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New Gleason grading system: Statement from the Editors of six journals

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The International Society of Urologic Pathology (ISUP) has completed a consensus process to modify and clarify the Gleason scoring system for prostate cancers (1). Five grade groups have been defined with tumors of ISUP Grade Group 1 being the least aggressive and having the lowest likelihood of progression, whereas those of ISUP Grade Group 5 have the highest likelihood of early systemic spread. This new system provides clearer guidance for pathologists to classify cancers on the basis of gland morphology, and it aligns better with contemporary management including active surveillance.

The editors of the major uro-oncology journals believe this is a helpful change for clinicians, researchers, and patients alike and are eager to help this system establish itself in the reporting of pathologic grade. To that end we are now asking investigators to use the ISUP system in the reporting of prostate cancers in their publications. As the grade groups correspond largely with current Gleason scores 6, 3+4, 4+3, 8, 9 and 10, the translation should be relatively simple. Over the next one to two years, side-by-side reporting of old and new histology may temporarily be necessary. We do recognize that some institutional and national databases are not set up to make the translation and exceptions will be granted in these cases.

Anthony Zietman MD
International Journal of Radiation Oncology Biology Physics

Joseph Smith MD
Journal of Urology

Eric Klein MD
Urology

Michael Droller MD
Urologic Oncology

Prokar Dasgupta MSc MD FRCS
BJUI

James Catto MBChB PhD FRCS
European Urology

Reference

  1. Epstein JI, Egevad L, Amin MB et al. The 2014 International Society of Urological Pathology (ISUP) Consensus Conference of Gleason Grading of Prostatic Carcinoma. Am. J. Surg. Pathol. 2016, 40: 244-252.

 

 

 

Where we are with screening and risk prediction for prostate cancer in 2016

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March Editorial ImageThe rate of PSA-based screening over the last 35 years can be compared with driving your car from the Netherlands to Italy. It starts with a rather flat drive, perhaps a few hills in the Southern part of the Netherlands, which represents the rate of PSA screening in the late 1980s. Moving with high speed through Germany, one gradually climbs to higher altitudes, i.e. the rate of PSA testing in the 1990s. Then the high (but very difficult to drive) summits and beautiful valleys of Switzerland are there, representing PSA testing practices in the new millennium and the decline in metastatic disease and related mortality [1]. Finally, we descend to Italy’s Po valley, comparable to PSA testing rates, especially in the USA after the recommendations of the USA Preventive Services Task Force [2,3].
The question is what will we do next? Will we take a left turn and slowly disappear into the sea like Venice? That is, returning to a situation where one out of two or three men died from their prostate cancer? [4] Or will we stop our car, look behind, see the beautiful landscape and return taking the Gotthard road tunnel, avoiding spillage of petrol (i.e. unnecessary PSA testing and potentially harmful prostate biopsies) and go straight to the valleys of Switzerland?
The first option is obviously not the way to go. Unfortunately, the recommendation to stop the use of the PSA test as a screening tool is a direct consequence of the rapid and uncontrolled uptake of the test, often followed by a random biopsy resulting in over-diagnosis and subsequent overtreatment. However, there are ample tools available to turn this situation around and reduce the negative effects of prostate cancer screening [5,6].
An example of such an approach can be found in the publication of Poyet et al. [7] in this issue of BJUI. In this study, the investigators validated updated versions of two multivariate risk-prediction tools, i.e. prostate cancer risk calculators (RCs), in a cohort of 1996 men all biopsied (6-, 8- or 12-core random biopsy) on the basis of an elevated PSA level or abnormal DRE. The data showed that both RCs outperformed the PSA/ DRE-based strategy in reducing unnecessary testing, and in addition avoided over-diagnosis. As said, this approach is one of the many opportunities to reduce the negative aspects of PSA-based screening all summarised in the different guidelines [8]. Reading these guidelines, it soon becomes clear that it is known that repeatedly testing men with low PSA levels is useless. It is known that screening men with a limited life expectancy will only cause harm, and that simply repeating a prostate biopsy after a negative biopsy result (i.e. no prostate cancer detected) is not the way to go. And yet, this is what we see happening in daily clinical practice [9,10].
So, where are we with prostate cancer screening and risk prediction in 2016? We are in a situation that we know that we can reduce suffering and death from (metastatic) prostate cancer, with early detection and treatment, but that we have to selectively identify men that can actually benefit. The latter is realistic if we start to implement the knowledge we have acquired over recent decades.

