Tag Archive for: #ProstateCancer

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Article of the week: ‘Dr Google’: trends in online interest in prostate cancer screening, diagnosis and treatment

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 and a visual abstract written by prominent members 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 month, it should be this one.

‘Dr Google’: trends in online interest in prostate cancer screening, diagnosis and treatment

Michael E. Rezaee*, Briana Goddard, Einar F. Sverrisson*, John D. Seigne* and Lawrence M. Dagrosa*

*Section of Urology, Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, and Geisel School of Medicine, Hanover

Abstract

Objectives

To examine trends in online search behaviours related to prostate cancer on a national and regional scale using a dominant major search engine.

Materials and Methods

Google Trends was queried using the terms ‘prostate cancer’, ‘prostate‐specific antigen’ (PSA), and ‘prostate biopsy’ between January 2004 and January 2019. Search volume index (SVI), a measure of relative search volume on Google, was obtained for all terms and examined by region and time period: pre‐US Preventive Services Task Force (USPSTF) Grade D draft recommendation on PSA screening; during the active Grade D recommendation; and after publication of the recent Grade C draft recommendation.

Results

Online interest in PSA screening differed by time period (P < 0.01). The SVI for PSA screening was greater pre‐Grade D draft recommendation (82.7) compared to during the recommendation (74.5), while the SVI for PSA screening was higher post‐Grade C draft recommendation (90.4) compared to both prior time periods. Similar results were observed for prostate biopsy and prostate cancer searches. At the US state level, online interest in prostate cancer was highest in South Carolina (SVI 100) and lowest in Hawaii (SVI 64). For prostate cancer treatment options, online interest in cryotherapy, prostatectomy and prostate cancer surgery overall increased, while searches for active surveillance, external beam radiation, brachytherapy and high‐intensity focused ultrasonography remained stable.

Conclusion

Online interest in prostate cancer has changed over time, particularly in accordance with USPSTF screening guidelines. Google Trends may be a useful tool in tracking public interest in prostate cancer screening, diagnosis and treatment, especially as it relates to major shifts in practice guidelines.

Editorial: Does Dr Google give good advice about prostate cancer?

In this issue of BJUI, Rezaee et al. [1] report on Google trends as a barometer of public interest in PSA screening and different types of prostate cancer treatment in the USA. Not surprisingly, they found a decrease in Google searches about PSA screening after the US Preventive Services Task Force (USPSTF) issued a Grade D recommendation against screening. This corresponds with observed trends of decreased PSA screening in the population [2]. Notably, the volume of Google searches about PSA screening rebounded after the USPSTF changed to a Grade C recommendation for shared decision-making about screening. It is unknown whether this actually reflects a greater number of men discussing PSA screening with their doctors, or whether online information had an impact on their decisions.

Meanwhile, the quantity of Google search activity varied between different types of prostate cancer treatment. In the USA, search volume was higher for surgery than for active surveillance, and there was a greater search volume for high intensity focused ultrasonography (HIFU) than for external beam radiation therapy or brachytherapy. Notably, another recent study examined global Google trends in searches on prostate cancer treatment, showing increasing annual relative search volume for focal therapy and active surveillance over time [3]. The underlying reasons for these temporal and geographic differences in ‘public interest’ may be multifactorial, including recommendations from physicians and professional societies, support from policy-makers, public awareness campaigns from healthcare-related organizations and marketing from commercial companies. Whether the change in ‘public interest’ had any impact on treatment selection remains unknown.

As an increasing number of people are going online for health information, digital platforms provide useful barometers for public interest in different topics. For example, another recent study reported that prostate cancer was a topic with high public interest based on the number of video views on YouTube compared to other urological conditions [4]. While interesting, the number of Google searches or views on YouTube do not provide any insights into who is searching for the information, their motivation, and the quality of information that they received.

