Tag Archive for: Prostate cancer

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Editorial: Reply: RS-RARP vs standard RARP

Since the introduction of robotic surgery in the treatment of patients with prostate cancer (PCa), different surgical innovations have been implemented in order to preserve postoperative functional outcomes while maintaining oncological safety. Sparing the Retzius space during robot‐assisted radical prostatectomy (RARP) was introduced early this decade by Galfano et al [1]. Interestingly, 90% and 96% of patients treated with Retzius‐sparing RARP (RS‐RARP) were continent (no pad/safety pad) at 1 week and 1 year, respectively. Similarly, our group reported a 70% continence rate (no pad) at 1 month after RS‐RARP [2].

The fast urinary continence recovery after RS‐RARP is related to several anatomical factors: the anterior Retzius space is kept intact; the urinary bladder is not dropped; the endopelvic fascia and puboprostatic ligaments are preserved; and there is minimal distortion of the supporting urethral tissues. A recent study reported [3] that less bladder neck descent was observed during postoperative cystogram in patients treated with RS‐RARP than in those treated with standard RARP.

In a recent randomized controlled study, the postoperative continence rate at 1 week was 48% in standard RARP compared with 71% in RS‐RARP (P = 0.01), and this difference was maintained at 3 months (86% standard RARP vs 95% RS‐RARP; P = 0.02). At 1 year, however, the effect on urinary continence difference was muted (93.3% standard RARP vs 98.3% RS‐RARP; P = 0.09) [4]. Similarly, Chang et al. [3] found that the higher continence rate at 1 week (73.3% RS‐RARP vs 26.7% standard RARP; P = 0.000) had vanished at 1 year (100% vs 93.3%; P = 0.15). By contrast, a large recent prospective series showed that the superiority of RS‐RARP in terms of higher early urinary continence was maintained at 1 year (97.5% RS‐RARP vs 68.5% standard RARP) [5].

In addition to a higher early continence rate, RS‐RARP has a lower incidence of postoperative inguinal hernia occurrence compared with standard RARP [6]. Theoretically, RS‐RARP may provide several other potential advantages. It may be advantageous if patients require future surgery necessitating access to the Retzius space and dropping of the bladder, such as an artificial urinary sphincter implantation, an inflatable penile prosthesis insertion, or kidney transplantation. In addition, in patients with previous inguinal hernia repair using mesh, it enables the avoidance of anterior adhesions by accessing the prostate directly from the Douglas pouch. Notably, large‐size glands and/or middle‐lobe, advanced/high‐risk PCa, and patients with previous prostatic surgeries can be managed safely with RS‐RARP in experienced hands.

Undoubtedly, oncological safety is our main concern in treating cancer. To determine the effectiveness of new treatment methods, long‐term follow‐up is warranted. Biochemical recurrence (BCR) is widely used as a primary oncological outcome to assess PCa treatment success. To our knowledge, after radical prostatectomy, ~35% of patients are at risk of developing BCR in the next 10 years. Currently, there are insufficient data regarding the oncological outcomes of RS‐RARP. Only four articles have compared early oncological outcomes between RS‐RARP and standard RARP, and there was no significant difference (Table 1).

More recently, we reported on the mid‐term oncological outcomes of 359 patients who underwent RS‐RARP. The median follow‐up was 26 months. Although this period is not long enough to reach a meaningful conclusion on the oncological safety of RS‐RARP, it is the longest follow‐up period reported in literature. Overall, the positive surgical margin (PSM) rate was 30.6% (14.6% in pT2 and 40.8% in pT3a disease) and the BCR rate was 14.8%. In terms of functional outcomes, the urinary continence rate at 1 year was 93.9% [7]. Interestingly, 164 patients (45.7%) of our cohort had high‐risk PCa. In these patients, the PSM rate was 41.2%, the BCR rate was 22%, and the 3‐year BCR‐free survival (BCRFS) rate was 72%. We compared our results with those in patients with high‐risk PCa treated with standard RARP in the literature. In studies that used the D’Amico criteria the median follow‐up ranged from 12.5 to 37.3 months, the PSM rates were 20.5% to 53.3%, the BCR rates were 17.4% to 31% and the 3‐year BCRFS rates were 41.4% to 86%. In studies that used the National Comprehensive Cancer Network criteria, the median follow‐up ranged from 23.6 to 27 months, the PSM rates were 29% to 38%, the BCR rates were 9.4% to 33%, and the 3‐year BCRFS rates were 55% to 66% [7].

In summary, RS‐RARP is a novel surgical approach which is associated with better urinary continence recovery in the first few months compared with standard RARP [2,3,4,5]. This superiority might be maintained [5] or equalized at 1 year [3,4]. A few studies have compared the early oncological results between RS‐RARP and standard RARP and no significant difference was found [2,3,4,5]. Recently, our group reported the mid‐term oncological outcomes of patients with high‐risk PCa treated with RS‐RARP and these were similar to those of large studies of conventional RARP. This confirms effective and safe mid‐term BCR control after RS‐RARP, while the long‐term oncological results are awaited [7]. Currently, >4 000 cases of RS‐RARP are performed worldwide and more centres are beginning to use and converting to Retzius‐sparing surgery. All centres are experiencing faster recovery of continence. Thanks are due to Drs Galfano and Bocciardi for exploring and sharing this surgical frontier.

