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Editorial: Can systematic biopsy be safely avoided at the time of MRI/ultrasonography fusion biopsy?

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In clinical practice, the need for maximising prostate cancer detection is often balanced against the theoretical risks of infection, bleeding, and pain associated with taking additional cores. In this novel study, Sathianathen et al. [1] provide a tool for measuring the oncological benefit of including concurrent systematic biopsy (SB) at the time of MRI‐guided targeted biopsy (TB). There were several key findings: (i) Amongst patients undergoing MRI‐guided biopsy (all biopsy settings), 11.6% were found to have significant cancers detected by SB alone; (ii) Amongst patients who had clinically significant cancers detected by SB alone, 52.2% were sampled within sextants outside the targeted regions of interest; (iii) According to the proposed nomogram, patients with prior negative biopsies, fewer MRI lesions, and lower Prostate Imaging‐Reporting and Data System (PI‐RADS) scores were at the lowest risk of missing significant cancer when SB was omitted.

Based on the present study, biopsy setting appears to be a key factor for deciding whether to omit SB. In the subset of patients undergoing primary biopsy, the authors found that 18.5% of cancers were detected by SB alone. These results are consistent with those of the MRI‐FIRST trial, which showed 14% of cancers were detected by SB only, 20% by TB only, and 66% by combining both techniques [2]. MRI‐FIRST concluded that in the primary biopsy setting, there was no difference between SB and TB in detection of clinically significant prostate cancer, although combining both techniques provided the highest detection rate.

Prior negative biopsy cohorts are generally at lower risk of harbouring significant cancer, as many cancers have already been ‘selected out’ by initial biopsies. In this setting, TB plays an important role in sampling tumour foci in difficult‐to‐reach regions of the prostate (e.g., anterior and apical) [3]. According to the authors’ nomogram, prior negative biopsy patients were least likely to benefit from concurrent SB. While the authors suggest a paradigm of selectively omitting SB, some authors have proposed omitting both TB and SB altogether in select patients. A previously reported multi‐institutional nomogram can be used to predict benign pathology after MRI‐guided biopsy, which can help reduce the number of unnecessary biopsies after MRI in the prior negative biopsy setting [4]. This clinical tool was further externally validated and optimised by Bjurlin et al. [5].

The ‘active surveillance (AS)’ setting typically refers to a confirmatory MRI‐guided biopsy in men with Grade Group 1 prostate cancer prior to enrollment in AS. Recently, the presence of cribriform morphology in Grade Group 2 patients was confirmed to be a key poor prognostic feature that would exclude patients from AS [6]. The present study, however, did not account for different Gleason pattern 4 morphologies in their analysis, as ‘significant cancer’ was defined by Grade Group alone. Studies by independent groups have found that TB combined with SB was more accurate than either modality alone for detecting cribriform at the time of MRI‐guided biopsy [7, 8]. Therefore, concurrent SB is required to properly sample cribriform cancers in patients who are considering AS.

In this study, Sathianathen et al. [1] provide clinicians with a clinical tool for quantifying the added oncological value of concurrent SB. However, concurrent SB is probably prudent for most patients, particularly for those considering AS or focal therapy for which accurate determination of whole gland grade, cancer volume, and cribriform status are essential. As reducing the number of cores has not yet been shown to reduce biopsy‐related complications, are we willing to suboptimise cancer sampling without proven compensation?