Concerningly, several recent studies have called into question the accuracy of information about prostate cancer across multiple online platforms. Asafu-Adjei et al. [5] reported that websites on HIFU and cryotherapy had a substantial amount of incomplete or inaccurate information. Alsyouf et al. [6] reported that seven of the 10 most commonly shared articles about prostate cancer on social media were inaccurate or misleading. Finally, our group reported that 77% of the first 150 YouTube videos about prostate cancer had potentially misinformative and/or biased content in the video itself or the comments underneath [7]. Alarmingly, the quality of information was inversely correlated with the number of views. More research is needed to evaluate the impact of exposure to online misinformation on prostate cancer screening and treatment.

Overall, the online environment holds great promise and also great peril in prostate cancer. On one hand, digital networks have opened up new opportunities for global scientific exchange and have the potential to greatly improve patient care. Conversely, there is a substantial amount of misinformation on the internet, and the potential for a negative impact on patients and their families. As a urological community, we should be pro-active about directing our patients to trustworthy online resources, and should actively participate in digital networks to help share high-quality information with the public. More strategic effort should also be made to maximize the degree of reach and engagement upon dissemination of high-quality information.

by Stacy Loeb, Nataliya Byrne and Jeremy Teoh

References

  1. Rezaee ME, Goddard B, Sverrisson EF, Seigne JD, Dagrosa LM. ‘Dr Google’: trends in online interest in prostate cancer screening, diagnosis and treatment. BJU Int 2019; 124: 629–34
  2. Magnani CJ, Li K, Seto T et al. PSA Testing Use and Prostate Cancer Diagnostic Stage After the 2012 U.S. Preventive Services Task Force Guideline Changes. JNCCN 2019; 17: 795–803
  3. Cacciamani GE, Bassi S, Sebben M et al. Consulting “Dr. Google” for prostate cancer treatment options. A contemporary worldwide trend analysis. Eur Urol Oncol 2019; https://doi.org/10.1016/j.euo.2019.07.002
  4. Borgmann H, Salem J, Baunacke M et al. Mapping the landscape of urology: a new media-based cross-sectional analysis of public versus academic interest. Int J Urol 2018; 25: 421–8
  5. Asafu-Adjei D, Mikkilineni N, Sebesta E, Hyams E. Misinformation on the Internet regarding Ablative Therapies for Prostate Cancer. Urology 2019; https://doi.org/10.1016/j.urology.2018.12.050
  6. Alsyouf M, Stokes P, Hur D, Amasyali A, Ruckle H, Hu B. ‘Fake News’ in urology: evaluating the accuracy of articles shared on social media in genitourinary malignancies. BJU Int 2019; 124: 701–6
  7. Loeb S, Sengupta S, Butaney M et al. Dissemination of Misinformative and Biased Information about Prostate Cancer on YouTube. Eur Urol 2019; 27: 564–7

 

Article of the month: Risk of metastatic disease on 68-gallium‐prostate‐specific membrane antigen PET/CT scan for primary staging of 1253 men at the diagnosis of PCa

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  and a video prepared 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 month, it should be this one.

Risk of metastatic disease on 68Gallium‐prostate‐specific membrane antigen positron emission tomography/computed tomography scan for primary staging of 1253 men at the diagnosis of prostate cancer

John W. Yaxley*†‡, Sheliyan Raveenthiran†‡, François-Xavier Nouhaud‡§, Hemamali Samaratunga†¶, William J. Yaxley†‡, Geoff Coughlin*, Anna J. Yaxley**, Troy Gianduzzo††, Boon Kua‡‡, Louise McEwan‡‡ and David Wong‡‡

 

*Wesley Urology Clinic, Department of Medicine, University of Queensland, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia, §Department of Urology, Rouen University Hospital, Rouen, France, Aquesta Uro-pathology, **School of Medicine, Griffith University, ††Brisbane Prostate Clinic, and ‡‡Wesley Medical Imaging, Brisbane, Queensland, Australia

Abstract

Objective

To determine the number of men with 68gallium‐prostate‐specific membrane antigen positron emission tomography/computed tomography (68Ga‐PSMA PET/CT) avid metastasis at diagnosis, as most data on 68Ga‐PSMA PET/CT are for the evaluation of recurrent disease after primary treatment and to our knowledge this study is the largest series of primary prostate cancer staging with 68Ga‐PSMA PET/CT.

