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

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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.). 2014; 348: 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 intent. Eur Urol 2017; 71: 618–29

 

Editorial: Contemporary quality‐of‐life scores provide a key foundation for high‐quality cancer research

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Prostate cancer is the most common male malignancy in many countries, including the UK/Northern Ireland. Given excellent oncological outcomes for appropriately treated localised cancer, there is an increasing focus on understanding the quality‐of‐life implications of different treatment options.

As Donnelly et al. [1] emphasise, contemporary cohorts of untreated men can provide useful comparisons for inferring the impact of treatment. Specifically, updated population‐level observations of urinary, bowel, and sexual dysfunction are needed to provide a baseline for such discussions. Surveys should focus on particular populations (e.g. geographic), utilise prostate cancer‐specific questionnaires, and ensure age‐matched cohorts. Such baseline characteristics are essential to teasing apart the impact of prostate cancer and its treatment from ageing and comorbidities.

Donnelly et al. [1] sampled 10 000 men in Northern Ireland aged >40 years, using the EuroQoL five Dimensions five Levels (EQ‐5D‐5L) survey to assess a general health baseline and Extended Prostate Cancer Composite (EPIC) questionnaire to determine bladder, bowel, and sexual function more specifically. In all, 2 955 men responded, although ultimately only men aged >60 years were analysed to better match the age distribution of patients with prostate cancer. Strikingly, they found that nearly two out of five men reported at least one urinary, bowel, or sexual issue. A third of men reported some degree of urinary leakage, 26% had some degree of bowel problems, and as much as 57.9% of respondents had some problem with sexual function [1].

Nearly two decades ago, Litwin [2] published a health‐related quality of life control sample of older men in the USA without prostate cancer using the University of California Los Angeles Prostate Cancer Index (UCLA‐PCI, a precursor to EPIC). He found ageing subjects had diminished urinary continence, bowel function, and sexual potency, with similar rates to the Northern Ireland study: a third reported urinary leakage, a third had bowel complaints, and nearly two‐thirds claimed to have erectile dysfunction (ED).

In contrast, patient‐reported outcomes in the Prostate Testing for Cancer and Treatment (ProtecT) trial showed low levels of urinary incontinence and bowel symptoms, and one‐third of men had sexual dysfunction [3]. The difference here in ED when compared to Donnelly et al. [1] may be attributed to the age distribution differences between the cohorts, as ProtecT included men aged 50–69 years and the Northern Ireland group looked only at men aged >60 years. This highlights the importance of ensuring age‐matched cohorts when using population‐based surveys as baselines for assessment counselling.

Furthermore, Resnick et al. [4] evaluated the change in patient‐reported urinary incontinence and ED over time in two cohorts of patients enrolled almost 20 years apart. They compared patients enrolled in 1994–1995 in the Prostate Cancer Outcomes Study (PCOS) vs those enrolled in 2011–2012 in the Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study. Men in PCOS were surveyed using UCLA‐PCI, and those in CEASAR completed EPIC‐26. They found that self‐reported urinary incontinence was more common in CEASAR than in PCOS (7.7% vs 4.7%), as was ED (44.7% vs 24%). These differences could be due to rising rates of comorbidities associated with ED and urinary incontinence or they may reflect an increase in social awareness and disclosure of these issues.

Taken together, these self‐reported rates of pretreatment urinary and sexual function underscore the potential for significant variation in reporting of patient quality‐of‐life outcomes in prostate cancer.

This does not mean that patient‐reported outcomes should be ignored. Rather the takeaway is that we must invest in tools to ensure that reporting is appropriate, standardised, and accurate [5]. And regardless of whether these data are collected prospectively, or retrospectively, it is vital to use appropriate statistical methods and scientific principles to account for bias and to ensure that causal inferences are valid [6].

As prostate cancer survival and mortality rates improve, patients and clinicians must weigh treatment‐specific short‐ and long‐term effects on quality of life. Patient‐reported outcome measures are vital to assessing these major impacts. Contemporary, population‐based cohorts such as that provided by Donnelly et al. [1], provide a key tool for better interpreting and understanding these results.

References

  1. Donnelly DW, Donnelly C, Kearney T et al. Urinary, bowel and sexual health in older men from Northern Ireland. BJU Int 2018; 122: 845–57
  2. Litwin MS. Health related quality of life in older men without prostate cancer. J Urol 1999; 161: 1180–4

 

 

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

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

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

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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. Prevent most unhealthy conditions after reading these biofit reviews.

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.

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Video: Urinary, bowel and sexual health in older men

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

Read the full article

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. Prevent most unhealthy conditions with carbofix.

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. Check out the latest gluconite reviews.