by Matthew Truong

References

  1. Sathianathen, NJ, Warlick, CA, Weight, CJ et al. A clinical prediction tool to determine the need for concurrent systematic sampling at the time of magnetic resonance imaging‐guided biopsy. BJU 2019; 123: 612– 7
  3. 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 Int 2015; 115: 562– 70
  4. Truong, M, Wang, B, Gordetsky, JB et al. Multi‐institutional nomogram predicting benign prostate pathology on magnetic resonance/ultrasound fusion biopsy in men with a prior negative 12‐core systematic biopsy. Cancer 2018; 124: 278– 85
  5. Bjurlin, MA, Renson, A, Rais‐Bahrami, S et al. Predicting benign prostate pathology on magnetic resonance imaging/ultrasound fusion biopsy in men with a prior negative 12‐core systematic biopsy: external validation of a prognostic nomogram. Eur Urol Focus 2018. [Epub ahead of print] https://doi.org/10.1016/j.euf.2018.05.005
  6. Kweldam, CF, Kümmerlin, IP, Nieboer, D et al. Presence of invasive cribriform or intraductal growth at biopsy outperforms percentage grade 4 in predicting outcome of Gleason score 3+4=7 prostate cancer. Mod Pathol 2017; 30: 1126– 32
  7. Truong, M, Feng, C, Hollenberg, G et al. A comprehensive analysis of cribriform morphology on magnetic resonance imaging/ultrasound fusion biopsy correlated with radical prostatectomy specimens. J Urol 2018; 199: 106– 13
  8. Prendeville, S, Gertner, M, Maganti, M et al. Role of magnetic resonance imaging targeted biopsy in detection of prostate cancer harboring adverse pathological features of intraductal carcinoma and invasive cribriform carcinoma. J Urol 2018; 200: 104– 13

 

 

Article of the month: Prostate cancer mortality rates in Peru and its geographical regions

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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 editorial written by a prominent member of the urological community. These are 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.

Prostate cancer mortality rates in Peru and its geographical regions

Junior Smith Torres-Roman*†, Eloy F. Ruiz‡, Jose Fabian Martinez-Herrera§, Sonia Faria Mendes Braga, Luis Taxa**, Jorge Saldaña-Gallo*, Mariela R. Pow-Sang††, Julio M. Pow-Sang‡‡ and Carlo La Vecchia§§

 

*Clinica de Urologia Avanzada UROZEN, Lima, †Facultad de Medicina Humana, Universidad Nacional San Luis Gonzaga, Ica, ‡CONEVID, Unidad de Conocimiento y Evidencia, Universidad Peruana Cayetano Heredia, Lima, Peru, §Cancer Center, Medical Center American British Cowdray, Mexico City, Mexico, Department of Social and Preventive Medicine, Faculty of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil, **Instituto Nacional de Enfermedades Neoplásicas, ††Department of Urology, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru, ‡‡Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL, USA, and §§Department of Clinical Sciences and Community Health, Universitá degli Studi di Milano, Milan, Italy

 

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Abstract

Objective

To evaluate the mortality rates for prostate cancer according to geographical areas in Peru between 2005 and 2014.

Materials and Methods

Information was extracted from the Deceased Registry of the Peruvian Ministry of Health. We analysed age‐standardised mortality rates (world population) per 100 000 men. Spatial autocorrelation was determined according to the Moran Index. In addition, we used Cluster Map to explore relations between regions.

Fig. 1. Peru geographical zones by provinces. The asterisk denotes the province of Callao. Source: National Statistics Institute

Results

Mortality rates increased from 20.9 (2005–2009) to 24.1 (2010–2014) per 100 000 men, an increase of 15.2%. According to regions, during the period 2010–2014, the coast had the highest mortality rate (28.9 per 100 000), whilst the rainforest had the lowest (7.43 per 100 000). In addition, there was an increase in mortality in the coast and a decline in the rainforest over the period 2005–2014. The provinces with the highest mortality were Piura, Lambayeque, La Libertad, Callao, Lima, Ica, and Arequipa. Moreover, these provinces (except Arequipa) showed increasing trends during the years under study. The provinces with the lowest observed prostate cancer mortality rates were Loreto, Ucayali, and Madre de Dios. This study showed positive spatial autocorrelation (Moran’s I: 0.30, P= 0.01).

Conclusion

Mortality rates from prostate cancer in Peru continue to increase. These rates are higher in the coastal region compared to those in the highlands or rainforest.

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Editorial: The burden of urological cancers in low‐ and middle‐income countries

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The burden of cancer in low‐ and middle‐income countries (LMICs) continues to rise [1]. Evaluation of geographical differences in cancer mortality statistics is specifically of interest in LMICs as (inter)national guidelines are potentially less embedded in standard care, and objective measurements to assess underlying mechanisms/explanations for the burden of cancer are often lacking. Monitoring mortality statistics in these countries can thus help assess the effectiveness of national and regional health systems in treating and caring for patients with cancer [1].