Patients and Methods

A retrospective review conducted on 1253 consecutive men referred by urologists or radiation oncologists to our tertiary referral centre for 68Ga‐PSMA PET/CT scan for staging at the initial diagnosis of prostate cancer between July 2014 and June 2018.

The primary outcome measure was to determine the risk of metastasis based on 68Ga‐PSMA PET/CT. Patients were risk stratified based on histological biopsy International Society of Urological Pathology (ISUP) grade, prostate‐specific antigen (PSA) level, and staging with pre‐biopsy multiparametric magnetic resonance imaging (mpMRI). Univariate and multivariate logistic regression were used to analyse results.

Results

The median PSA level was 6.5 ng/mL and median ISUP grade was 3, with high‐risk disease in 49.7%. The prostate primary was PSMA avid in 91.7% of men. Metastatic disease was identified in 12.1% of men, including 8.2% with a PSA level of <10 ng/mL and 43% with a PSA level of >20 ng/mL. Metastases were identified in 6.4% with ISUP grade 2–3 and 21% with ISUP grade 4–5. Pre‐biopsy mpMRI identified metastasis in 8.1% of T2 disease, increasing to 42.4% of T3b. Lymph node metastases were suspected in 107 men, with 47.7% outside the boundaries of an extended pelvic lymph node dissection. Skeletal metastases were identified in 4.7%. In men with intermediate‐risk prostate cancer, metastases were identified in 5.2%, compared to 19.9% with high‐risk disease.

Conclusions

These results support the use of 68Ga‐PSMA PET/CT for primary staging of prostate cancer. Increasing PSA level, ISUP grade and radiological staging with mpMRI were all statistically significant prognostic factors for metastasis on both univariate and multivariate analysis.

Editorial: PSMA PET/CT imaging for primary staging of intermediate and high-risk PCa

In this month’s issue Yaxley et al. [1] describe a retrospective study of 68Ga-labelled prostate specific membrane antigen (68Ga-PSMA) positron emission tomography – computed tomography (PET/CT) in 1253 men at primary staging. The primary aim was to determine the risk of metastatic disease on 68Ga-PSMA PET/CT in risk categories including prostate specific antigen (PSA) level, ISUP grade and multiparametric magnetic resonance imaging (mpMRI) stage. The majority of patients had PSA < 10 ng/ml (78%) and / or T2 tumours (74%) with a relatively even distribution across ISUP grades from 1 to 5. Overall, metastases were detected in 12.1% of men and unsurprisingly, were more common in patients with high PSA >20ng/ml and/or ISUP 4-5 and/or T3b stage. Increasing PSA, ISUP grade and T-stage were all statistically significant prognostic factors on univariate and multivariate analysis. In men with at least one intermediate risk factor (T2, PSA 10-20 ng/ml, ISUP 2-3), 5.2% had metastases and in those with at least one high risk factor, 19.9% had PSMA-avid metastases.

On a sub-analysis of lymph node metastases (107 men), there was increased risk of nodal disease with increasing PSA, ISUP grade and T-stage. Of note, nearly 50% of lymph node metastases were outside an extended lymph node dissection field. Skeletal metastases, occurring in 59 men, were also more frequent in these higher risk groups. Interestingly, not all primary tumours (91.7%) were PSMA-avid (SUVmax > 3.0), consistent with previous estimations of less than 10% of prostate cancer not expressing PSMA significantly.

