M. H. and C.K. contributed equally to the study.

 

Read the full article

Objective

To examine the value of additional transrectal ultrasonography (TRUS)-guided random biopsy (RB) in patients with negative magnetic resonance imaging (MRI)/ultrasonography (US) fusion-guided targeted biopsy (TB) and to identify possible reasons for TB failure.

Patients and Methods

We conducted a subgroup analysis of 61 men with prostate cancer (PCa) detected by 10-core RB but with a negative TB, from a cohort of 408 men with suspicious multiparametric magnetic resonance imaging (mpMRI) between January 2012 and January 2015. A consensus re-reading of mpMRI results (using Prostate Imaging Reporting and Data System [PI-RADS] versions 1 and 2) for each suspicious lesion was performed, with the image reader blinded to the biopsy results, followed by an unblinded anatomical correlation of the lesion on mpMRI to the biopsy result. The potential reasons for TB failure were estimated for each lesion. We defined clinically significant PCa according to the Epstein criteria and stratified patients into risk groups according to the European Association of Urology guidelines.

JulAOTW3Results

Results

Our analysis showed that RB detected significant PCa in 64% of patients (39/61) and intermediate-/high-risk PCa in 57% of patients (35/61). The initial mpMRI reading identified 90 suspicious lesions in the cohort. Blinded consensus re-reading of the mpMRI led to PI-RADS score downgrading of 45 lesions (50%) and upgrading of 13 lesions (14%); thus, negative TB could be explained by falsely high initial PI-RADS scores for 32 lesions (34%) and sampling of the target lesion by RB in the corresponding anatomical site for 36 out of 90 lesions (40%) in 35 of 61 patients (57%). Sampling of the target lesion by RB was most likely for lesions with PI-RADS scores of 4/5 and Gleason scores (GS) of ≥7. A total of 70 PCa lesions (67% with GS 6) in 44 patients (72%) were sampled from prostatic sites with no abnormalities on mpMRI.

Conclusion

In cases of TB failure, RB still detected a high rate of significant PCa. The main reason for a negative TB was a TB error, compensated for by positive sampling of the target lesion by the additional RB, and the second reason for TB failure was a falsely high initial PI-RADS score. The challenges that arise for both MRI diagnostics and prostate lesion sampling are evident in our data and support the integration of RB into the TB workflow.

Read more articles of the week

Article of the Week: DSNB for Penile Cancer

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Every Week the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

 

Dynamic sentinel lymph node biopsy for penile cancer: a comparison between 1- and 2-day protocols

Panagiotis Dimopoulos*, Panagiotis Christopoulos*, Sam Shilito†, Zara Gall*‡, Brian Murby§, David Ashworth§, Ben Taylor, Bernadette Carrington, Jonathan Shanks**, Noel Clarke*, Vijay Ramani*, Nigel Parr*, Maurice Lau* and Vijay Sangar*

 

Departments of *Urology, §Nuclear Medicine, Radiology , **Pathology, The Christie Hospital, Manchester, †Medical School, University of Manchester, Manchester, and ‡Department of Urology, Royal Bolton Hospital, Bolton Lancashire, UK
Read the full article

Objective

To determine the outcome of clinically negative node (cN0) patients with penile cancer undergoing dynamic sentinel node biopsy (DSNB), comparing the results of a 1- and 2-day protocol that can be used as a minimal invasive procedure for staging of penile cancer.

Patients and Methods

This is a retrospective analysis of 151 cN0 patients who underwent DSNB from 2008 to 2013 for newly diagnosed penile cancer. Data were analysed per groin and separated into groups according to the protocol followed. The comparison of the two protocols involved the number of nodes excised, γ-counts, false-negative rates (FNR), and complication rates (Clavien–Dindo grading system).

JuneAOTW3

Results

In all, 280 groins from 151 patients underwent DSNB after a negative ultrasound ± fine-needle aspiration cytology. The 1-day protocol was performed in 65 groins and the 2-day protocol in 215. Statistically significantly more nodes were harvested with the 1-day protocol (1.92/groin) compared with the 2-day protocol (1.60/groin). The FNRs were 0%, 6.8% and 5.1%, for the 1-day protocol, 2-day protocol, and overall, respectively. Morbidity of the DSNB was 21.4% for all groins, and 26.2% and 20.1% for the 1-day and 2-day protocols, respectively. Most of the complications were of Clavien–Dindo Grade 1–2.