Torres‐Roman et al. [2] deserve to be congratulated for their efforts to monitor mortality rates for prostate cancer at both a regional and national level in Peru. The CONCORD initiative from the WHO previously reported prostate cancer statistics for Peru, but data were limited to the capital area of Lima [1]. Torres‐Raman et al. [2] report prostate cancer mortality rates between 2005 and 2014 based on data from the Peruvian Ministry of Health, which covers ~70% of all healthcare providers in Peru. Apart from an overall increase of 15% in mortality rates, substantial variation was observed by geographical region. Mortality rates increased by 16% in the coastal region and highlands, whereas in the rainforest region the rates decreased by 19% [2]. One potential explanation for these observed differences could be the difference in ethnic and racial characteristics. The coastal region in Peru has a strong African influence and also has a larger proportion of men aged >65 years. In addition to potential differences in access to healthcare, some of the variation in prostate cancer mortality statistics most likely reflects a deficiency in reporting systems. Even though this study has its limitations due to missing data and lack of information on other important variables, such as ethnicity and socioeconomic status, it provides a first base for a critical assessment of prostate cancer care in Peru.

Studies like this one from Torres‐Roman et al. [2] show that there is a need for improvement and standardisation of (prostate) cancer care in LMICs, but also a need for improvement in data capturing, so that objective measurements can be put in place. The years of healthy life lost due to prostate cancer, as well as other urological cancers, in LMICs is increasing substantially. Even though each tumour group has its own specifications in terms of prevention and control, an epidemiological assessment of cancer burden based on the experience for urological cancers (i.e., prostate, bladder, kidney and testicular) can therefore inform future assessments of cancer burden. The urological tumour group covers both common and less common cancers (e.g. prostate vs kidney cancer), sex‐specific and cancers that affect both sexes (e.g. testicular vs bladder cancer), cancers with less known risk factors and those strongly linked with lifestyle risk factors (e.g. prostate vs bladder cancer).

It is encouraging to see an increase in the number of studies evaluating the burden of cancer in LMICs [3]; however, given the consistency in observations of an increase in mortality, there is an urgent need to further invest in prevention and management, as well as the infrastructure to collect all relevant data at a national level in these LMICs. Accurate information about cancer burden and how this varies between regions is essential to plan for an adequate health‐system response.

References

  1. Allemani, C, Matsuda, T, Carlo, V et al. Global surveillance of trends in cancer survival 2000‐14 (CONCORD‐3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population‐based registries in 71 countries. Lancet 2018; 391: 1023– 75
  2. Torres‐Roman, J, Ruiz, E, Martinez‐Herrera, J et al. Prostate cancer mortality rates in Peru and its geographic regions. BJU Int 2019; 123: 595– 601
  3. Carioli, G, Vecchia, C, Bertuccio, P et al. Cancer mortality predictions for 2017 in Latin America. Ann Oncol 2017; 28: 2286– 97

 

Article of the week: Ultrasound characteristics of regions identified as suspicious by MRI predict the likelihood of clinically significant cancer on MRI–ultrasound fusion‐targeted biopsy

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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 editorial written by a prominent member of the urological community, and a video made by the authors. These are 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.

 

The ultrasound characteristics of regions identified as suspicious by magnetic resonance imaging (MRI) predict the likelihood of clinically significant cancer on MRI–ultrasound fusion‐targeted biopsy

Benjamin Press*, Andrew B. Rosenkrantz†, Richard Huang‡ and Samir S. Taneja§ 
 
*Rutgers New Jersey Medical School, Newark, NJ, †Department of Radiology, ‡Department of Urology, and §Departments of Urology and Radiology, NYU Langone Health, New York, NY, USA
 
Read the full article

Abstract

Objective

To determine whether the presence of an ultrasound hypoechoic region at the site of a region of interest (ROI) on magnetic resonance imaging (MRI) results in improved prostate cancer (PCa) detection and predicts clinically significant PCa on MRI–ultrasonography fusion‐targeted prostate biopsy (MRF‐TB).