There is a large body of evidence supporting the use of 68Ga-PSMA PET/CT in biochemical recurrence of prostate cancer, with superior sensitivity over other PET tracers such as 18F-choline or 18F-fluciclovine, particularly at low PSA levels (1 and 2ng/ml, respectively) [2,3]. There is less evidence supporting the use of 68Ga-PSMA PET/CT in primary staging, although the literature that does exist is positive. In 130 patients with intermediate or high-risk disease, sensitivity and specificity for lymph node detection on a template-based analysis has been reported to be 68.3% and 99.1%, respectively, significantly better sensitivity than conventional morphological imaging (27.3% and 97.1%, respectively) [4]. Whilst, the negative predictive value might not be sufficiently high to avoid considering lymph node dissection in patients at increased risk of nodal metastases, there is nevertheless potential to substantially improve on conventional morphological imaging for nodal staging. In addition, there is evidence that 68Ga-PSMA PET/CT leads to changes in management in at least 21% of patients being staged with intermediate or high-risk disease [5]. The large retrospective cohort reported by Yaxley et al. [1] contributes to this growing evidence base and suggests that 68Ga-PSMA PET/CT has a place in staging high-risk, and probably intermediate risk, patients before definitive treatment. The retrospective nature allows potential referral bias but the data benefits from a large cohort in real-life current practice.

What this study does not tell us is the incremental benefit of 68Ga-PSMA PET/CT over conventional imaging with mpMRI, bone scan and CT scan. However, the prospectively recruiting proPSMA study will provide these data shortly [6]. Secondly, no histopathological or follow up reference standard was available in this study. However, 68Ga-PSMA PET/CT is known to be very specific with few false positive results and the authors adopted a relatively robust criterion for positivity (moderate or high uptake with a CT correlate) to minimise false positive results. However, some sensitivity may have been lost, e.g. mildly positive metastases or PSMA-positive but CT-negative bone lesions, a not infrequent occurrence in our experience. An additional practical detail is that contrast-enhanced CT was employed to aid differentiation of ureteric activity from abdominal and pelvic lymph nodes. This is not routine in all PET departments.

The results from the proPSMA study are eagerly awaited [6]. In the meantime, the imaging and clinical prostate community will also need to tackle the issues of having several 68Ga and 18F-labelled PSMA analogues available to choose from, with subtle differences in biodistribution, diagnostic accuracy and cost. There seems no doubt however, that PSMA-based PET imaging will continue to play a substantial part in the management of patients with prostate cancer at various points in their management pathway and that robust prospective evidence will continue to accumulate to a level that funders will not be able to ignore.

References

  1. Yaxley J, Raveenthiran S, Nouhaud FX, et al. Risk of metastatic disease on 68Ga-PSMA PET/CT scan for primary staging of 1253 men at the diagnosis of prostate cancer. BJU Int 2019; xx: xxx-xxx.
  2. Treglia G, Pereira Mestre R, Ferrari M, et al. Radiolabelled choline versus PSMA PET/CT in prostate cancer restaging: a meta-analysis. Am J Nucl Med Mol Imaging 2019; 9: 127-39.
  3. Calais J, Ceci F, Nguyen K, et al. Prospective head-to-head comparison of 18F-fluciclovine and 68Ga-PSMA-11 PET/CT for localization of prostate cancer biochemical recurrence after primary prostatectomy. J Clin Oncol 2019; 37: 7_suppl, 15-15.
  4. Maurer T, Gschwend JE, Rauscher I, et al. Diagnostic efficacy of (68)Gallium-PSMA positron emission tomography compared to conventional imaging for lymph node staging of 130 consecutive patients with intermediate to high risk prostate cancer. J Urol 2016; 195: 1436-43.
  5. Roach PJ, Francis R, Emmett L, et al. The Impact of (68)Ga-PSMA PET/CT on Management Intent in Prostate Cancer: Results of an Australian Prospective Multicenter Study. J Nucl Med 2018; 59: 82-8.
  6. Hofman MS, Murphy DG, Williams SG, et al. A prospective randomized multicentre study of the impact of gallium-68 prostate-specific membrane antigen (PSMA) PET/CT imaging for staging high-risk prostate cancer prior to curative-intent surgery or radiotherapy (proPSMA study): clinical trial protocol. BJU Int 2018; 122: 783-3.