 

References

  1. Galfano A, Di Trapani D, Sozzi F, et al. Beyond the learning curve of the Retzius‐sparing approach for robotassisted laparoscopic radical prostatectomy: oncologic and functional results of the first 200 patients with ? 1 year of follow‐up. Eur Urol 2013; 64: 974‐80
  2. Lim SK, Kim KH, Shin TY et al. Retzius‐sparing robot‐assisted laparoscopic radical prostatectomy: combining the best of retropubic and perineal approaches. BJU Int 2014; 114: 236–44
  3. Chang LW, Hung SC, Hu JC et al. Retzius‐sparing robotic‐assisted radical prostatectomy associated with less bladder neck descent and better early continence outcome. Anticancer Res 2018; 38: 345–51
  4. Menon M, Dalela D, Jamil M et al. Functional recovery, oncologic outcomes and postoperative complications after robot‐assisted radical prostatectomy: an evidence‐based analysis comparing the Retzius sparing and standard approaches. J Urol 2018; 199: 1210–7
  5. Sayyid RK, Simpson WG, Lu C et al. Retzius sparing robotic assisted laparoscopic radical prostatectomy: a safe surgical technique with superior continence outcomes. J Endourol 2017; 31: 1244–50
  6. Chang KD, Abdel Raheem A, Santok GDR et al. Anatomical Retzius‐space preservation is associated with lower incidence of postoperative inguinal hernia development after robot‐assisted radical prostatectomy. Hernia 2017; 21: 555–61
  7. Abdel Raheem A, Kidon C, Alenzi M et al. Predictors of biochemical recurrence after retzius‐sparing robot‐assisted radical prostatectomy: analysis of 359 cases with a median follow‐up of 26 months. Int J Urol 2018; 25: 1006–14

 

Resident’s podcast: Retzius‐sparing robot‐assisted radical prostatectomy

Maria Uloko is a Urology Resident at the University of Minnesota Hospital. In this podcast she discusses the following BJUI Article of the Week:

Retzius‐sparing robot‐assisted radical prostatectomy (RS‐RARP) vs standard RARP: it’s time for critical appraisal

Thomas Stonier*, Nick Simson*, John Davisand Ben Challacombe

 

*Department of Urology, Princess Alexandra Hospital, Harlow, Urology Centre, Guy s Hospital, London, UK and Department of Urology, MD Anderson Cancer Center, Houston, TX, USA

 

Abstract

Since robot‐assisted radical prostatectomy (RARP) started to be regularly performed in 2001, the procedure has typically followed the original retropubic approach, with incremental technical improvements in an attempt to improve outcomes. These include the running Van‐Velthoven anastomosis, posterior reconstruction or ‘Rocco stitch’, and cold ligation of the Santorini plexus/dorsal vein to maximise urethral length. In 2010, Bocciardi’s team in Milan proposed a novel posterior or ‘Retzius‐sparing’ RARP (RS‐RARP), mirroring the classic open perineal approach. This allows avoidance of supporting structures, such as the puboprostatic ligaments, endopelvic fascia, and Santorini plexus, preserving the normal anatomy as much as possible and limiting damage that may contribute to improved postoperative continence and erectile function. There has been much heralding of the excellent functional outcomes in both the medical and the lay press, but as yet no focus or real mention of any potential downsides of this new technique.

 

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Article of the Month: Use of machine learning to predict early biochemical recurrence after robot‐assisted prostatectomy

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.

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

Use of machine learning to predict early biochemical recurrence after robot‐assisted prostatectomy

Nathan C. Wong , Cameron Lam, Lisa Patterson and Bobby Shayegan
Division of Urology, Department of Surgery, McMaster University, Hamilton, ON, Canada

Visual abstract created Rebecca Fisher @beckybeckyfish

Abstract

Objectives

To train and compare machine‐learning algorithms with traditional regression analysis for the prediction of early biochemical recurrence after robot‐assisted prostatectomy.

Patients and Methods

A prospectively collected dataset of 338 patients who underwent robot‐assisted prostatectomy for localized prostate cancer was examined. We used three supervised machine‐learning algorithms and 19 different training variables (demographic, clinical, imaging and operative data) in a hypothesis‐free manner to build models that could predict patients with biochemical recurrence at 1 year. We also performed traditional Cox regression analysis for comparison.

= 0.686) and with a univariate regression model (AUC = 0.865).

Results

K‐nearest neighbour, logistic regression and random forest classifier were used as machine‐learning models. Classic Cox regression analysis had an area under the curve (AUC) of 0.865 for the prediction of biochemical recurrence. All three of our machine‐learning models (K‐nearest neighbour (AUC 0.903), random forest tree (AUC 0.924) and logistic regression (AUC 0.940) outperformed the conventional statistical regression model. Accuracy prediction scores for K‐nearest neighbour, random forest tree and logistic regression were 0.976, 0.953 and 0.976, respectively.

Conclusions

Machine‐learning techniques can produce accurate disease predictability better that traditional statistical regression. These tools may prove clinically useful for the automated prediction of patients who develop early biochemical recurrence after robot‐assisted prostatectomy. For these patients, appropriate individualized treatment options can improve outcomes and quality of life.

Editorial: Can machine‐learning algorithms replace conventional statistics?

Wong et al. [1] evaluate 19 clinical variables (training data) and three supervised machine‐learning algorithms to predict early biochemical recurrence after robot‐assisted prostatectomy. They further compare the areas under the curve (AUCs) resulting from these algorithms with the AUC of a conventional Cox regression model and conclude that the machine‐learning algorithms can produce accurate disease prognosis, perhaps better than a traditional Cox regression model. As the authors state, predictive models have the potential to better individualize care to patients at highest risk of prostate cancer recurrence and progression.