Materials and Methods

Between July 2011 and June 2017, 1058 men who underwent MRF‐TB, with or without systematic biopsy, by a single surgeon were prospectively entered into an institutional review board‐approved database. Each MRI ROI was identified and scored for suspicion by a single radiologist, and was prospectively evaluated for presence of a hypoechoic region at the site by the surgeon and graded as 0, 1 or 2, representing none, a poorly demarcated ROI‐HyR, or a well demarcated ROI‐HyR, respectively. The interaction of MRI suspicion score (mSS) and ultrasonography grade (USG), and the prediction of cancer detection rate by USG, were evaluated through univariate and multivariate analysis.

Results

For 672 men, the overall and Gleason score (GS) ≥7 cancer detection rates were 61.2% and 39.6%, respectively. The cancer detection rates for USGs 0, 1 and 2 were 46.2%, 58.6% and 76.0% (P < 0.001) for any cancer, and 18.7%, 35.2% and 61.1% (P < 0.001) for GS ≥7 cancer, respectively. For MRF‐TB only, the GS ≥7 cancer detection rates for USG 0, 1 and 2 were 12.8%, 25.7% and 52.0%, respectively (P < 0.001). On univariate analysis, in men with mSS 2–4, USG was predictive of GS ≥7 cancer detection rate. Multivariable regression analysis showed that USG, prostate‐specific antigen density and mSS were predictive of GS ≥7 PCa on MRF‐TB.

Conclusions

Ultrasonography findings at the site of an MRI ROI independently predict the likelihood of GS ≥7 PCa, as men with a well‐demarcated ROI‐HyR at the time of MRF‐TB have a higher risk than men without.
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Editorial: Is transrectal ultrasonography of the prostate obsolete in the MRI era?

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Sampling of prostate tissue to confirm pathologically a clinical suspicion of cancer has undergone an exponential change. The random systematic prostate biopsy technique was the only method used for many decades, initially guided by the finger but, since 1989, performed with TRUS guidance. Now, within the space of only a few years, we have entered the era of performing prostate biopsies on the basis of high‐tech three‐dimensional multiparametric MRI images, including software that can track the exact course of the biopsy needle [1]. While new technical developments in general lead to better, more individually directed healthcare, there is always the risk of abandoning ‘old’ but well developed and extensively tested techniques too soon. In this issue of the BJUI, Press et al. [2] looked at the added value of the presence of an ‘old‐fashioned’ TRUS‐detected lesion in cancer‐suspicious regions on MRI to better predict the presence of clinically significant prostate cancer (csPCa) defined as Gleason score ≥7. In their study comprising 1058 men, it was shown that a well‐demarcated abnormal TRUS finding noted at the time of MRI‐TRUS fusion‐guided prostate biopsy coincides with an increased risk of csPCa detection, independent of MRI suspicion (Prostate Imaging Reporting and Data System [PI‐RADS] score).

Increasing PI‐RADS score is correlated with an increased percentage of csPCa after targeted biopsy, both at initial and repeat biopsy. In a review based on data from 8252 men, it was shown that there is a gradual increase in the detection of csPCa from PI‐RADS 3 to PI‐RADS 4 to PI‐RADS 5 index lesions. For example, at first biopsy, the overall rate of PCa detection and the percentage of csPCa were 39%, 62% and 92% and 54%, 63% and 76% for PI‐RADS 3, 4 and 5 lesions, respectively. This means that in men with PI‐RADS 3 lesions, representing approximately one‐third of men deemed eligible for further assessment, only 39% will be diagnosed with PCa and half of the PCa detected will be potentially indolent Gleason 6 PCa [3]. This makes this group of men extremely interesting for further risk stratification before biopsy. Multivariable risk stratification in which PSA density plays an important role has been shown to be of value in these men [4] but further refinement could potentially be made by including suspicious lesions identified at TRUS.