 

Monique J. Roobol
Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands

 

References

 

1 Schroder FH, Hugosson J, Roobol MJ et al. Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. Lancet 2014; 384: 2027–35

 

2 Moyer VA; U.S. Preventive Services Task Force. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2012; 157: 120–34

 

3 Banerji JS, Wolff EM, Massman JD 3rd, Odem-Davis K, Porter CR, Corman JM. Prostate Needle Biopsy Outcomes in the Era of the U.S. Preventive Services Task Force Recommendation against Prostate Specific Antigen Based Screening. J Urol 2016; 195: 66–73

 

4 Hsing AW, Tsao L, Devesa SS. International trends and patterns of prostate cancer incidence and mortality. Int J Cancer 2000; 85: 60–7

 

5 Roobol MJ, Carlsson SV. Risk stratification in prostate cancer screening. Nat Rev Urol 2013; 10: 38–48

 

6 Emberton M. Doubling our precision of risk stratification in early prostate cancer: too good to be true? BJU Int 2016; 117: 8–9

 

7 Poyet C, Nieboer D, Bhindi B et al. Prostate cancer risk prediction using the novel versions of the European Randomised Study for Screening of Prostate Cancer (ERSPC) and Prostate Cancer Prevention Trial (PCPT) risk calculators: independent validation and comparison in a contemporary European cohort. BJU Int 2016; 117: 401–8

 

8 Loeb S. Guideline of guidelines: prostate cancer screening. BJU Int 2014; 114: 323–5

 

9 Nordstrom T, Aly M, Clements MS, Weibull CE , Adolfsson J, Gronberg H . Prostate-specific antigen (PSA) testing is prevalent and increasing in Stockholm County, Sweden, Despite no recommendations for PSA screening: results from a population-based study, 2003-2011. Eur Urol 2013; 63: 419–25

 

10 Drazer MW, Huo D, Eggener SE. National Prostate Cancer Screening Rates after the 2012 US Preventive Services Task Force recommendation discouraging prostate-specific antigen-based screening. J Clin Oncol 2015; 33: 2416– 23

 

Correction: The word “their” was added to this sentence to clarify its meaning: “That is, returning to a situation where one out of two or three men died from their prostate cancer? [4]”

 

 

What’s the Diagnosis?

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PQFeb3

Test yourself against our experts with our weekly quiz. You can type your answers here if you want to compare with our answers.

Image taken from Mafeld et al.

No such quiz/survey/poll

BJUI Knowledge – CPD on the move

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IMG_0531-Rob-Mills-2016-a2BJUI Knowledge is a new initiative for urologists, combining online CPD content together with a platform for recording CPD activity in one place. BJUI Knowledge, has been released this month to all BAUS members for a free trial period up until the end of June. It will be made available to all urologists later in 2016.

Once registered you will see we have already published around 60 CPD modules across 12 curriculum areas covering the breadth of urological practise. More modules will be added each month. We believe there will be something to enable all urologists to keep up to date. Some topics will be useful as a refresher and others may provide the opportunity for updating on contemporary issues. In times of appraisal and revalidation this venture provides both the opportunity to carry out CPD activity as well record and retrieve it as an annual report.

 

0592-video-image-v2The interactive e-learning modules have the accreditation of the Royal College of Surgeons of Edinburgh. The modules have been commissioned as manuscripts from authors with a genuine interest in the topic and then subjected to independent peer review. Each manuscript is converted into an online e-module with a standardised format including: learning objectives, knowledge checks, a final assessment and key learning points. Within the module, link is provided to the original manuscript as well as links to the abstracts for each reference in the manuscript.

0590-hotspot-imageWe will be adding to the modules available by 10-15 per month until we have created our full curriculum. Existing content will also be updated regularly to ensure it remains current. Access to the site may be by smart phone, tablet or desk top, and internet explorer 10 or equivalent is recommended for best functionality.

 

The e-learning content is optimised to be viewed on any kind of device, including a smartphone.

The CPD registration element allows:

1. Automatic registration of successfully completed BJUI Knowledge modules, although reflection (recommended for all CPD activity) may be added later.

2. Recording of other CPD activity under a variety of headings. (If we receive feedback that alternative headings are required we can add to the list available).

3. There is an app (accessed from the CPD page) which allows registration of CPD activity to your BJUI Knowledge account from your mobile phone while on the move. For example you may be visiting a department or at a meeting and take a photo which can be sent to your CPD account with details of the activity carried out.

4. At designated intervals, perhaps annually for appraisal, a complete record of CPD activity can easily be generated.

I would encourage you to use this exciting new resource and feed back to us with your comments to [email protected]

 

Rob Mills is the Editor of BJUI Knowledge

 

 

Importance of fundamental science as the cornerstone for translational research

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fwefwefResearch headlines that attract the most publicity are those that show success in benefitting patients, whether it is through new targeted drugs or new immunotherapies. Many funding bodies and charities have also changed their policy toward funding more translational research that has clear economic, clinical and patient benefit. We must remember, however, that the innovations for these transformative publications and translational research projects are imbedded in our fundamental understanding of the molecular and cellular biology of disease investigated at the basic science level. These investigations are the cornerstone of translational research.