The authors should be commended for their adoption of machine‐learning algorithms to better interpret the vast volumes of clinical data and assess prognosis after robot‐assisted prostatectomy. This should represent another step forward for the management of prostate cancer, where tailored treatment is now largely based on the clinical risk stratification of the disease [2]. Incidentally, we are also in an era where we are seeing aspects of artificial intelligence (machine learning being a subset of it) vastly transform how we view and process data in everyday life. This has been true in medicine as well, particularly for prostate cancer [3].

While our own research group has also evaluated machine‐learning algorithms to process surgeon performance metrics and predict clinical outcomes after robot‐assisted prostatectomy [4], I want to express a word of caution. Utilization of machine learning does not in itself imply automatic superiority over conventional statistics [5] despite literature that has demonstrated so [3]. The success of predictive models in machine learning still relies on the quality of data introduced and careful execution of the analysis. In our experience, it works best when highly experienced clinicians and data scientists are working hand in hand.

Furthermore, I would argue that the results of this present study do not necessarily show that machine learning is superior to conventional statistics, but rather it highlights an inherent advantage of machine learning. While traditional analyses require the a priori selection of a model based on the available data, machine learning has more flexibility for model fitting [6]. Additionally, inclusion of variables in traditional analyses is constrained by the sample size. In contrast, by design, machine learning models thrive on their ability to consider many variables concurrently, and as such, have the potential to detect underlying patterns that may otherwise be undetectable when data are examined effectively in individual silos.

We look forward to the external validation of the methodology described in the present article. Big and diverse data are critical requirements of machine learning. A multi‐institutional, multi‐surgeon cohort is necessary to confirm the findings in this report. A further step from there is the adoption of such prediction models into clinical use. The ultimate question is how improved prognostic data may influence surgeon and patient decisions.

Conflict of Interest

Dr Hung reports personal fees from Ethicon, Inc, outside the submitted work.

References

  1. Wong NC, Lam C, Patterson L, Shayegan B. Use of machine learning to predict early biochemical recurrence following robotic prostatectomy. BJU Int 2019; 123: 51–7
  2. D’Amico AV, Whittington R, Malkowicz SB et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy or interstitial radiation therapy for clinically localized prostate cancer. JAMA 1998; 280: 969–74
  3. Hung AJ, Chen J, Che Z et al. Utilizing machine learning and automated performance metrics to evaluate robot‐assisted radical prostatectomy performance and predict outcomes. J Endourol 2018; 32: 438–445
  4. Kattan MW. Comparison of Cox regression with other methods for determining prediction models and nomograms. J Urol 2003; 170 (6 Pt 2): S6–9
  5. Hung AJ, Chen J, Gill IS. Automated performance metrics and machine learning algorithms to measure surgeon performance and anticipate clinical outcomes in robotic surgery. JAMA Surg 2018; 153: 770–1

RE: National implementation of multi-parametric MRI for prostate cancer detection – recommendations from a UK consensus meeting

Letter to the Editor

National implementation of multi-parametric magnetic resonance imaging for prostate cancer detection – recommendations from a UK consensus meeting [1]

Dear Sir,

Appaya et al report on an expert consensus meeting regarding the implementation of multi-parametric magnetic resonance imaging (mpMRI) for prostate cancer detection [1]. A key item related to ‘who can request an mpMRI’ for patients with suspicion of prostate cancer. The panel unanimously agreed that GPs should not be able to. This is perhaps unsurprising, given the panel was composed entirely of specialists. The authors did consider inviting a GP: however, their assumption was that other than for this question a GP would have little to add. We believe this was a critical omission, as improving access to diagnostic testing in primary care could improve prostate cancer diagnosis,  urology outpatient workloads, patient experiences, and outcomes.

The vast majority of cancer diagnoses, including prostate, occur in symptomatic patients presenting to primary care [2]. GPs already have direct access to diagnostic testing for several other cancer types in the NHS – all endorsed by NICE guidance – including gastroscopy, colonoscopy, flexible sigmoidoscopy, MRI head, ultrasound, and CT abdomen. Each can be requested in primary care, with GPs retaining clinical responsibility for the investigation findings [3].

An oft-raised concern with GP direct access to diagnostic tests is that it will lead to inappropriate referrals. However, a recent systematic review of direct access cancer testing in primary care found no significant difference in pooled cancer conversion rate between GP and specialist requests (except for gastroscopy) and no significant difference in the appropriateness of referrals. Time from referral to testing was shorter with GP direct access testing and patient satisfaction was high [4].

If implementation of pre-biopsy mpMRI truly does reduce the need for biopsy in 27% of men, as suggested from the PROMIS [5] and PRECISION [6] trials, then direct access testing in primary care could significantly reduce referrals for suspected prostate cancer. At a time of limited NHS resources and more ambitious targets for cancer diagnosis and treatment times, this could ease the pressure on Urology departments across the UK.

There are several unanswered questions with regard to the optimal use of pre-biopsy mpMRI: for example, which men to test, how to safely follow-up mpMRI-negative patients, and MRI capacity. Including GPs in these discussions would not just be courteous: it may find better answers.