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.

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

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

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

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

 

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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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Editorial: Close surgical margins after RP: how to make a complex story even more complex

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Surgical margin (SM) status after radical prostatectomy (RP) for clinically localized prostate cancer (PCa) is a measure of surgical quality and retains some prognostic value. Positive SMs (PSMs) have long been considered an adverse oncological outcome because they were repeatedly found to be associated with a higher risk of biochemical recurrence (BCR), and are still among the factors guiding the decision to deliver adjuvant treatments; however, the long‐term impact of PSMs on survival remains uncertain because it is largely affected by other concurrent risk modifiers [1,2,3].

The clinical significance of so‐called close SMs (CSMs), that is, negative SMs (NSMs) with tumour foci approaching, but not involving, the inked cut surface of the RP specimen, is a far less investigated field of research, with contradictory findings in the few available studies (Table 1 [4–12]). Some studies showed a significant association with risk of disease progression (mainly measured with BCR), while others did not.

 

The study by Herforth et al. [12] published in this issue of BJUI further adds to the debate on CSMs, with an analysis of the largest series reported to date. The authors assessed the impact of CSMs vs NSMs vs PSMs after RP on BCR, PCa‐specific and overall survival in ~4 300 men included in the Shared Equal Access Regional Cancer Hospital cohort. CSMs were defined as cancer foci within 1 mm from the inked specimen surface, and were found in 372 patients (9%). The median follow‐up was 6.5 years. On multivariable analysis accounting for several established prognostic factors, CSMs were significantly associated with a higher BCR risk compared with NSMs, but a lower risk compared with PSMs. Notably, SM status alone did not influence PCa‐specific or overall survival. Major limitations to this retrospective analysis were lack of central pathology review and inadequate follow‐up length to assess survival.

The main question yet to answer is whether CSMs entail a biological entity that is distinct from both negative (but not close) SMs and PSMs. Advances in this area cannot be made without taking into consideration the knowledge of PSMs that has accumulated over the past years. We suggest, therefore, that the following principles be adhered to in order to ascertain the true significance of CSMs.

    1. Uniform definition
      Some of the available studies used an arbitrary threshold (0.1 or 1 mm) to designate CSMs, but distance between tumour and SMs should be ideally evaluated as a continuous variable before attempting to categorize it.
    2. Accurate pathology examination
      It has been hypothesized that CSMs could be the expression of occult PSMs that are present in different close planes of resection missed by standard sectioning as a result of block sampling bias 11. Encountering CSMs should, then, probably prompt further specimen processing that requires standardization.
    3. Correct prognostic assessment
      It is now accepted that PSMs per se are not sufficient to confer a dismal prognosis, rather it is the concomitant effect of other pathological risk factors (such as stage, tumour volume, Gleason score at SMs, location and extent of PSMs) that determines the aggressive tumour behaviour. The same could apply to CSMs; therefore, their prognostic effect should be investigated by adding ‘interaction terms’ to classic multivariable models that account for a putative synergistic biological effect. It might well be, in fact, that the simultaneous presence of CSMs and extracapsular disease (or higher Gleason score, greater tumour volume, perineural/lymphovascular invasion) results in a final risk of detrimental outcome exceeding the additive combination of the individual risks.
    4. Adequate follow‐up
      At least a decade is required to appropriately test the association of CSMs in patients undergoing RP with endpoints of meaningful interest.

The truth about SMs after RP is still hard to reach, and the issue of CSMs possibly complicates this scenario. While we await further characterization of PCa facilitated by advances in genetic profiling, we recommend that future clinical research in the field does not run into the methodological obstacles of the past.

Gianluca Giannarini, Alessandro Crestani and Claudio Valotto

Urology Unit, Academic Medical Centre ‘Santa Maria della Misericordia’, Udine, Italy

 