 

The BJUI has continued its tradition of publishing fundamental research with translational insight, and this is exemplified in this month’s article by Liu et al. [1], which undertakes to explain the mechanistic and functional role of EZH2 in RCC. In this study the authors manipulate the expression of EZH2 by silencing it using short-hairpin EZH2, which targets the RNA. They also use a small molecule inhibitor of methyltransferase which has been shown to deplete the expression of EZH2. Both these approaches inhibit EZH2 expression, which was associated with reduced migration and invasion of the cancer cells, as assessed in in vitro models, as well as with slowing tumour growth and prolonging survival in an in vivo nude mouse model. These changes were mechanistically explained by a change in the mesenchymal epithelial transition phenotype of the tumour cells. The authors then went on to show that EZH2 is associated with E-cadherin suppression and poor survival in patients with RCC, demonstrating the translational importance of these findings.

 

This impo rtant fundamental and translational paper adds to the growing body of evidence that EZH2, which is a histone methyltransferase and regulator of gene expression, plays a key role in the development of a range of cancers including prostate, breast, lymphoma and colon [2]. 

 

The Translational Science section of the BJUI is looking for relevant and citable articles similar to the paper by Liu et al., which are imbedded in fundamental science and bring the concept into clinical investigation, either through its validation in clinical material or manipulation in clinically relevant in vivo model systems, and represent a clear translational step.

 

To facilitate our readers’ understanding and to familiarize them with often complicated and complex fundamental scientific concepts, in 2013 the BJUI introduced the ‘Science Made Simple’ review-type article section, in which various scientific concepts are explained so as to assist interactions between scientists and clinicians as they translate their ideas and findings into clinical utility.

 

References

 

1 Liu L, Xu Z, Zhong L et al. Enhancer of zeste homolog 2 (EZH2) promotes tumour cell migration and invasion via epigenetic repression of E-cadherin in renal cell carcinoma. BJU Int 2016; 117: 351–62

 

2 Simon JA, Lange CA. Roles of the EZH2 histone methyltransferase in cancer epigenetics. Mutat Res 2008; 647: 21–9

 

R. William Watson, BJUI Consulting Editor, Translational Science

 

UCD School of Medicine and Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland

 

The British Association of Urological Surgeons nephrectomy audit for T1 renal tumours

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It is hard to believe that 3 years have elapsed since my new team took over publishing the BJUI, aiming to make it ‘the most read surgical journal on the web’. Many of our readers believe that we have achieved that and a number of web statistics indicate that we are not far away. Complacency is not in our DNA and this year you will notice a number of subtle changes to www.bjui.org to make it even more attractive and user friendly. Of course we rely heavily on feedback from o ur authors and readers. The January 2016 issue includes our ‘Thank you to reviewers’ online, listing all 785 people who have reviewed for us in 2015. We just cannot achieve our high standards without you. Each reviewer is entitled to Continuing Professional Development (CPD) points as a recompense for the time they spend helping us select only the very best papers. 
Last year, we published a fantastic selection of ‘Articles of the Month’. If you missed any, you can find them collected together in our free online virtual issue (https://bit.ly/ZrWA6q). The end of 2015 was dominated by falling PSA testing and prostate cancer detection rates, as highlighted in David Penson’s editorial in JAMA [1]. In the UK and many other parts of the world we have already been through this. I remember during my training years that the majority of men presented with locally advanced or metastatic disease. And while we look towards ‘smart’ screening of high-risk groups, particularly those with a relevant family history of prostate and breast cancer, I urge you again to look at the summary table of our ‘Guideline of Guidelines’ by Loeb [2] on this thorny subject.
The BAUS has taken the lead on public reporting of surgical outcomes. The BJUI is proud to publish our nephrectomy audit [3], which has >6000 patients. Radical nephrectomy (RN) was performed mostly for T1b and partial nephrectomy (PN) for T1a tumours. Over 90% of RNs were minimally invasive – an established standard of care. Only 43% of PNs were minimally invasive of which one-third were robotic, with no obvious difference between the robotic and laparoscopic arms. As expected, the complication rates of PN were higher than RN. All of us as surgeons can learn a lot from large national datasets such as this and, more importantly, strive to improve continuously. I hope you enjoy reading this important paper and look forward to interacting with many of you in 2016.

