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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.

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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 Month: Gleason Grading in the Spotlight

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Every Month the Editor-in-Chief selects an Article of the Month 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 Klaus Brasso, discussing his paper.

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

The impact of the 2005 International Society of Urological Pathology consensus guidelines on Gleason grading – a matched pair analysis

Kasper D. Berg*, Frederik B. Thomsen*, Camilla Nerstrøm*, Martin A. Røder*, Peter
Iversen*, Birgitte G. Toft†, Ben Vainer† and Klaus Brasso*

 

*Department of Urology, Copenhagen Prostate Cancer Center and †Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

 

Read the full article

Objectives

To investigate whether the International Society of Urological Pathology (ISUP) 2005 revision of the Gleason grading system has influenced the risk of biochemical recurrence (BCR) after radical prostatectomy (RP), as the new guideline implies that some prostate cancers previously graded as Gleason score 6 (3 + 3) are now considered as 7 (3 + 4).

Patients and methods

A matched-pair analysis was conducted. In all, 215 patients with Gleason score 6 or 7 (3 + 4) prostate cancer on biopsy who underwent RP before 31 December 2005 (pre-ISUP group), were matched 1:1 by biopsy Gleason score, clinical tumour category, PSA level, and margin status to patients undergoing RP between 1 January 2008 and 31 December 2011 (post-ISUP group). Patients were followed until BCR defined as a PSA level of ≥0.2 ng/mL. Risk of BCR was analysed in a competing-risk model.

JunAOTMResults

Results

The median follow-up was 9.5 years in the pre-ISUP group and 4.8 years in the post-ISUP group. The 5-year cumulative incidences of BCR were 34.0% and 13.9% in the pre-ISUP and post-ISUP groups, respectively (P < 0.001). The difference in cumulative incidence applied to both patients with Gleason score 6 (P < 0.001) and 7 (3 + 4) (P = 0.004). There was no difference in the 5-year cumulative incidence of BCR between patients with pre-ISUP Gleason score 6 and post-ISUP Gleason score 7 (3 + 4) (P = 0.34). In a multiple Cox-proportional hazard regression model, ISUP 2005 grading was a strong prognostic factor for BCR within 5 years of RP (hazard ratio 0.34; 95% confidence interval 0.22–0.54; P < 0.001).

Conclusion

The revision of the Gleason grading system has reduced the risk of BCR after RP in patients with biopsy Gleason score 6 and 7 (3 + 4). This may have consequences when comparing outcomes across studies and historical periods and may affect future treatment recommendations.

Read more articles of the week

Editorial: Current Gleason score 3 + 4 = 7: has it lost its significance compared with its historical counterpart?

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Berg et al. [1] report that patients classified as Gleason score 7 (3 + 4) according to the revised grading system published in 2005 are to some extent similar to patients with pre-2005 Gleason score 6, at least in terms of risk of biochemical recurrence. The logical but not necessarily correct conclusion is that current patients with Gleason score 7 on biopsy are appropriate candidates for active surveillance.

What must be kept in mind is that, using the post-2005 revised grading system, approximately 25% of men with Gleason score 3 + 4 = 7 on biopsy have either 3 + 4 = 7 with tertiary pattern 5 or >4 + 3 = 7 in the corresponding radical prostatectomy [1]. With the exception of men with a limited life expectancy, these men need definitive therapy for their potentially life-threatening cancer. Numerous studies have shown that extended biopsies, whether they are >10- or 12-core, are associated with less upgrading than sextant biopsies [2]. In the report by Berg et al. [1], the median number of cores sampled before 2005 was 6 with an interquartile range (IQR) of 6–6 compared with a median (IQR) of 10 (10–12) cores after 2005. Consequently, in their cohorts, the pre-2005 group of men with Gleason score 3 + 3 = 6 were more likely to have unsampled higher grade cancer and a correspondingly worse prognosis more closely approximating post-2005 better-sampled Gleason score 3 + 4 = 7 cancers.

Berg et al. [1] further claim that the prognostic and clinical value of Gleason score 7 has been weakened since the 2005 modifications. In fact, the revised grading system more accurately reflects prostate cancer biology than the pre-2005 Gleason system. The major consequence of the modification, as Berg et al. [3] illustrate, has been the better prognosis associated with post-2005 Gleason score 6 cancer because patterns associated with more aggressive behaviour have been shifted to Gleason score 7. Historically, a diagnosis of Gleason score 6 cancer, even at radical prostatectomy, was not as predictive of ‘good’ behaviour, and had a higher rate of progression with some men even dying from prostate cancer [4]. Currently, Gleason score 6 cancer at radical prostatectomy has a 96% cure rate at 5 years, even including cases with extraprostatic extension and positive margins [3]. Several studies have shown that post-2005 pure Gleason score 6 cancers at radical prostatectomy are incapable of metastasizing to lymph nodes [4]. Berg et al. are correct, however, that men with a post-2005 grade of Gleason Score 3 + 4 = 7 have a better prognosis than those graded prior to 2005. As a consequence, it has been recommended that pathologists should record the percent pattern 4 in cases with Gleason score 7 on biopsy for men being considered for active surveillance [5]. For the appropriate patient, depending on age, comorbidity, extent of cancer, MRI findings, patient desire, etc., could be a candidate for active surveillance with Gleason score 3 + 4 = 7 if the pattern 4 is limited. Currently, this information is not transparent in most pathology reports.