Apart from the added value of TRUS findings in terms of risk stratification, the performance of the MRI‐targeted biopsy itself could be improved by visual guidance of hypoechoic lesions. In the present study by Press et al [2], a hypoechoic TRUS lesion was present at or near the location of two‐thirds of cancer‐suspicious lesions on MRI. The authors more or less advise to direct the targeted biopsy cores not only to the MRI suspicious lesion, but also the TRUS suspicious lesion, both of which often do not fully overlay in a software‐assisted MRI‐TRUS fusion model. The extent to which this ‘correction for misregistration’ is already included during targeted biopsy in current clinical practice is unknown. Although feasible and seemingly important during software‐assisted fusion targeted biopsy, TRUS lesions in cancer‐suspicious MRI regions might be more frequently targeted during cognitive fusion‐targeted biopsy. Two recent studies underline the important message of the present study, and show that a considerable proportion of csPCa is missed in and around MRI‐suspicious lesions by targeted biopsies, as a result of sampling errors related to both misregistration and intra‐tumour heterogeneity [5, 6]. As suggested by these studies, visual guidance by hypoechoic lesions and ‘focal saturation’ biopsy by additional (peri‐)lesional cores might improve the detection of csPCa.

In summary, ‘good old’ TRUS could be of value in those patients who are virtually always present in scenarios in which a grading system is being used, i.e. patients belonging to the so‐called grey zone. The challenge of risk stratification (i.e. personalized medicine) is to nibble at both sides of the grey zone by implementing new techniques or, more likely by implementing a combination of all available and relevant knowledge.

by Monique J. Roobol, Frank-Jan H. Drost and Arnout R. Alberts

References

  1. Verma, S, Choyke, PL, Eberhardt, SC et al. The current state of MR imaging‐targeted biopsy techniques for detection of prostate cancer. Radiology 2017; 285: 343–56
  2. Press, B, Rosenkrantz, AB, Huang, R, Taneja, SS. The ultrasound characteristics of MRI suspicious regions predict the likelihood of clinically significant cancer on MRI‐ultrasound fusion targeted biopsy. BJUI 2019; 123: 439–46.
  3. Schoots, IG. MRI in early prostate cancer detection: how to manage indeterminate or equivocal PI‐RADS 3 lesions? Transl Androl Urol 2018; 7: 70–82
  4. Alberts, AR, Schoots, IG, Bokhorst, LP, Leenders, GJ, Bangma, CH, Roobol, MJ. Risk‐based patient selection for magnetic resonance imaging‐targeted prostate biopsy after negative transrectal ultrasound‐guided random biopsy avoids unnecessary magnetic resonance imaging scans. Eur Urol 2016; 69: 1129–34
  5. Simmons, LAM, Kanthabalan, A, Arya, M et al. Accuracy of transperineal targeted prostate biopsies, visual estimation and image fusion in men needing repeat biopsy in the PICTURE trial. J Urol 2018; 200: 1227–34
  6. Leest, M, Cornel, E, Israel, B et al. Head‐to‐head comparison of transrectal ultrasound‐guided prostate biopsy versus multiparametric prostate resonance imaging with subsequent magnetic resonance‐guided biopsy in biopsy‐naive men with elevated prostate‐specific antigen: a large prospective multicenter clinical study. Eur Urol 2018; [Epub ahead of print]. https://doi.org/10.1016/j.eururo.2018.11.023.

 

Video: Ultrasound characteristics of MRI suspicious regions predict the likelihood of clinically significant cancer on MRI-ultrasound fusion-targeted biopsy

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The ultrasound characteristics of regions identified as suspicious by magnetic resonance imaging (MRI) predict the likelihood of clinically significant cancer on MRI–ultrasound fusion‐targeted biopsy

 
 

Abstract

Objective

To determine whether the presence of an ultrasound hypoechoic region at the site of a region of interest (ROI) on magnetic resonance imaging (MRI) results in improved prostate cancer (PCa) detection and predicts clinically significant PCa on MRI–ultrasonography fusion‐targeted prostate biopsy (MRF‐TB).

Materials and Methods

Between July 2011 and June 2017, 1058 men who underwent MRF‐TB, with or without systematic biopsy, by a single surgeon were prospectively entered into an institutional review board‐approved database. Each MRI ROI was identified and scored for suspicion by a single radiologist, and was prospectively evaluated for presence of a hypoechoic region at the site by the surgeon and graded as 0, 1 or 2, representing none, a poorly demarcated ROI‐HyR, or a well demarcated ROI‐HyR, respectively. The interaction of MRI suspicion score (mSS) and ultrasonography grade (USG), and the prediction of cancer detection rate by USG, were evaluated through univariate and multivariate analysis.