Dr Samuel Merriel1, Dr Fiona Walter2, Prof Willie Hamilton3

Clinical Research Fellow, University of Exeter

2 Principle Researcher in Primary Care Cancer Research, University of Cambridge

3 Professor of Primary Care Diagnostics, University of Exeter

References

  1. Appayya MB, Adshead J, Ahmed HU, Allen C, Bainbridge A, Barrett T, et al. National implementation of multi-parametric magnetic resonance imaging for prostate cancer detection – recommendations from a UK consensus meeting. BJU Int. 2018;122(1):13–25.
  2. Emery JD, Shaw K, Williams B. The role of primary care in early detection and follow-up of cancer. Nat Rev Clin Oncol. 2014;11:38–48.
  3. National Collaborating Centre for Cancer. Suspected cancer [Internet]. NICE. London; 2015.
  4. Smith CF, Tompson AC, Jones N, Brewin J, Spencer EA, Bankhead CR, et al. Direct access cancer testing in primary care: a systematic review of use and clinical outcomes. Br J Gen Pract. 2018;(August):1–10.
  5. Ahmed HU, El-Shater Bosaily A, Brown LC, Gabe R, Kaplan R, Parmar MK, et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet [Internet]. 2017;389(10071):815–22.
  6. Kasivisvanathan V, Rannikko AS, Borghi M, Panebianco V, Mynderse LA, Vaarala MH, et al. MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis. N Engl J Med [Internet]. 2018.

Reply by the authors

I thank Dr Samuel Merriel and Dr Fiona Walter for writing in about the role of the GP in requesting prostate MRI studies. Indeed, we reported that our consensus panel unanimously agreed that GPs should not be requesting prostate MRI studies [1]. Their letter in follow-up of this offers an opportunity to explain further this recommendation.

We adopted a UCL-RAND based methodology to conduct the consensus meeting. Whilst we would have liked to have broader representation on the panel, one of the key metrics necessitates that a minimum proportion of participants be able to answer a particular question for that question to be valid. Further broadening of the panel risked delivery of this.

Nonetheless, we agree that GP representation in designing and implementing healthcare is invaluable and should not be ignored and could have all of the benefits for prostate cancer diagnostics that are pointed out by Dr Merriel and Dr Walter.

To clarify the consensus panels discussion on this topic; the panel felt that within the current climate there remained many areas that needed standardisation and improvement if we are to realise the benefits highlighted in PROMIS [2] and PRECISION [3] e.g. diagnostic quality of scans, training of radiologists to report scans all the way through to a consensus from urologists of how to manage patients with a specific scan result.  The panel did not believe that GPs were incapable of managing direct referral services for prostate MRI, only that this needed to be introduced in a controlled fashion if we were to be successful in implementing multi-parametric MRI whilst maintaining its performance and value. The panel felt that direct GP referral should therefore be re-discussed once mechanisms to maintain scan quality and standards of reporting were realised across the UK.

Indeed, GPs should be included in the discussion of which men to test, how to follow-up mp-MRI negative patients and those related to MRI capacity – all of these assume that one is looking at a test that is correctly set-up and reported to a specific standard. Perhaps a consensus on management of patients amongst urologists and primary care physicians is a warranted next step.

Shonit Punwani1

1Centre for Medical Imaging, University College London, UK.

References

  1. Appayya MB, Adshead J, Ahmed HU et al. National implementation of multi-parametric magnetic resonance imaging for prostate cancer detection – recommendations from a UK consensus meeting. BJU Int 2018; 122:13-25.
  2. Ahmed HU, El-Shater Bosaily A, Brown LC, Gabe R, Kaplan R, Parmar MK, et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet [Internet]. 2017;389(10071):815–22.
  3. Kasivisvanathan V, Rannikko AS, Borghi M, Panebianco V, Mynderse LA, Vaarala MH, et al. MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis. N Engl J Med [Internet]. 2018.

 

 

RE: National implementation of multi-parametric MRI for prostate cancer detection – recommendations from a UK consensus meeting

Letter to the Editor

National implementation of multi-parametric magnetic resonance imaging for prostate cancer detection – recommendations from a UK consensus meeting [1]

Dear Sir,

We congratulate the authors for their efforts in standardising prostate mpMRI. However, we are concerned that the consensus as reported may place substantial pressure on the diagnostic pathway in a rapidly evolving field. Most departments in the West of Scotland and the UK are striving to offer a routine pre-biopsy MRI service, witnessing doubling of the demand on scanning and radiologist time [2], aggravating the nationwide shortage of radiologists [3].

A standard reporting system is vital to the consistent implementation of diagnostic pathways. PI-RADS version 2 focuses on the standardisation of reading, setting out where and when to use each sequence, and has been widely implemented [4]. This, however, has taken time and its learning curve is ongoing within local hospitals [5]. Its main advantage over a clinico-radiological Likert impression is the reduced flexibility of interpretation of radiological parameters, giving those gaining experience in the field a clear set of definitions to work to. We are concerned that enforcing a second system so quickly will discourage radiologists during their learning curves. The panel is entirely correct in stating that even with the use of Likert system, the reporting will be influenced by PI-RADS criteria. While the urology and uro-radiology communities have widely embraced PI-RAD reporting, official switch to Likert reporting may introduce unnecessary reporting subjectivity before individual radiologists are fully experienced with the use of PI-RADS. Furthermore, with the expectation of PI-RADS v3 in the near future, it may be better to adopt PI-RADS v2 now, and compare PI-RADS v3 and Likert system in due course.