A new grading system, first proposed in BJUI by this author, and verified in a large multi-institutional study, resulted in a simplified five-grade group system that more accurately reflects the biology of prostate cancer than the pre-2005 grading system [3, 6]. Men with Gleason score 6 cancers need to be reassured that their cancer is the lowest grade that is currently assigned, despite Gleason scores ranging from 2 to 10. In addition, I have talked to some patients with Gleason score 3 + 4 = 7 who think that they are going to die in the near future because their score of 7 was closer to highest grade of 10 than the lowest grade of 2. With the new grading system, patients can be reassured that they have a Grade group 1 (3 + 3 = 6) out of 5, which is the lowest grade, or a Grade group 2 (Gleason score 3 + 4 = 7) out of 5, which is still a relatively low grade.

Read the full article
Jonathan I. Epstein
Departments of Pathology, Urology and Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA

 

References

 

1 Berg KD, Thomsen FB, Nerstrom C et al. The impact of the 2005 International Society of Urological Pathology consensus guidelines on Gleason grading – a matched pair analysis. BJU Int 2016; 117: 883–9

 

2 Epstein JI, Feng Z, Trock BJ , Pierorazio PM. Upgrading and downgrading of prostate cancer from biopsy to radical prostatectomy: incidence and predictive factors using the modified Gleason grading system and factoring in tertiary grades. Eur Urol 2012; 61: 1019–24

 

3 Epstein JI, Zelefsky MJ, Sjoberg DD et al. A contemporary prostate cancer grading system: a validated alternative to Gleason score. Eur Urol 2016; 69: 428–35

 

4 RossHM, Kryvenko ON, Cowan JE, Simko JP, Wheeler TM, Epstein JI. Do adenocarcinomas of the prostate with Gleason score (GS) ≤ 6have the potential to metastasize to lymph nodes? Am J Surg Pathol 2012; 36: 1346–52

 

5 Kryvenko ON, Epstein JI. Prostate cancer grading: a decade after the 2005 modified Gleason grading system. Arch Pathol Lab Med 2016; [Epub ahead of print]

 

6 Pierorazio PM, Walsh PW, Partin AW, Epstein JI. Prognostic Gleason grade grouping: data based on the modified Gleason scoring system. BJU Int 2013; 111: 753–60

 

Video: Gleason Grading in the Spotlight

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The impact of the 2005 International Society of Urological Pathology consensus guidelines on Gleason grading – a matched pair analysis

Kasper D. Berg*, Frederik B. Thomsen*, Camilla Nerstrøm*, Martin A. Røder*, Peter Iversen*, Birgitte G. Toft†, Ben Vainer† and Klaus Brasso*

 

*Department of Urology, Copenhagen Prostate Cancer Center and †Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

 

Read the full article

Objectives

To investigate whether the International Society of Urological Pathology (ISUP) 2005 revision of the Gleason grading system has influenced the risk of biochemical recurrence (BCR) after radical prostatectomy (RP), as the new guideline implies that some prostate cancers previously graded as Gleason score 6 (3 + 3) are now considered as 7 (3 + 4).

Patients and methods

A matched-pair analysis was conducted. In all, 215 patients with Gleason score 6 or 7 (3 + 4) prostate cancer on biopsy who underwent RP before 31 December 2005 (pre-ISUP group), were matched 1:1 by biopsy Gleason score, clinical tumour category, PSA level, and margin status to patients undergoing RP between 1 January 2008 and 31 December 2011 (post-ISUP group). Patients were followed until BCR defined as a PSA level of ≥0.2 ng/mL. Risk of BCR was analysed in a competing-risk model.

JunAOTMResults

Results

The median follow-up was 9.5 years in the pre-ISUP group and 4.8 years in the post-ISUP group. The 5-year cumulative incidences of BCR were 34.0% and 13.9% in the pre-ISUP and post-ISUP groups, respectively (P < 0.001). The difference in cumulative incidence applied to both patients with Gleason score 6 (P < 0.001) and 7 (3 + 4) (P = 0.004). There was no difference in the 5-year cumulative incidence of BCR between patients with pre-ISUP Gleason score 6 and post-ISUP Gleason score 7 (3 + 4) (P = 0.34). In a multiple Cox-proportional hazard regression model, ISUP 2005 grading was a strong prognostic factor for BCR within 5 years of RP (hazard ratio 0.34; 95% confidence interval 0.22–0.54; P < 0.001).

Conclusion

The revision of the Gleason grading system has reduced the risk of BCR after RP in patients with biopsy Gleason score 6 and 7 (3 + 4). This may have consequences when comparing outcomes across studies and historical periods and may affect future treatment recommendations.

Read more articles of the week
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