Results

For 672 men, the overall and Gleason score (GS) ≥7 cancer detection rates were 61.2% and 39.6%, respectively. The cancer detection rates for USGs 0, 1 and 2 were 46.2%, 58.6% and 76.0% (P < 0.001) for any cancer, and 18.7%, 35.2% and 61.1% (P < 0.001) for GS ≥7 cancer, respectively. For MRF‐TB only, the GS ≥7 cancer detection rates for USG 0, 1 and 2 were 12.8%, 25.7% and 52.0%, respectively (P < 0.001). On univariate analysis, in men with mSS 2–4, USG was predictive of GS ≥7 cancer detection rate. Multivariable regression analysis showed that USG, prostate‐specific antigen density and mSS were predictive of GS ≥7 PCa on MRF‐TB.

Conclusions

Ultrasonography findings at the site of an MRI ROI independently predict the likelihood of GS ≥7 PCa, as men with a well‐demarcated ROI‐HyR at the time of MRF‐TB have a higher risk than men without.
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Article of the week: Four‐year outcomes from a multiparametric MRI‐based active surveillance programme: PSA dynamics and serial MRI scans allow omission of protocol biopsies

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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 editorial written by a prominent member of the urological community, and a video made by the authors. These are 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.

 

Four‐year outcomes from a multiparametric magnetic resonance imaging (MRI)‐based active surveillance programme: PSA dynamics and serial MRI scans allow omission of protocol biopsies

Kevin Michael Gallagher*, Edward Christopher*†, Andrew James Cameron*, Scott Little*, Alasdair Innes*, Gill Davis*, Julian Keanie‡, Prasad Bollina* and
Alan McNeill*
 
*Department of Urology, Western General Hospital, †College of Medicine and Veterinary Medicine, University of Edinburgh, and ‡Department of Radiology, Western General Hospital, Edinburgh, UK
 
 
Read the full article

Abstract

Objectives

To report outcomes from a multiparametric (mp) magnetic resonance imaging (MRI)‐based active surveillance programme that did not include performing protocol biopsies after the first confirmatory biopsy.

Patients and Methods

All patients diagnosed with Gleason 3 + 3 prostate cancer because of a raised PSA level who underwent mpMRI after diagnosis were included. Patients were recorded in a prospective clinical database and followed up with PSA monitoring and repeat MRI. In patients who remained on active surveillance after the first MRI (with or without confirmatory biopsy), we investigated PSA dynamics for association with subsequent progression. Comparison between first and second MRI scans was undertaken. Outcomes assessed were: progression to radical therapy at first MRI/confirmatory biopsy and progression to radical therapy in those who remained on active surveillance after first MRI.

Results

A total of 211 patients were included, with a median of 4.2 years of follow‐up. The rate of progression to radical therapy was significantly greater at all stages among patients with visible lesions than in those with initially negative MRI (47/125 (37.6%) vs 11/86 (12.8%); odds ratio 4.1 (95% CI 2.0–8.5), P < 0.001). Only 1/56 patients (1.8%) with negative initial MRI scans who underwent a confirmatory systematic biopsy had upgrading to Gleason 3 + 4 disease. PSA velocity was significantly associated with subsequent progression in patients with negative initial MRI (area under the curve 0.85 [95% CI 0.75–0.94]; P <0.001). Patients with high‐risk visible lesions on first MRI who remained on active surveillance had a high risk of subsequent progression 19/76 (25.0%) vs 9/84 (10.7%) for patients with no visible lesions, despite reassuring targeted and systematic confirmatory biopsies and regardless of PSA dynamics.

Conclusion

Men with low‐risk Gleason 3 + 3 prostate cancer on active surveillance can forgo protocol biopsies in favour of MRI and PSA monitoring with selective re‐biopsy.