References

  1. Yossepowitch O, Bjartell A, Eastham JA et al. Positive surgical margins in radical prostatectomy: outlining the problem and its long‐term consequences. Eur Urol 2009; 55: 87–99
  2. Yossepowitch O, Briganti A, Eastham JA et al. Positive surgical margins after radical prostatectomy: a systematic review and contemporary update. Eur Urol 2014; 65: 303–13
  3. Stephenson AJ, Eggener SE, Hernandez AV et al. Do margins matter? The influence of positive surgical margins on prostate cancer‐specific mortality. Eur Urol 2014; 65: 675–80
  4. Epstein JI, Sauvageot J. Do close but negative margins in radical prostatectomy specimens increase the risk of postoperative progression? J Urol 1997; 157: 241–3
  5. Emerson RE, Koch MO, Daggy JK, Cheng L. Closest distance between tumor and resection margin in radical prostatectomy specimens: lack of prognostic significance. Am J Surg Pathol 2005; 29: 225–9
  6. Bong GW, Ritenour CW, Osunkoya AO, Smith MT, Keane TE. Evaluation of modern pathological criteria for positive margins in radical prostatectomy specimens and their use for predicting biochemical recurrence. BJU Int 2009; 103: 327–31 
  7. Lu J, Wirth GJ, Wu S et al. A close surgical margin after radical prostatectomy is an independent predictor of recurrence. J Urol 2012; 188: 91–7
  8. Izard JP, True LD, May P et al. Prostate cancer that is within 0.1 mm of the surgical margin of a radical prostatectomy predicts greater likelihood of recurrence. Am J Surg Pathol 2014; 38: 333–8
  9. Whalen MJ, Shapiro EY, Rothberg MB et al. Close surgical margins after radical prostatectomy mimic biochemical recurrence rates of positive margins. Urol Oncol 2015;33:494.e9–14
  10. Gupta R, O’Connell R, Haynes AM et al. Extraprostatic extension (EPE) of prostatic carcinoma: is its proximity to the surgical margin or Gleason score important? BJU Int 2015; 116: 343–50
  11. Paluru S, Epstein JI. Does the distance between tumor and margin in radical prostatectomy specimens correlate with prognosis: relation to tumor location. Hum Pathol 2016; 56: 11–15 Erratum in: Hum Pathol 2017; 60: 212
  12. Herforth C, Stroup SP, Chen Z et al. Radical prostatectomy and the effect of close surgical margins: results from the SEARCH database. BJU Int 2018; 122: 592–8

 

Video: Shortcomings in the management of undescended testis

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Shortcomings in the management of undescended testis: guideline intention vs reality and the underlying causes – insights from the biggest German cohort

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Abstract

Objectives

To assess the implementation of the current guideline and identify potential underlying causes for late surgery in children with undescended testis (UDT) in Germany. UDT is the most common surgical issue in paediatric urology and to avoid malignant degeneration and subfertility current guidelines recommend orchidopexy during the first year of life; however, this seems not to be implemented in practice.

Patients and Methods

In all, 5 547 patients with cryptorchidism at 16 hospitals nationwide were studied regarding age at orchidopexy between 2003 and 2016. Multivariate analysis was performed to identify factors influencing timing of surgery. Additionally, a survey on knowledge of UDT management was conducted amongst physicians treating boys and final‐year medical students.

Results

Between 2003 and 2008 only 4% of boys with UDT underwent surgery before the age of 1 year. After the guideline update from 2009, this figure was 5% from 2010 to 2012, and 8% from 2013 to 2016. The presence of a specialised department for paediatric surgery, as well as a high UDT case‐to‐year ratio positively influenced the timing of orchidopexy. The survey revealed discipline‐specific differences in the levels of knowledge about UDT management. One‐third of respondents did not know the guideline recommendations and 61% felt insufficiently informed. International comparisons revealed significant differences in the age at surgery of boys with UDT, with Germany and Great Britain ranging in the middle of the field.

Conclusion

Currently, only a small proportion of boys with UDT are operated upon during their first year of life. The level of knowledge in attending physicians remains in need of improvement. This should be actively addressed, i.e. by campaigns and educational programmes. Further studies are needed to investigate the underlying causes of late orchidopexy in UDT.

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Article of the week: Testicular asymmetry in healthy adolescent boys

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

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation. The authors have also supplied a video to accompany the article. Prevent most unhealthy conditions with exercise, follow this guide if you are willing to stay fit after 50.

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

Testicular asymmetry in healthy adolescent boys

Donald Vaganee*† , Frederik Daems*, William Aerts*, Rosina Dewaide*, Tinne van den Keybus*, Karen De Baets†, Stefan De Wachter*† and Gunter De Win*†

*Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp and †Department of Urology, Antwerp University Hospital, Edegem, Belgium

 

 
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Abstract

Objectives

To assess the presence of testicular asymmetry and the currently used threshold values in varicocoele management in a healthy adolescent population. Stay healthy with Biofit probiotics.

Subjects and Methods

We conducted an observational cross‐sectional study from April 2015 until December 2016 in which we recruited 539 adolescent boys aged 11–16 years. A clinical examination including testicular size measurement by ultrasonography was performed. Testicular volume (TV) was calculated using the Lambert formula (length × width × height × 0.71). The Testicular Atrophy Index (TAI) was calculated using the formula [(TV right – TV left)/largest TV] × 100. The data for all statistical analyses were stratified for Tanner stage for genital development (TSG) and pubic hair (TSP). Non‐parametric tests were used to assess the difference between right and left TV, and the prevalence of a smaller left testis for the entire population, and between each TSG and TSP. Parametric tests were used to determine the difference in mean TAI between each TSG and TSP, and to compare the mean TAI to a test value of 0.