 

Video: Risk of metastatic disease on 68-Ga‐PSMA PET/CT scan for primary staging of 1253 men with PCa

 

Risk of metastatic disease on 68Gallium‐prostate‐specific membrane antigen positron emission tomography/computed tomography scan for primary staging of 1253 men at the diagnosis of prostate cancer

Abstract

Objective

To determine the number of men with 68gallium‐prostate‐specific membrane antigen positron emission tomography/computed tomography (68Ga‐PSMA PET/CT) avid metastasis at diagnosis, as most data on 68Ga‐PSMA PET/CT are for the evaluation of recurrent disease after primary treatment and to our knowledge this study is the largest series of primary prostate cancer staging with 68Ga‐PSMA PET/CT.

Patients and Methods

A retrospective review conducted on 1253 consecutive men referred by urologists or radiation oncologists to our tertiary referral centre for 68Ga‐PSMA PET/CT scan for staging at the initial diagnosis of prostate cancer between July 2014 and June 2018.

The primary outcome measure was to determine the risk of metastasis based on 68Ga‐PSMA PET/CT. Patients were risk stratified based on histological biopsy International Society of Urological Pathology (ISUP) grade, prostate‐specific antigen (PSA) level, and staging with pre‐biopsy multiparametric magnetic resonance imaging (mpMRI). Univariate and multivariate logistic regression were used to analyse results.

Results

The median PSA level was 6.5 ng/mL and median ISUP grade was 3, with high‐risk disease in 49.7%. The prostate primary was PSMA avid in 91.7% of men. Metastatic disease was identified in 12.1% of men, including 8.2% with a PSA level of <10 ng/mL and 43% with a PSA level of >20 ng/mL. Metastases were identified in 6.4% with ISUP grade 2–3 and 21% with ISUP grade 4–5. Pre‐biopsy mpMRI identified metastasis in 8.1% of T2 disease, increasing to 42.4% of T3b. Lymph node metastases were suspected in 107 men, with 47.7% outside the boundaries of an extended pelvic lymph node dissection. Skeletal metastases were identified in 4.7%. In men with intermediate‐risk prostate cancer, metastases were identified in 5.2%, compared to 19.9% with high‐risk disease.

Conclusions

These results support the use of 68Ga‐PSMA PET/CT for primary staging of prostate cancer. Increasing PSA level, ISUP grade and radiological staging with mpMRI were all statistically significant prognostic factors for metastasis on both univariate and multivariate analysis.

Article of the week: Biparametric vs multiparametric prostate MRI for the detection of PCa in treatment‐naïve patients

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 produced 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.

Biparametric vs multiparametric prostate magnetic resonance imaging for the detection of prostate cancer in treatment-naïve patients: a diagnostic test accuracy systematic review and meta-analysis

Mostafa Alabousi*, Jean-Paul Salameh†‡, Kaela Gusenbauer§, Lucy Samoilov, Ali Jafri**, Hang Yu§ and Abdullah Alabousi††

 

*Department of Radiology, McMaster University, Hamilton, Department of Clinical Epidemiology and Public Health, University of Ottawa, The Ottawa Hospital Research Institute, Clinical Epidemiology Program, Ottawa, §Department of Medicine, McMaster University, Hamilton, Department of Medicine, Western University, London, ON, Canada, **Department of Medicine, New York Institute of Technology School of Osteopathic Medicine, Glen Head, NY, USA, and ††Department of Radiology, St Joseph’s Healthcare, McMaster University, Hamilton, ON, Canada

Abstract

Objective

To perform a diagnostic test accuracy (DTA) systematic review and meta‐analysis comparing multiparametric (diffusion‐weighted imaging [DWI], T2‐weighted imaging [T2WI], and dynamic contrast‐enhanced [DCE] imaging) magnetic resonance imaging (mpMRI) and biparametric (DWI and T2WI) MRI (bpMRI) in detecting prostate cancer in treatment‐naïve patients.