The panel describes dynamic contrast enhancement (DCE) as essential component and we agree that mpMRI incorporating the use of contrast is well established, with particular impact on the distinction between PIRADS 3 and 4 lesions. However, a short 9 minute biparameteric MR protocol was as good as a longer and more elaborate protocol using DCE in detecting clinically significant prostate cancer [6]. In NHS Greater Glasgow and Clyde (NHSGGC), we adopted a pragmatic approach, selecting patients for whom contrast may be particularly informative, i.e. those with hip replacement surgery and those who had previous negative biopsies. A contrast MRI prostate scan takes at least 10 minutes longer, and requires nominated radiologist supervision, reducing the overall capacity by 20%. In a 12 month period (2017-2018), 2,333 diagnostic MR prostate scans (20% with contrast) were performed within NHSGGC. For full adoption of contrast prostate MR, it will be necessary to increase the imaging capacity by ~100 supervised imaging lists per annum. Pharmacokinetic modelled DCE parameters (and not visually inspected start of enhancement) have the greatest potential to detect aggressive disease [7,8]. However this approach is currently not deemed feasible for widespread UK use, due to the lack of suitable standardized software.

In summary, we welcome the consensus recommendations for a unified prostate cancer imaging diagnostic strategy, but propose a pragmatic evolving approach that is sympathetic to the constraints of local and regional resources, both in terms of imaging capacity and uro-radiology reporting expertise.

Elizabeth Day1, Amit Patel2, John Morrison2, Thomas Hambrock3, Hing Y Leung1,4

1 Department of Urology, NHS Greater Glasgow and Clyde, Glasgow, G12 0XH

2 Department of Radiology, NHS Greater Glasgow and Clyde, Glasgow, G12 0XH

3 Department of Radiology, The Christie NHS Foundation Trust, Manchester M20 4BX

4 CRUK Beatson Institute for Cancer Research, Glasgow G61 1BD

 

References

  1. Appayya MB, Adshead J, Ahmed HU et al. National implementation of multi-parametric magnetic resonance imaging for prostate cancer detection – recommendations from a UK consensus meeting. BJU Int 2018; 122:13-25.
  2. Day E, Nalagatla S, Shin JS et al. Triaging patients to primary biopsy or prostate MRI based on digital rectal examination improves the detection rate of TRUS biopsy and avoids unnecessary biopsies. JCU 2018.
  3. The Royal College of Radiologists. Scottish patients at risk from radiologist shortages. 2018.
  4. Padhani AR, Weinreb J, Rosenkrantz AB et al. Prostate Imaging-Reporting and Data System Steering Committee: PI-RADS v2 Status Update and Future Directions. Eur Urol 2018.
  5. Hansen NL, Koo BC, Gallagher FA et al. Comparison of initial and tertiary centre second opinion reads of multiparametric magnetic resonance imaging of the prostate prior to repeat biopsy. Eur Radiol 2017; 27:2259-2266.
  6. Kuhl CK, Bruhn R, Krämer N et al. Abbreviated Biparametric Prostate MR Imaging in Men with Elevated Prostate-specific Antigen. Radiology 2017; 285:493-505.
  7. Vos EK, Litjens GJ, Kobus T et al. Assessment of prostate cancer aggressiveness using dynamic contrast-enhanced magnetic resonance imaging at 3 T. Eur Urol 2013; 64:448-55.
  8. Hambrock T, Vos P, Hulsbergen-van de Kaa C et al. Prostate cancer: computer-aided diagnosis with multiparametric 3-T MR imaging–effect on observer performance. Radiology 2013; 266:521-30

Reply by the authors

I read with great interest the letter composed by Day et al regarding our article: National implementation of multi-parametric magnetic resonance imaging for prostate cancer detection – recommendations from a UK consensus meeting (Appayya et al [1]).

The authors of the letter highlight several important points that were indeed discussed in detail at the consensus meeting.

The first being the pressure on diagnostic services that is expected to result from the implementation of a strategy adopting multi-parametric MRI prior to biopsy. We concur that there is a real risk that without additional funding and the specific training of specialist radiologists in prostate MRI, our aspirations to implement pre-biopsy MR will meet limited success. The consensus panel did agree that this remains an area where national support and prioritisation will be a key driver of success or failure.

The second point raised by Day et al was in regard to recommendation for the use of Likert verses PI-RADS version 2 reporting systems. This again was a well debated item at the consensus meeting. To clarify the consensus discussion, the panel felt that the PI-RADS v2 system was a good system to use when training to report prostate MRI, specifically as it has a very rigid set of definitions. Indeed, the intention of the panel in recommending Likert reporting was not to disregard the PI-RADS system, but to highlight that when sufficiently experienced we also use other factors in scoring that were not as yet incorporated into PI-RADS v2. Indeed, many experienced radiologists knowingly/unknowingly do not adhere to strict PI-RADS v2 scoring. For example, PI-RADS v2 recommends that clinical details (including PSA) should not influence interpretation yet it is almost ubiquitous that we report in light of the PSA and are now recommending PSA density measures to help us guide practice. Furthermore, many centres in the UK do not perform DCE MRI, yet report score as a PI-RADS v2– although DCE MRI as Day et al point out is a key component of the PI-RADS v2 scoring system. Any reports produced for patients that have had previous treatment cannot be scored by PI-RADS v2 criteria, yet there are ongoing examples of radiologists stating a PI-RADS v2 score within such reports.

In reality, Day et al are correct in pointing out that PI-RADS v3 may indeed resolve many of these issues.  PI-RADS v3 was not as far developed when the consensus meeting took place.