Conclusions

DSNB is safe for staging patients with penile cancer. There is a trend towards a 1-day protocol having a lower FNR than a 2-day protocol, albeit at the expense of a slightly higher complication rate.

Read more articles of the week

Article of the Week: Be Clear on Cancer – Blood in Pee

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Every Week the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from Mr. Archie Hughes-Hallett,, discussing his paper.

If you only have time to read one article this week, it should be this one.

Assessing the impact of mass media public health campaigns. ‘Be Clear on Cancer: Blood in Pee’ a case in point

Archie Hughes-Hallett*, Daisy Browne†, Elsie Mensah*, Justin Vale*† and Erik Mayer*†‡

 

*Department of Surgery and Cancer, Imperial College London, †Department of Urology, Imperial College Healthcare Trust, and ‡Institute of Global Health Innovation, Imperial College London, London, UK

 

Read the full article

Objectives

To assess the impact on suspected cancer referral burden and new cancer diagnosis of Public Health England’s recent Be Clear on Cancer ‘blood in pee’ mass media campaign.

Methods

A retrospective cohort study design was used. For two distinct time periods, August 2012 to May 2013 and August 2013 to May 2014, all referrals of patients deemed to be at risk of urological cancer by the referring primary healthcare physician to Imperial College NHS Healthcare Trust were screened. Data were collected on age and sex and whether the referral was for visible haematuria, non-visible haematuria or other suspected urological cancer. In addition to referral data, hospital episode data for all new renal cell (RCC) and upper and lower tract transitional cell carcinoma (TCC), as well as testicular and prostate cancer diagnoses for the same time periods were obtained.

Results

Over the campaign period and the subsequent 3 months, the number of haematuria referrals increased by 92% (P = 0.013) when compared with the same period a year earlier. This increase in referrals was not associated with a significant corresponding rise in cancer diagnosis; instead changes of 26.8% (P = 0.56) and −3.3% (P = 0.84) were seen in RCC and TCC, respectively.

AOTW2Apr

 

Conclusions

This study has shown that the Be Clear on Cancer ‘blood in pee’ mass media campaign significantly increased the number of new suspected cancer referrals, but there was no significant change in the diagnosis of target cancers across a large catchment. Mass media campaigns are expensive, require significant planning and appropriate implementation and, while the findings of this study do not challenge their fundamental objective, more work needs to be done to understand why no significant change in target cancers was observed. Further consideration should also be given to the increased referral burden that results from these campaigns, such that pre-emptive strategies, including educational and process mapping, across primary and secondary care can be implemented.

Read more articles of the week

Editorial: Be better with public health campaigns (and taxpayers’ money)

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In this month’s issue of the BJUI, Hughes-Hallette et al. [1] report on the impact of a mass media public health campaign for gross haematuria. The authors performed a retrospective analysis evaluating the effectiveness of the ‘Be Clear on Cancer: “Blood in the pee”’ campaign. Similar campaigns for colorectal cancer have shown increased referrals and cost, without increasing the number of cancer diagnoses [2, 3]. In the current study [1], cancer diagnosis similarly did not rise. The two questions that therefore needs to be asked are:

  1. Is gross i.e. visible haematuria a predictor for urological malignancy?
  2. Does a mass media public health campaign constitue an effective means of improving early diagnosis of cancer?

Recent data from large integrative datasets have shown that visible haematuria is a significant predictor for bladder cancer [4, 5]. If gross haematuria is a predictor for urological malignancy, however, why did the authors [1] fail to find an increase in diagnosis of urological malignancy in their study? While the authors indicate that the study may have been underpowered, and that the use of an unlinked dataset may have interfered with proper accounting of cancer incidence, one must also consider that mass media outreach may not be an effective method for cancer outreach.