Methods

The Medical Literature Analysis and Retrieval System Online (MEDLINE) and Excerpta Medica dataBASE (EMBASE) were searched to identify relevant studies published after 1 January 2012. Articles underwent title, abstract, and full‐text screening. Inclusion criteria consisted of patients with suspected prostate cancer, bpMRI and/or mpMRI as the index test(s), histopathology as the reference standard, and a DTA outcome measure. Methodological and DTA data were extracted. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)‐2 tool. DTA metrics were pooled using bivariate random‐effects meta‐analysis. Subgroup analysis was conducted to assess for heterogeneity.

Results

From an initial 3502 studies, 31 studies reporting on 9480 patients (4296 with prostate cancer) met the inclusion criteria for the meta‐analysis; 25 studies reported on mpMRI (7000 patients, 2954 with prostate cancer) and 12 studies reported on bpMRI DTA (2716 patients, 1477 with prostate cancer). Pooled summary statistics demonstrated no significant difference for sensitivity (mpMRI: 86%, 95% confidence interval [CI] 81–90; bpMRI: 90%, 95% CI 83–94) or specificity (mpMRI: 73%, 95% CI 64–81; bpMRI: 70%, 95% CI 42–83). The summary receiver operating characteristic curves were comparable for mpMRI (0.87) and bpMRI (0.90).

Conclusions

No significant difference in DTA was found between mpMRI and bpMRI in diagnosing prostate cancer in treatment‐naïve patients. Study heterogeneity warrants cautious interpretation of the results. With replication of our findings in dedicated validation studies, bpMRI may serve as a faster, cheaper, gadolinium‐free alternative to mpMRI.

 

Editorial: Dropping the GAD – just a fad?

It is not without irony that, at the very moment that the UK’s National Institute for Health and Care Excellence (NICE) is poised to ratify the recommendation that multiparametric MRI (mpMRI) be introduced into the prostate cancer diagnostic pathway, we are seeking to significantly modify the very intervention on which they are about to provide judgement on [1].

The modification proposed is both compelling and plausible, as it renders the process of imaging the prostate in order to detect and localise clinically significant prostate cancer; simpler, quicker, safer and cheaper. It entails dropping the most complex and time‐consuming component of the three multiparametric sequences, the dynamic (time‐dependent) T1‐weighted gadolinium‐enhanced (GAD) sequence. This was a sequence that was, in the early days of MRI, imbued to have biological significance because it was capable of exploiting the differences in the microvascular architecture and function that we have tended to associate with cancer and non‐cancer in order to discriminate between the two. Or so we thought [2].

The systematic review in this issue of the BJUI by Alabousi et al. [3] explores, via the process of systematic review, whether the omission of the T1‐GAD sequence results in any clinically important reduction in test performance when compared with the full sequence scan comprising traditionally of T2, diffusion and T1‐GAD sequences. It did not.

By any stretch this is a tough analysis to pull‐off, as T1‐GAD sequences are not standardised in terms of acquisition or reporting. Every group seems to manage the dynamic images in a different way. As such they tend to suffer from quality control issues, possibly to a greater extent than the T2 and diffusion sequences. The verification of the signal by biopsy strategy and sampling intensity will have varied across studies, as will the threshold of the definition of clinically significant prostate cancer. These inherent methodological problems are all familiar to readers and issues that are pertinent to any imaging study in the detection of prostate cancer. However, there are two issues that make any current assessment of GAD vs no GAD really problematic. The first is the almost exclusive reliance on single‐centre retrospective data. In the few studies that claim a prospective design no comparative data were available. Studies of this type are typical in the early phase of exploring a clinical question and will, in time, be corrected. The other, largely hidden, hardly discussed and truly problematic issue relates to the manner by which we synthesise an overall risk score from the MRI sequences that we derive. The near ubiquitous use of the Prostate Imaging‐Reporting and Data System (PI‐RADS) scoring system introduces a systematic bias by the manner in which a Boolean form of logic is used to decide on the degree of influence that each sequence has in relation to the overall score. According to the manner by which PI‐RADS is applied, it tends to render the T1‐GAD sequence subordinate (only relevant in a minority of cases), contingent (to T2/diffusion) and disparate (dependent on prostate zone) in the way it is invoked [4]. The result is, that within the PIRADS framework, the T1‐GAD sequence is destined to play a relatively small role in driving the overall summary score of risk. It might, therefore, not be too surprising if its removal made little difference to the overall detection of clinically significant prostate cancer.