Results

Of the 539 recruited boys, we excluded 194 due to a current or past pathology, including varicocoeles, influencing normal (testicular) growth or due to incomplete data. Most boys were in the second Tanner stage, followed by the third Tanner stage. The mean (sd) age of the entire population was 13.33 (1.25) years. Of the 345 included participants the mean (sd) left TV was 7.67 (5.63) mL and right TV was 7.97 (5.90) mL. The mean (sd) TAI was 2.85 (17.00)%. In all, 203 (58.84%) boys had a smaller left testis and 142 (41.16%) had a smaller right testis. In all, 51 boys (14.78%) had a TAI >20%, 45 (13.04%) had a TV difference (TVD) of >2 mL with a deficit in left TV, and 69 (20.00)% had a TAI >20% or a TVD of >2 mL with a deficit in left TV. Related‐samples Wilcoxon signed‐rank test showed a significant difference in mean left and right TV for the entire population, and more specifically for TSG3 (P < 0.001) and TSP3 (P = 0.004). A one‐sample t‐test showed a significant difference in the mean TAI vs the test value of 0 for the entire population (P = 0.002), and more specifically for TSG3 (P < 0.001) and TSP3 (P = 0.003).

Conclusion

Testicular asymmetry, with a smaller left testis, was seen in a considerable number of healthy adolescents. One out of five adolescents had a smaller left testis and met one of the threshold values currently used in varicocoele management. Therefore, in left‐sided unilateral inguinoscrotal pathology, a smaller ipsilateral testis in combination with a TAI of >20% and/or TVD of >2 mL requires careful interpretation and serial measurements of TV should always be performed. Furthermore, this study provides reference values for TV, TVD and TAI according to TSG and TSP for a healthy adolescent population.

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Editorial: Measuring testicular asymmetry in healthy adolescent boys

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The Antwerp group has provided major contributions in the field of the adolescent varicocoele before [1], leveraging their long follow‐up and school‐based screening. Here, the focus is on ultrasound measures of testis volume and the natural variation in testis size detected in healthy boys without varicocoele [2].

The cohort is a mix of secondary school evaluations and those recruited at a tertiary hospital. Hospital‐recruited subjects would be concerning for this study design, but fortunately the prevalence of medical conditions in this cohort mirrors that of other population‐based investigations (16.3% clinical varicocoele, 3.5% cryptorchidism). This reassures the reader that the results seen here are generalizable, with the caveat that it is nearly 85% Caucasian. Further favouring generalisability, we calculate the mean body mass index of the cohort at approximately the 58th percentile by Center for Disease Control and Prevention tables.

In total, 13% of screened boys had a left testis 2 mL smaller than the right, a fact made more pronounced by the younger skew of the cohort – given the known variance in ultrasound measurement it would be more likely to detect such a difference with larger volumes. With larger measures, a small linear underestimate is more likely to trigger the 2 mL volume difference as a function of geometry. The authors assert that the testicular atrophy index is normally distributed. In the narrowest sense this is unlikely to be true, as the test statistics required (e.g. Shapiro–Wilk) are not shown and are quite strict. Nevertheless, the spirit of this claim stands as without a doubt there is a ‘curve’, and readers expected to find perfect symmetry in the ultrasound‐measured gonadal size of healthy boys will be disappointed.

The authors have advanced yet another measurement of testicular asymmetry, modifying the existing testicular atrophy index, and this is difficult to support. The field is already crowded with an alphabet soup of such measures, and this new one is not algebraically equivalent to those extant [3]. It would serve us all well to agree upon a standard.

There are implications from this research on practice. The European Association of Urology (EAU) guidelines state that urologists should ‘perform surgery for […] varicocele associated with a small testis (size difference of >2 mL or 20%)’ at level of evidence 2 and grade of recommendation B [4]. In the absence of comment on persistence or longitudinal follow‐up, this is a position that both we and the authors oppose. We favour longitudinal measurements and a semen analysis, should the boys reach Tanner V status. The authors take this a step further and suggest that volume differential calculations should be used with ‘great caution’. Here we differ from the authors in opinion; difference in testis volume, especially in extremes, does appear to be associated with low total motile sperm counts, and we believe that such measures have their place [5,6].