The ‘Be Clear on Cancer’ campaign involved the use of television adverts, print media and ‘out of home’ advertisements. Using this method, patients who are at risk of renal and bladder cancer, i.e. men, those aged >50 years, and smokers, are targeted as frequently as non-smoking teenagers. This type of mass media outreach programme is analogous to traditional advertising, where the message is often diluted and ineffective. While the ‘Be Clear on Cancer’ campaign is a worthy endeavour, the data do not seem to support the use of taxpayers’ money given its ineffective nature. A novel approach to visible haematuria may be to encourage GPs to ask patients about visible, painless haematuria, much as they would ask about chest pain or blood pressure. This would create a more focussed and durable outreach programme that would reduce the number of non-oncological referrals. As stewards of taxpayers’ money, we must be careful of how public funds are spent. The next generation of mass media outreach may require a combination of traditional media in addition to, social media and targeted advertising [6]. Although the ‘Be Clear on Cancer’ campaign did not appear to achieve its intended goals at this time, we must continue to refine and create new interactive approaches to improve the diagnosis and treatment of urological malignancies.

Read the full article
Casey K. Ng
Department of Urology, Southern California Permanente Medical Group, Pasadena, and USC Institute of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

 

References

 

1 Hughes-Hallett A, Browne D, Mensah E, Vale J, Mayer E. Assessing the impact of mass media public health campaigns. Be Clear on Cancer ‘blood in pee’: a case in point. BJU Int 2016; 117: 570–75

 

2 Peacock O, Clayton S, Atkinson F, Tierney GM, Lund JN. ‘Be Clear on Cancer’: the impact of the UK National Bowel Cancer Awareness Campaign. Colorectal Dis 2013; 15: 963–7

 

3 Bethune R, Marshall MJ, Mitchell SJ et al. Did the ‘Be Clear on Bowel Cancer’ public awareness campaign pilot result in a higher rate of cancer detection? Postgrad Med J 2013; 89: 390–3

 

4 Jung H, Gleason JM, Loo RK, Patel HS, Slezak JM, Jacobsen SJ. Association of hematuria on microscopic urinalysis and risk of urinary tract cancer. J Urol 2011; 185: 1698–703

 

5 Loo RK, Lieberman SF, Slezak JM et al. Stratifying risk of urinary tract malignant tumors in patients with asymptomatic microscopic hematuria. Mayo Clin Proc 2013; 88: 129–38

 

6 Freeman B, Potente S, Rock V, McIver J. Social media campaigns that make a difference: what can public health learn from the corporate sector and other social change marketers? Public Health Res Pract 2015; 25: e2521517

 

Video: Be Clear on Cancer – Blood in Pee

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Assessing the impact of mass media public health campaigns. ‘Be Clear on Cancer: Blood in Pee’ a case in point

Archie Hughes-Hallett*, Daisy Browne†, Elsie Mensah*, Justin Vale*† and Erik Mayer*†‡

 

*Department of Surgery and Cancer, Imperial College London, †Department of Urology, Imperial College Healthcare Trust, and ‡Institute of Global Health Innovation, Imperial College London, London, UK

 

Read the full article

Objectives

To assess the impact on suspected cancer referral burden and new cancer diagnosis of Public Health England’s recent Be Clear on Cancer ‘blood in pee’ mass media campaign.

Methods

A retrospective cohort study design was used. For two distinct time periods, August 2012 to May 2013 and August 2013 to May 2014, all referrals of patients deemed to be at risk of urological cancer by the referring primary healthcare physician to Imperial College NHS Healthcare Trust were screened. Data were collected on age and sex and whether the referral was for visible haematuria, non-visible haematuria or other suspected urological cancer. In addition to referral data, hospital episode data for all new renal cell (RCC) and upper and lower tract transitional cell carcinoma (TCC), as well as testicular and prostate cancer diagnoses for the same time periods were obtained.

Results

Over the campaign period and the subsequent 3 months, the number of haematuria referrals increased by 92% (P = 0.013) when compared with the same period a year earlier. This increase in referrals was not associated with a significant corresponding rise in cancer diagnosis; instead changes of 26.8% (P = 0.56) and −3.3% (P = 0.84) were seen in RCC and TCC, respectively.

AOTW2Apr

Conclusions

This study has shown that the Be Clear on Cancer ‘blood in pee’ mass media campaign significantly increased the number of new suspected cancer referrals, but there was no significant change in the diagnosis of target cancers across a large catchment. Mass media campaigns are expensive, require significant planning and appropriate implementation and, while the findings of this study do not challenge their fundamental objective, more work needs to be done to understand why no significant change in target cancers was observed. Further consideration should also be given to the increased referral burden that results from these campaigns, such that pre-emptive strategies, including educational and process mapping, across primary and secondary care can be implemented.

Read more articles of the week
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