Read more Articles of the week

Editorial: Re‐thinking active surveillance for the multiparametric magnetic resonance imaging era

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The last decade has seen a dramatic change in the management of low‐risk prostate cancer. Active surveillance (AS) has moved from a controversial management strategy to the preferred option for men with low‐risk disease. Despite widespread acceptance, there remain aspects of the pathway that men find difficult to accept, including the need for numerous repeat surveillance biopsies. In this issue of the BJUI, Gallagher et al. [1] report the outcomes of an AS programme using selective repeat biopsy based on multiparametric MRI (mpMRI) and PSA dynamics. The authors address the important issue of whether mpMRI can be used to safely avoid repeat biopsies in AS protocols.

The evidence for repeat biopsies in AS is based on studies from the pre‐MRI era, where up to 30% of men were upgraded on repeat systematic TRUS biopsy [2]. It has been established that TRUS biopsy is a highly unreliable test and misses a substantial proportion of clinically significant disease. The current approach requiring the repeated application of an unreliable test will not improve the systematic error inherent to the test. It is clear that the pathway needs to be updated for the mpMRI era, and the cohort of men in Gallagher et al. [1] provides valuable real‐life clinical data of an mpMRI‐based AS programme with a unique 4‐year follow‐up period.

The results are encouraging, with upgrading occurring in only 1.8% of men with a prior negative MRI. With follow‐up, progression to radical treatment was 12.8%, which is consistent with the established diagnostic performance of mpMRI. The authors seek further improvements by investigating if PSA dynamics can identify men with a negative MRI at risk of progression. They find that PSA velocity is strongly associated with subsequent progression (AUC 0.95, P < 0.001) and conclude that men on AS with low‐risk disease can safely avoid biopsy in favour of MRI, PSA monitoring and selective re‐biopsy. This study [1] supports a growing body of evidence that mpMRI may be adopted as the primary surveillance tool for men on AS. The finding regarding PSA velocity should be interpreted carefully as it contrasts with previous studies, which found that PSA dynamics have a limited role as independent predictors of disease progressions in AS [3]. A non‐invasive alternative to biopsy would be a valuable addition to AS and improve its acceptability as a management option. The burden of repeat surveillance biopsies for men on AS should not be underestimated. Indeed, in the present study ~30% of men declined biopsy in favour of continued mpMRI surveillance. The question is can we adapt our current standard AS approach for the mpMRI era? There are still many challenges and many unanswered questions. The cost‐effectiveness of mpMRI surveillance programmes needs to be established and the lack of MRI capacity remains a significant obstacle in introducing mpMRI pathways. The optimal imaging interval and the natural history of mpMRI lesions are just a few of the questions that need further research. These are exciting times to be a researcher in this field and there is much work to do as we start to build the new evidence‐base covering all the questions required for the mpMRI era.

References

  1. Gallagher KM, Christopher E, Cameron AJ et al. Four‐year outcomes from a multiparametric magnetic resonance imaging (MRI)‐based active surveillance programme: PSA dynamics and serial MRI scans allow omission of protocol biopsies. BJU Int 2019; 123: 429–38.
  2. Dall’Era MA, Albertsen PC, Bangma C et al. Active surveillance for prostate cancer: a systematic review of the literature. Eur Urol 2012; 62:976–83
  3. Loblaw A, Zhang L, Lam A et al. Comparing prostate specific antigen triggers for intervention in men with stable prostate cancer on active surveillance. J Urol 2010; 184: 1942–6

 

Video: Four-year outcomes from a multiparametric MRI based active surveillance programme

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Four‐year outcomes from a multiparametric magnetic resonance imaging (MRI)‐based active surveillance programme: PSA dynamics and serial MRI scans allow omission of protocol biopsies

 

Abstract

Objectives

To report outcomes from a multiparametric (mp) magnetic resonance imaging (MRI)‐based active surveillance programme that did not include performing protocol biopsies after the first confirmatory biopsy.

Patients and Methods

All patients diagnosed with Gleason 3 + 3 prostate cancer because of a raised PSA level who underwent mpMRI after diagnosis were included. Patients were recorded in a prospective clinical database and followed up with PSA monitoring and repeat MRI. In patients who remained on active surveillance after the first MRI (with or without confirmatory biopsy), we investigated PSA dynamics for association with subsequent progression. Comparison between first and second MRI scans was undertaken. Outcomes assessed were: progression to radical therapy at first MRI/confirmatory biopsy and progression to radical therapy in those who remained on active surveillance after first MRI.