So what are the next steps? Clearly this is a very important issue and a simpler, quicker, safer and cheaper MRI would be desirable from multiple perspectives. It would render what is currently a complex intervention that comprises an invasive component into a totally passive image acquisition in which no medically trained health professional need be present. It is almost certainly a pre‐requisite for adoption in resource-poor jurisdictions and for entertaining the role of MRI as a primary population‐based screening test.

It took a large number of randomised trials to get mpMRI accepted into the prostate cancer diagnostic pathway. What is the minimum amount of evidence required to disinvest in one of its key components? In other words how many clinically significant cancers would we tolerate missing in order to offer the less complex test?

A direct (head‐to‐head) non‐inferiority randomised comparative study would, following some of our own recent calculations, require >3000 men to participate, which might just prove a little too challenging. An alternative approach is a study in which men would have lesions declared using a Likert score, thereby making no prior assumptions on the role and utility of any single sequence, by traditional mpMRI (standard) but also by a T2‐diffusion MRI (experimental) with appropriate blinding. Some lesions would be private to either standard or experimental imaging but most, it is likely, would be shared. All would require sampling. The yield, the misses, the test accuracy for each approach, could be calculated with necessary adjustments for the inevitable incorporation and verification biases.

It is interesting to observe that in many parts of the world mpMRI was introduced by clinicians before a large body of evidence was accumulated because they felt it was the right thing to do [5]. It may well be the case that ‘dropping the GAD’ will be subject to the same decision‐making process and precede any definitive judgement based on reliable evidence. Recent activity on PubMed would suggest that this might already have happened [6].

References

  1. National Institute for Health and Care Excellence (NICE). Non‐invasive MRI scan for Prostate Cancer recommended by NICE. Available at: https://www.nice.org.uk/news/article/non-invasive-mri-scan-for-prostate-cancer-recommended-by-nice. Accessed May 2019.
  2. Little, RABarjat, HHare, JI et al. Evaluation of dynamic contrast‐enhanced MRI biomarkers for stratified cancer medicine: how do permeability and perfusion vary between human tumours? Magn Reson Imaging 20184698– 105
  3. Alabousi, MSalameh, JPGusenbauer, K et al. Biparametric vs multiparametric prostate magnetic resonance imaging for the detection of prostate cancer in treatment‐naïve patients: a diagnostic test accuracy systematic review and meta‐analysis. BJU Int 2019124209– 20
  4. Turkbey, BRosenkrantz, ABHaider, MA et al. Prostate Imaging reporting and Data System version 2.1: 2019 update of Prostate Imaging Reporting and Data System version 2. Eur Urol 2019 [Epub ahead of print]. https://doi.org/10.1016/j.eururo.2019.02.033
  5. Ahmed, HUKirkham, AArya, M et al. Is it time to consider a role for MRI before prostate biopsy? Nat Rev Clin Oncol 20096197– 20
  6. Xu, MFang, MZou, J et al. Using biparametric MRI radiomics signature to differentiate between benign and malignant prostate lesions. Eur J Radiol 201911438– 44

 

Video: Biparametric vs multiparametric prostate MRI for the detection of PCa in treatment‐naïve patients: a diagnostic test accuracy systematic review and meta‐analysis

Abstract

Objective

To perform a diagnostic test accuracy (DTA) systematic review and meta‐analysis comparing multiparametric (diffusion‐weighted imaging [DWI], T2‐weighted imaging [T2WI], and dynamic contrast‐enhanced [DCE] imaging) magnetic resonance imaging (mpMRI) and biparametric (DWI and T2WI) MRI (bpMRI) in detecting prostate cancer in treatment‐naïve patients.