With regard to a bi-parametric verses multi-parametric approach; I would agree that most significant tumours will be detected with a bi-parametric MRI and that it will be a small minority that would benefit from DCE MRI. The difficulty to date has been that DCE MRI applications are very varied across studies and have generally concentrated on the use of pharmacokinetic parameters – which has limited studies looking at the value of DCE-MRI. Indeed, such protocols are difficult to themselves apply. The panel felt that a high resolution short DCE protocol that lasted 3 minutes could be implemented with visual inspection of the early arterial phase image for the detection of early enhancement indicative tumour. They also acknowledged that further research is required to establish the benefits of DCE MRI.

I would like to thank Day et al for their letter, as it is important to highlight these areas from the consensus paper in order (i) to recognise where national support is required, (ii) to help clarify any areas which more detailed description could not be provided within the paper, and (iii) to continue to recognise areas where research and further technique refinement is required.

Shonit Punwani1

1Centre for Medical Imaging, University College London, UK.

References

  1. Appayya MB, Adshead J, Ahmed HU et al. National implementation of multi-parametric magnetic resonance imaging for prostate cancer detection – recommendations from a UK consensus meeting. BJU Int 2018; 122:13-25.

 

 

Article of the week: Does the introduction of prostate multi-parametric MRI into the AS protocol for localized PCa improve patient re-classification?

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

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

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

Does the introduction of prostate multiparametric magnetic resonance imaging into the active surveillance protocol for localized prostate cancer improve patient re-classification?

Richard J. Bryant*† , Bob Yang* , Yiannis Philippou*, Karla Lam*, Maureen Obiakor*, Jennifer Ayers*, Virginia Chiocchia†‡, Fergus Gleeson§, Ruth MacPherson§, Clare Verrill†¶, Prasanna Sooriakumaran†**, Freddie C. Hamdy*† and Simon F. Brewster*

*Department of Urology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK, †Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK, ‡National Perinatal Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK, §Department of Radiology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK, Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK, and **Department of Uro-Oncology, University College London Hospital NHS Foundation Trust, London, UK

Abstract

Objectives

To determine whether replacement of protocol‐driven repeat prostate biopsy (PB) with multiparametric magnetic resonance imaging (mpMRI) ± repeat targeted prostate biopsy (TB) when evaluating men on active surveillance (AS) for low‐volume, low‐ to intermediate‐risk prostate cancer (PCa) altered the likelihood of or time to treatment, or reduced the number of repeat biopsies required to trigger treatment.

Patients and Methods

A total of 445 patients underwent AS in the period 2010–2016 at our institution, with a median (interquartile range [IQR]) follow‐up of 2.4 (1.2–3.7) years. Up to 2014, patients followed a ‘pre‐2014’ AS protocol, which incorporated PB, and subsequently, according to the 2014 National Institute for Health and Care Excellence (NICE) guidelines, patients followed a ‘2014–present’ AS protocol that included mpMRI. We identified four groups of patients within the cohort: ‘no mpMRI and no PB’; ‘PB alone’; ‘mpMRI ± TB’; and ‘PB and mpMRI ± TB’. Kaplan–Meier plots and log‐rank tests were used to compare groups.

Results

Of 445 patients, 132 (30%) discontinued AS and underwent treatment intervention, with a median (IQR) time to treatment of 1.55 (0.71–2.4) years. The commonest trigger for treatment was PCa upgrading after mpMRI and TB (43/132 patients, 29%). No significant difference was observed in the time at which patients receiving a PB alone or receiving mpMRI ± TB discontinued AS to undergo treatment (median 1.9 vs 1.33 years; P = 0.747). Considering only those patients who underwent repeat biopsy, a greater proportion of patients receiving TB after mpMRI discontinued AS compared with those receiving PB alone (29/66 [44%] vs 32/87 [37%]; P = 0.003). On average, a single set of repeat biopsies was needed to trigger treatment regardless of whether this was a PB or TB.

Conclusion

Replacing a systematic PB with mpMRI ±TB as part of an AS protocol increased the likelihood of re‐classifying patients on AS and identifying men with clinically significant disease requiring treatment. mpMRI ±TB as part of AS thereby represents a significant advance in the oncological safety of the AS protocol.

 

Editorial: Multi-parametric MRI: an important tool to improve risk stratification for active surveillance in prostate cancer

Multiparametric MRI (mpMRI) has become an important adjunct in the management of localized prostate cancer (PCa), particularly in the active surveillance (AS) setting. Current guideline recommendations [1,2] have recommended incorporation of mpMRI into AS protocols to improve patient stratification and reclassification.

Bryant et al. [3], based on updated National Institute of Health and Care Excellence (NICE) guidelines [1], report on the effect of mpMRI incorporation into their institution’s AS protocols, specifically focusing on the time to treatment and number of biopsies required to trigger treatment. In 2014, they replaced protocol‐driven biannual prostate biopsies (PBs) with mpMRI ± cognitive targeted biopsy and systematic biopsy (TB). With a median follow‐up of 2.4 years, they found that more men who underwent TB progressed to treatment than men who underwent PB alone (44% vs 37%; P = 0.003). The median number of biopsies (beyond the original diagnostic biopsy) required to trigger intervention was 1.55. Based on these results, the authors conclude that mpMRI‐driven TB increases reclassification compared with protocol‐driven PB.