 

References

1 Penson DF. The pendulum of prostate cancer screening. JAMA 2015; 314: 2031–3

 

2 Loeb S. Guideline of guidelines: prostate cancer screening. BJU Int 2014; 114: 323–5

 

3 Hadjipavlou M, Khan F, Fowler S et al. Partial vs radical nephrectomy for T1 renal tumours: an analysis from the British Association of Urological Surgeons Nephrectomy Audit. BJU Int 2015; 117: 62–71

 

Prokar Dasgupta, Editor-in-Chief, BJUI

 

King’s College London, Guy’s Hospital, London, UK

 

Should radiotherapy be a routine added-treatment for patients with N0,N+ non-metastatic prostate cancer on hormonal therapy?

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ISTOnce again we are approaching the end of another productive year in urological research. The final meeting of the year of the International Urology Journal Club #urojc was held from Monday December 7th to Wednesday December 8th AEDT. This month’s topic was a recent paper published in @JAMAOnc by the well-known STAMPEDE group.

In this new analysis of the STAMPEDE trial, the subject was the control arm. The trial’s definitive primary outcome was to evaluate the overall survival when adding radiotherapy (RT) to the cohort of N0 and N+ M0 high risk prostate cancer patients receiving hormonal therapy. The intermediate primary outcome was the failure-free survival (FFS), which was defined as biochemical failure, progression (locally, lymph nodes, or distant metastases) or death from prostate cancer.

The first comments of the discussion were about the satisfaction of a new study evaluating the beneficial effect of RT in addition to ADT in N+M0 disease. For the N0M0 Sub-cohort, 2 year survival was 97% (95% CI, 93%-99%), and 84% (95% CI, 74%-91%) were still alive after 5 years. On the other hand, for the N+M0 sub-cohort, 2 year survival was 93% (95% CI, 88%-96%), and 71% (95% CI, 56%-82%) were still alive after 5 years.

FFS was better with received RT in both groups: In the N0M0 sub-cohort the adjusted HR was 0.25 (95% CI, 0.13-0.49) with 2 year FFS of 96% (95% CI, 90%-98%) in patients receiving RT compared with 73% (95% CI, 57%-84%) in those not reporting RT (Figure). In the N+M0 the results were similar, with an adjusted HR of 0.35 (95% CI, 0.19-0.65), and a 2-year FFS of 89% (95% CI, 77%-94%) and 64% (95% CI, 51%-75%), respectively.

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Since this approach to high-risk N0,+ M0 disease is not a standard of treatment, there were some concerns about urologist opinions, and mainly, about the side-effects of pelvic radiation.

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This trial showed the adverse effects associated with RT, split by N0M0 and N+M0. The majority (78%) of N+M0 received conventionally fractionated RT to prostate and pelvis, and of the N0M0, 46% received it only to prostate and 42% to prostate and pelvis. The reported adverse effects were similar for patients with and without nodal involvement, with no grade 4 or 5 adverse effects reported.

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Another question during the discussion was about the control group and the different baseline characteristics of the patients if comparing to other countries (mainly previous surgery).

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Most urologists conclude that this information contributes to the growing evidence of the different modalities of treatment that should be offered to patients with prostate cancer. Every urologist focused on the importance of determining the risk and stage of the patient to give an appropriate treatment. They also mentioned how these results correlate with other treatment outcomes.

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The previous published trials about the subject conclude that this combination reduces the risk of prostate cancer death; however, the population of those studies varies. Most patients were low-risk N0M0 prostate cancer and none were N+M0.

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Other thoughts were shared, such as the usefulness of ADT for high-risk M0 prostate cancer, the prostate cancer stage and its relation to treatment response, and the needed collaboration of other specialties for study trials.

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We still have to remember that the study has some limitations, though: The study population is drawn from a control arm of a clinical trial. There is no randomization of patients, and those planned for radiotherapy were the ones considered fit for it, so there might be an overestimated benefit biased by a better prognosis.

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Indeed this is not the last of the STAMPEDE trials. One of the authors, @Prof_Nick_James mentioned redoing analysis of all the arms to evaluate more parameters about the outcomes of the different treatments.

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This topic raises many questions about the treatment approaches to high-risk prostate cancer. As the authors expressed “There is a need for randomized clinical trials within the N+M0 population to address questions prospectively”. So far the results shown seem to be of benefit, and support the routine use of radiotherapy in patients with N+M0 prostate cancer. But as usual, we always need more proof.

This is the last meeting of 2015, so I have to finish this summary with a “Merry Christmas and Happy New Year 2016” to all the Urological twitter family!

 

Irela Soto Troya is a urologist born and trained in the Republic of Panama, and is a Fellow at Severance Hospital/Yonsei Medical Health System, Seoul, South Korea.
Twitter @irela_soto

 

 

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