The primary implication of this paper [2] is that differential in testis volume is common and benign. The reader should be cautioned that the latter has not been proven as the control boys have not produced semen samples or demonstrated paternity. We know only that the studied boys are presumed healthy, not fertile. There are additional limitations, largely noted by the authors. This is a cross‐sectional study, and it would be interesting to see if the volume differences are transient or persistent, as they could be present due to measurement artefact or a natural difference in growth. The growth curves by boxplot are useful, but perhaps less so than formal growth chart with percentiles (which require sophisticated techniques to generate [7]). This work also serves as a reminder that in clinical classification of adolescent development, recording Tanner stage by both genital and hair development is most rigorous.

We join the authors in cautioning against using a single volume‐based data point, such as a fixed or proportional difference in testis volumes, as a decision for surgery.

 

Michael P. Kurtz and David A. Diamond

Boston Children’s Hospital, Boston, MA, USA

 

References

  1. Bogaert G, Orye C, De Win G. Pubertal screening and treatment for varicocele do not improve chance of paternity as adult. J Urol 2013; 189: 2298–303
  2. Vaganée D, Daems F, Aerts W et al. Testicular asymmetry in healthy adolescent boys. BJU Int 2018; 122: 654–66
  3. Christman MS, Zderic SA, Kolon TF. Comparison of testicular volume differential calculations in adolescents with varicoceles. J Pediatr Urol 2014; 10: 396–8
  4. European Association of Urology. European Association of Urology Guidelines, 2015 Edition. Available at: https://uroweb.org/wp-content/uploads/EAU-Extended-Guidelines-2015-Edn.pdf. Accessed May 2018
  5. Keene DJ, Sajad Y, Rakoczy G, Cervellione RM. Testicular volume and semen parameters in patients aged 12 to 17 years with idiopathic varicocele. J Pediatr Surg 2012; 47: 383–5
  6. Kurtz MP, Zurakowski D, Rosoklija I et al. Semen parameters in adolescents with varicocele: association with testis volume differential and total testis volume. J Urol 2015; 193(Suppl.): 1843–7
  7. Department of Health and Human Services, Center for Disease Control and Prevention, National Center for Health Statistics. 2000 CDC Growth Charts for the United States: Methods and Development. Series 11, Number 246. Available at: https://www.cdc.gov/nchs/data/series/sr_11/sr11_246.pdf. Accessed May 2018

Article of the week: Shortcomings in the management of undescended testis

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

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

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

Shortcomings in the management of undescended testis: guideline intention vs reality and the underlying causes – insights from the biggest German cohort

Philip Boehme*†, Berit Geis‡, Johannes Doerner§, Stefan Wirth* and Kai O. Hensel*

*Witten/Herdecke University, Department of Paediatrics, Centre for Clinical and Translational Research, Wuppertal University Hospital, Wuppertal, Germany; †Cardiovascular Research, Bayer Pharma AG, Wuppertal, Germany; ‡Institute of Medical Biometry and Epidemiology, Faculty of Health, Witten/Herdecke University, Witten, Germany; and §Witten/Herdecke University, Department of Surgery, Centre for General and Visceral Surgery, HELIOS University Hospital Wuppertal, Wuppertal, Germany

 
Read the full article

Abstract

Objectives

To assess the implementation of the current guideline and identify potential underlying causes for late surgery in children with undescended testis (UDT) in Germany. UDT is the most common surgical issue in paediatric urology and to avoid malignant degeneration and subfertility current guidelines recommend orchidopexy during the first year of life; however, this seems not to be implemented in practice.

Patients and Methods

In all, 5 547 patients with cryptorchidism at 16 hospitals nationwide were studied regarding age at orchidopexy between 2003 and 2016. Multivariate analysis was performed to identify factors influencing timing of surgery. Additionally, a survey on knowledge of UDT management was conducted amongst physicians treating boys and final‐year medical students.

 

Results

Between 2003 and 2008 only 4% of boys with UDT underwent surgery before the age of 1 year. After the guideline update from 2009, this figure was 5% from 2010 to 2012, and 8% from 2013 to 2016. The presence of a specialised department for paediatric surgery, as well as a high UDT case‐to‐year ratio positively influenced the timing of orchidopexy. The survey revealed discipline‐specific differences in the levels of knowledge about UDT management. One‐third of respondents did not know the guideline recommendations and 61% felt insufficiently informed. International comparisons revealed significant differences in the age at surgery of boys with UDT, with Germany and Great Britain ranging in the middle of the field.

Conclusions

Currently, only a small proportion of boys with UDT are operated upon during their first year of life. The level of knowledge in attending physicians remains in need of improvement. This should be actively addressed, i.e. by campaigns and educational programmes. Further studies are needed to investigate the underlying causes of late orchidopexy in UDT.

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