This is consistent with increasing evidence that mpMRI enhances, and sometimes, exceeds detection of clinically significant PCa over TRUS‐guided prostate biopsy alone. The PROMIS study [4], a multicentre paired validation study that compared mpMRI to TRUS‐guided biopsy in the diagnostic setting, found that mpMRI had better sensitivity (93% vs 43%; P < 0.001) and negative predictive value (89% vs 74%; P < 0.001) than TRUS‐guided biopsy in detecting clinically significant cancer (defined as Gleason grade ≥4 + 3). While the concerns about foregoing a systematic biopsy at the time of targeted biopsy in that study were warranted, there was consensus that prebiopsy mpMRI increased the yield for clinically significant PCa.

In the AS setting, unfortunately, randomized data are lacking; however, retrospective series and systematic reviews provide some guidance. In a systematic review, Schoots et al. [5] found that a positive mpMRI in the AS setting was associated with a higher risk of upgrading at the time of radical prostatectomy and a higher risk of reclassification at the time of confirmatory biopsy. Yet, a negative mpMRI did not preclude reclassification and upgrading, indicating the continued need for systematic biopsy. Recabal et al. [6] confirmed these conclusions in their retrospective assessment of an institutionally maintained prospective dataset. While MRI‐targeted biopsies detected higher grade cancer in 23% of men, they missed higher grade clinically significant cancers in 17%, 12% and 10% of patients with mpMRI scores of 3, 4 and 5, respectively. This suggests that both targeted and systematic biopsy should be used for the optimal detection of clinically significant PCa in men on AS.

The present study by Bryant et al. [3] reaffirms the value of mpMRI in the AS paradigm. Yet, some concerns about their study cohort and methodology should be noted. First, as the authors clearly note as a limitation, despite completing a targeted and systematic biopsy, all the samples were sent as a single specimen, precluding the ability to distinguish between targeted biopsy and systematic biopsy cores. As the absolute difference in the rate of progression to treatment between the PB and TB arms was only 7%, it is uncertain how much of that was attributable to the addition of targeted biopsy alone.

Additionally, in a closer analysis of their study population, it should be noted that 35% of the patients had Gleason Grade Group 2 disease or higher at the time of inclusion, representing a higher‐risk AS patient population than guideline recommendations. This may account for the higher rate of progression to treatment in this study cohort independent of grade progression – 24% of patients progressed to treatment based on PSA progression alone and an additional 10% were based on mpMRI findings alone.

Lastly, the median number of biopsies required to trigger intervention was 1.55 and, for the majority of patients, this was just one additional biopsy beyond the original diagnostic biopsy. Guideline recommendations indicate the importance of a confirmatory biopsy to exclude Gleason sampling error [2]; however, by definition, many of these patients were essentially upstaged or redirected to active treatment after a confirmatory biopsy. With 59% of the entire AS population never receiving a confirmatory biopsy beyond their original diagnostic biopsy and many progressing to treatment after a confirmatory biopsy, this study population may not reflect a well‐selected low‐risk PCa patient population for AS.

Despite these limitations, the work by Bryant et al. [3] adds to the growing body of evidence supporting the use of mpMRI‐targeted biopsies in addition to systematic biopsy to more accurately risk stratify men for AS, particularly at the time of diagnosis. It remains unknown how we can use mpMRI to individually tailor surveillance strategies or if mpMRI may ultimately replace surveillance biopsies over time.

References

  1. Graham J, Kirkbride P, Cann K, Hasler E, Prettyjohns M. Prostate cancer: summary of updated NICE guidance. BMJ (Clinical research ed.). 2014348: f7524
  2. Mottet N, Bellmunt J, Bolla M et al. EAU‐ESTRO‐SIOG Guidelines on Prostate Cancer. Part 1: screening, diagnosis, and local treatment with curative intentEur Urol 201771: 618–29

 

Article of the week: Urinary, bowel and sexual health in older men from Northern Ireland

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. There is also a video produced by the authors, and a podcast created by our Resident podcasters Giulia Lane and Maria Uloko.

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

Urinary, bowel and sexual health in older men from Northern Ireland

David W. Donnelly*, Conan Donnelly†, Therese Kearney*, David Weller‡, Linda Sharp§, Amy Downing¶, Sarah Wilding¶, PennyWright¶, Paul Kind**, James W.F. Catto††, William R. Cross‡‡, Malcolm D. Mason§§, Eilis McCaughan¶¶, Richard Wagland***, Eila Watson†††, Rebecca Mottram¶, Majorie Allen, Hugh Butcher‡‡‡, Luke Hounsome§§§, Peter Selby, Dyfed Huws¶¶¶, David H. Brewster****, EmmaMcNair****, Carol Rivas††††, Johana Nayoan***, Mike Horton‡‡‡‡, Lauren Matheson†††, Adam W. Glaser and Anna Gavin*