Results

A total of 211 patients were included, with a median of 4.2 years of follow‐up. The rate of progression to radical therapy was significantly greater at all stages among patients with visible lesions than in those with initially negative MRI (47/125 (37.6%) vs 11/86 (12.8%); odds ratio 4.1 (95% CI 2.0–8.5), P < 0.001). Only 1/56 patients (1.8%) with negative initial MRI scans who underwent a confirmatory systematic biopsy had upgrading to Gleason 3 + 4 disease. PSA velocity was significantly associated with subsequent progression in patients with negative initial MRI (area under the curve 0.85 [95% CI 0.75–0.94]; P <0.001). Patients with high‐risk visible lesions on first MRI who remained on active surveillance had a high risk of subsequent progression 19/76 (25.0%) vs 9/84 (10.7%) for patients with no visible lesions, despite reassuring targeted and systematic confirmatory biopsies and regardless of PSA dynamics.

Conclusion

Men with low‐risk Gleason 3 + 3 prostate cancer on active surveillance can forgo protocol biopsies in favour of MRI and PSA monitoring with selective re‐biopsy.

 

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Article of the month: Mortality after radical prostatectomy in a matched contemporary cohort in Sweden compared to the Scandinavian Prostate Cancer Group 4 study

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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 editorial written by a prominent member of the urological community. These are 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.

 

Mortality after radical prostatectomy in a matched contemporary cohort in Sweden compared to the Scandinavian Prostate Cancer Group 4 (SPCG‐4) study

Walter Cazzaniga*†‡, Hans Garmo§¶, David Robinson**, Lars Holmberg‡, Anna Bill-Axelson‡ and Pär Stattin‡
 
 
*Division of Experimental Oncology/Unit of Urology URI, IRCCS Ospedale San Raffaele, †University Vita-Salute San Raffaele, Milan, Italy, ‡Department of Surgical Sciences, Uppsala University, §Regional Cancer Centre Uppsala Örebro, Uppsala University Hospital, Uppsala, Sweden, Division of Cancer Studies, Cancer Epidemiology Group, King’s College London, London, UK, and **Department of Urology, Ryhov Hospital, Jönköping, Sweden
 

 

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Abstract

Objectives

To investigate if results in terms of absolute risk in mature randomised trials are relevant for contemporary decision‐making. To do so, we compared the outcome for men in the radical prostatectomy (RP) arm of the Scandinavian Prostate Cancer Group Study number 4 (SPCG‐4) randomised trial with matched men treated in a contemporary era before and after compensation for the grade migration and grade inflation that have occurred since the 1980s.

Patients and Methods

A propensity score‐matched analysis of prostate cancer mortality and all‐cause mortality in the SPCG‐4 and matched men in the National Prostate Cancer Register (NPCR) of Sweden treated in 1998–2006 was conducted. Cumulative incidence of prostate cancer mortality and all‐cause mortality was calculated. Cox proportional hazards regression analyses were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for a matching on original Gleason Grade Groups (GGG) and second, matching with GGG increased one unit for men in the NPCR.

 
Figure 1: Cumulative incidence of prostate cancer mortality (PCM) and all‐cause mortality (ACM) in the SPCG‐4 and the NPCR of Sweden. FU, follow‐up after date of diagnosis or primary treatment. A and B based on original GGG. C and D based on upgraded GGG classification in the NPCR with an increase of one grade in GGG.

Results

Matched men in the NPCR treated in 2005–2006 had half the risk of prostate cancer mortality compared to men in the SPCG‐4 (HR 0.46, 95% CI 0.19–1.14). In analysis of men matched on an upgraded GGG in the NPCR, this difference was mitigated (HR 0.73, 95% CI 0.36–1.47).

Conclusion

Outcomes after RP for men in the SPCG‐4 cannot be directly applied to men in the current era, mainly due to grade inflation and grade migration. However, by compensating for changes in grading, similar outcomes after RP were seen in the SPCG‐4 and NPCR. In order to compare historical trials with current treatments, data on temporal changes in detection, diagnostics, and treatment have to be accounted for.

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