Methods

The Medical Literature Analysis and Retrieval System Online (MEDLINE) and Excerpta Medica dataBASE (EMBASE) were searched to identify relevant studies published after 1 January 2012. Articles underwent title, abstract, and full‐text screening. Inclusion criteria consisted of patients with suspected prostate cancer, bpMRI and/or mpMRI as the index test(s), histopathology as the reference standard, and a DTA outcome measure. Methodological and DTA data were extracted. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)‐2 tool. DTA metrics were pooled using bivariate random‐effects meta‐analysis. Subgroup analysis was conducted to assess for heterogeneity.

Results

From an initial 3502 studies, 31 studies reporting on 9480 patients (4296 with prostate cancer) met the inclusion criteria for the meta‐analysis; 25 studies reported on mpMRI (7000 patients, 2954 with prostate cancer) and 12 studies reported on bpMRI DTA (2716 patients, 1477 with prostate cancer). Pooled summary statistics demonstrated no significant difference for sensitivity (mpMRI: 86%, 95% confidence interval [CI] 81–90; bpMRI: 90%, 95% CI 83–94) or specificity (mpMRI: 73%, 95% CI 64–81; bpMRI: 70%, 95% CI 42–83). The summary receiver operating characteristic curves were comparable for mpMRI (0.87) and bpMRI (0.90).

Conclusions

No significant difference in DTA was found between mpMRI and bpMRI in diagnosing prostate cancer in treatment‐naïve patients. Study heterogeneity warrants cautious interpretation of the results. With replication of our findings in dedicated validation studies, bpMRI may serve as a faster, cheaper, gadolinium‐free alternative to mpMRI.

 

 

 

Article of the week: A transcriptomic signature of tertiary Gleason 5 predicts worse clinicopathological outcome

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 produced 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.

A transcriptomic signature of tertiary Gleason 5 predicts worse clinicopathological outcome

Alberto Martini*, Joanna Wang*, Nicholas M. Brown*, Shivaram Cumarasamy*, John P. Sfakianos*, Ardeshir R. Rastinehad*, Kenneth G. Haines III, Nils Peter Wiklund*, Sujit S. Nair* and Ashutosh K. Tewari*

 

Departments of *Urology and Pathology, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, USA

 

Abstract

Objective

To investigate the genomic features of tertiary pattern 5 (TP5) on radical prostatectomy specimens in an effort to explain the poor clinical outcomes associated with this disease subtype.

Patients and methods

Data from 159 men with Gleason Grade Group (GGG) 3 or 4 were considered. All patients had Decipher diagnostic testing with transcript profiles and single‐channel array normalisation (SCAN)‐normalised expression of coding genes.

The relationship between Decipher and TP5 was investigated by linear and binary logistic regressions. A differential transcriptomic analysis between patients with and without TP5 was performed. The prognostic role of these genes on progression‐free survival (PFS) and overall survival (OS) was evaluated using The Cancer Genome Atlas.

Results

In all, 52/159 (33%) patients had GGG 3–4 with TP5 disease. TP5 was associated with a higher Decipher score (β 0.07, 95% confidence interval [CI] 0.02–0.13; = 0.04) and higher likelihood of falling within the intermediate‐ or high‐risk categories (odds ratio 3.34, 95% CI 1.34–8.35; = 0.01). Analysis of microarray data revealed an 18‐gene signature that was differentially expressed in patients with TP5; 13 genes were over‐ and five under‐expressed in the TP5 cohort.

The overexpression of cyclin dependent kinase inhibitor 2B (CDKN2B), polo‐like kinase 1 (PLK1), or cell division cycle 20 (CDC20) was associated with worse PFS. The group harbouring overexpression of at least one gene had a 5‐year PFS rate of 50% vs 74% in the group without overexpression (P < 0.001).

Conclusions

Our studies have elucidated unique genomic features of TP5, whilst confirming previous clinical findings that patients harbouring TP5 tend to have worse prognosis. This is the first RNA‐based study to investigate the molecular diversity of TP5 and the first correlating CDKN2B to poorer prognosis in patients with prostate cancer.

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