*Northern Ireland Cancer Registry, Centre for Public Health, Queen’s University Belfast, Belfast, UK, †National Cancer Registry Ireland, Cork, Ireland, ‡Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK, §Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK, Leeds Institute of Cancer and Pathology/Leeds Institute of Data Analytics, University of Leeds, Leeds, UK, **Institute of Health Sciences, University of Leeds, Leeds, UK, ††Academic Urology Unit, University of Sheffield, Sheffield, UK, ‡‡Department of Urology, St James’s University Hospital, Leeds, UK, §§Division of Cancer and Genetics, School of Medicine, Velindre Hospital, Cardiff University, Cardiff, UK, ¶¶Institute of Nursing and Health Research, Ulster University, Coleraine, UK, ***Faculty of Health Sciences, University of Southampton, Southampton, UK, †††Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, UK, ‡‡‡Yorkshire Cancer Patient Forum, c/o Strategic Clinical Network and Senate, Yorkshire and The Humber, Harrogate, UK, §§§National Cancer Registration and Analysis Service, Public Health England, Bristol, UK, ¶¶¶Welsh Cancer Intelligence and Surveillance Unit, Cardiff, UK, ****Information Services Division, NHS National Services Scotland, Edinburgh, UK, ††††Department of Social Science, UCL Institute of Education, University College London, London, UK, and ‡‡‡‡Psychometric Laboratory for Health Sciences, Academic Department of Rehabilitation Medicine, University of Leeds, Leeds, UK

Abstract

 Objectives

To provide data on the prevalence of urinary, bowel and sexual dysfunction in Northern Ireland (NI), to act as a baseline for studies of prostate cancer outcomes and to aid service provision within the general population.

Subjects and Methods

A cross‐sectional postal survey of 10 000 men aged ≥40 years in NI was conducted and age‐matched to the distribution of men living with prostate cancer. The EuroQoL five Dimensions five Levels (EQ‐5D‐5L) and 26‐item Expanded Prostate Cancer Composite (EPIC‐26) instruments were used to enable comparisons with prostate cancer outcome studies. Whilst representative of the prostate cancer survivor population, the age‐distribution of the sample differs from the general population, thus data were generalised to the NI population by excluding those aged 40–59 years and applying survey weights. Results are presented as proportions reporting problems along with mean composite scores, with differences by respondent characteristics assessed using chi‐squared tests, analysis of variance, and multivariable log‐linear regression.

Results

Amongst men aged ≥60 years, 32.8% reported sexual dysfunction, 9.3% urinary dysfunction, and 6.5% bowel dysfunction. In all, 38.1% reported at least one problem and 2.1% all three. Worse outcome was associated with increasing number of long‐term conditions, low physical activity, and higher body mass index (BMI). Urinary incontinence, urinary irritation/obstruction, and sexual dysfunction increased with age; whilst urinary incontinence, bowel, and sexual dysfunction were more common among the unemployed.

Conclusion

These data provide an insight into sensitive issues seldom reported by elderly men, which result in poor general health, but could be addressed given adequate service provision. The relationship between these problems, raised BMI and low physical activity offers the prospect of additional health gain by addressing public health issues such as obesity. The results provide essential contemporary population data against which outcomes for those living with prostate cancer can be compared. They will facilitate greater understanding of the true impact of specific treatments such as surgical interventions, pelvic radiation or androgen‐deprivation therapy.

 

Article of the week: RP and the effect of close surgical margins: results from the SEARCH database

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

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

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

Radical prostatectomy and the effect of close surgical margins: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database

Christine Herforth*, Sean P. Stroup*†‡, Zinan Chen§¶, Lauren E. Howard§¶, Stephen J. Freedland¶†††, Daniel M. Moreira***, Martha K. Terris§¶, William J. Aronson**††, Matthew R. Cooperberg‡§§, Christopher L. Amling¶¶ and Christopher J. Kane†‡‡‡

 

*Department of Urology, Naval Medical Center San Diego, Department of Urology, University of California, San Diego, Section of Urologic Oncology, Moores UCSD Cancer Center, ‡‡‡Veterans Affairs San Diego Medical Center, La Jolla, **University of California, ††Veteran Affairs Los Angeles, †††Cedars-Sinai Medical Center, Los Angeles, ‡‡University of California, §§Veterans Affairs San Francisco Medical Center, San Francisco, CA, §Duke University, Veterans Affairs Durham Medical Center, Durham, NC, ¶¶Oregon Health and Science University, Portland, OR and ***The Mayo Clinic, Rochester, MN, USA

Abstract

Objective

To evaluate biochemical recurrence (BCR) patterns amongst men undergoing radical prostatectomy (RP) with specimens having negative (NSM), positive (PSM), and close surgical margins (CSM) from the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort, as PSM after RP are a significant predictor of biochemical failure and possible disease progression, with CSM representing a diagnostic challenge for surgeons.

Patients and Methods

Men undergoing RP between 1988 and 2015 with known final pathological margin status were evaluated. The cohort was divided into three groups based on margin status; NSM, PSM, and CSM. CSM were defined by distance of tumour ≤1 mm from the surgical margin. BCR was defined as a prostate‐specific antigen (PSA) level of >0.2 ng/mL, two values at 0.2 ng/mL, or secondary treatment for an elevated PSA level. Predictors of BCR, metastases, and mortality were analysed using Cox proportional hazard models.

 

Results

Of 5515 men in the SEARCH database, 4337 (79%) men met criteria for inclusion in the analysis. Of these, 2063 (48%) had NSM, 1902 (44%) had PSM, and 372 (8%) had CSM. On multivariable analysis, relative to NSM, men with CSM had a higher risk of BCR (hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.25–1.82; P < 0.001) but a decreased risk of BCR when compared to those men with PSM (HR 2.09, 95% CI 1.86–2.36; P < 0.001). Metastases, prostate cancer‐specific mortality and all‐cause mortality did not differ based on margin status alone.

Conclusions

Management of men with CSM is a diagnostic challenge, with a disease course that is not entirely benign. The evaluation of other known risk factors probably provides greater prognostic value for these men and may ultimately better select those who may benefit from adjuvant therapy.

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