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

November 14, 2018/2 Comments/by admin Z.9

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.

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

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

November 7, 2018/by Alexander Cole

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

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
Litwin MS. Health related quality of life in older men without prostate cancer. J Urol 1999; 161: 1180–4
Lane A, Metcalfe C, Young GJ et al. Patient‐reported outcomes in the ProtecT randomized trial of clinically localized prostate cancer treatments: study design, and baseline urinary, bowel and sexual function and quality of life. BJU Int 2016; 118: 869–79
Resnick MJ, Barocas DA, Morgans AK et al. The evolution of self‐reported urinary and sexual dysfunction over the last two decades: implications for comparative effectiveness research. Eur Urol 2015; 67: 1019–25
Trinh QD, Cole AP, Dasgupta P. Weighing the evidence from surgical trials. BJU Int 2017; 119: 659–60
Cole AP, Trinh QD. Secondary data analysis: techniques for comparing interventions and their limitations. Curr Opin Urol 2017; 27: 354–9

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

November 7, 2018/by Admin

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.

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

October 24, 2018/by Admin

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.

Guideline of guidelines: primary monotherapies for localised or locally advanced prostate cancer

October 1, 2018/by Admin

Abstract:

Decisions regarding the primary treatment of prostate cancer depend on several patient‐ and disease‐specific factors. Several international guidelines regarding the primary treatment of prostate cancer exist; however, they have not been formally compared. As guidelines often contradict each other, we aimed to systematically compare recommendations regarding the different primary treatment modalities of prostate cancer between guidelines. We searched Medline, the National Guidelines Clearinghouse, the library of the Guidelines International Network, and the websites of major urological associations for prostate cancer treatment guidelines. In total, 14 guidelines from 12 organisations were included in the present article. One of the main discrepancies concerned the definition of ‘localised’ prostate cancer. Localised prostate cancer was defined as cT1–cT3 in most guidelines; however, this disease stage was defined in other guidelines as cT1–cT2, or as any T‐stage as long as there is no lymph node involvement (N0) or metastases (M0). In addition, the risk stratification of localised cancer differed considerably between guidelines. Recommendations regarding radical prostatectomy and hormonal therapy were largely consistent between the guidelines. However, recommendations regarding active surveillance, brachytherapy, and external beam radiotherapy varied, mainly as a result of the inconsistencies in the risk stratification. The differences in year of publication and the methodology (i.e. consensus‐based or evidence‐based) for developing the guidelines might partly explain the differences in recommendations. It can be assumed that the observed variation in international clinical practice regarding the primary treatment of prostate cancer might be partly due to the inconsistent recommendations in different guidelines.

Michelle Lancee, Kari A.O. Tikkinen, Theo M. de Reijke, Vesa V. Kataja, Katja K.H. Aben and Robin W.M. Vernooij

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Article of the week: External validation of the prostascore model in metastatic hormone‐sensitive PCa patients recruited to the CHAARTED study

September 19, 2018/by Admin

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.

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

External validation of the prostascore model in patients with metastatic hormone‐sensitive prostate cancer recruited to the CHAARTED study

Omar Abdel‐Rahman* and Winson Y. Cheung†

*Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt; †Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada

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Abstract

Objective

To externally validate ‘prostascore’ in patients with metastatic hormone‐sensitive prostate cancer recruited to the phase III CHAARTED study.

Methods

We conducted a retrospective analysis of the prospectively collected data from patients with metastatic hormone‐sensitive prostate cancer in the CHAARTED study, a phase III multicentre study conducted between 2006 and 2014. The main outcome of the present analysis was overall survival, assessed using Kaplan–Meier analysis or log‐rank testing, in the whole cohort according to different prostascores. In addition, patients with different scores were compared according to treatment arm.

Fig 1. Kaplan-Meier curves for (A) overall survival according to Prostascore.

Results

A total of 702 cases had complete baseline data, allowing calculation of prostascores and inclusion in the present analysis. Overall survival was assessed according to prostascores in the entire cohort and the P value for overall survival trend was significant (P < 0.001). Likewise, progression‐free survival was assessed according to prostascores in the entire cohort and the P value for progression‐free survival trend was also significant (P < 0.001). Overall survival comparisons according to treatment arm were evaluated among different prostascores. Notably, the P value for overall survival difference was not significant for a prostascore = 2 (P = 0.702), but was significant for scores of 3, 4 and 5 (P < 0.05). The cause‐specific hazard ratio for cancer‐specific survival (adjusted for treatment arm used) was also evaluated. The P value for pairwise comparisons between different scores was significant (P < 0.01) except for the comparison between scores 4 and 5.

Conclusion

The present study further confirms the role of prostascore in predicting the outcomes of patients with metastatic hormone‐sensitive prostate cancer and also highlights its potential role in therapeutic decision‐making.

Editorial: Prognostic and predictive models in hormone-sensitive PCa

September 19, 2018/by Nicholas James

The article by Abdel‐Rahmen and Cheung [1] in the current issue of BJUI takes the Prostascore model [2] developed from epidemiological Surveillance, Epidemiology and End Results (SEER) data and applies it to the prospective randomised trial data from the ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) [3]. This sort of modelling is invaluable, given the inevitable limitations of epidemiological data (retrospective, no data cleaning, key items such as performance status missing, etc.). For models to be useful, they need to be able to discern prognostic categories reliably and with sufficient difference in outcome that they can usefully contribute to clinical decision‐making. They also need to perform better than existing oncological models, such as TNM stage, as outcome predictors. To be truly useful, they also need to identify subgroups of patients who may differentially benefit from different treatments (e.g. human epidermal growth factor receptor 2 [HER2] status in breast cancer therapy with trastuzumab). It is thus important to differentiate prognostic models (which predict outcome but do not help select treatment) from predictive models (which predict outcome and also help select who may benefit from treatment). A common mistake in this setting is to assume that patients with worse outcomes may benefit from more aggressive treatment, whilst those with better outcomes may require less treatment. This is a frequent confounding bias in retrospective data such as SEER. The key test is to look at good‐ and poor‐prognosis patients and examine whether the benefit from (say) chemotherapy is proportionately the same or different in both groups. If the proportional benefit is the same, the model is purely prognostic, if the proportional benefit is different (e.g., a bigger benefit in worse patients), the model is, in addition, predictive. A randomised trial such as CHAARTED is thus ideal for separating these two factors. It is also worth noting that just because a model predicts a relatively better outcome in one subgroup vs another, it does not mean that all patients do not benefit. For example, programmed death 1 (PD‐1) pathway molecule staining is generally prognostic in advanced bladder cancer and partly predictive of better response to PD‐1 pathway drugs such as atezolizumab [4] and pembrolizumab [5], but all patients derive benefit and hence PD‐1 pathway staining is not useful in selecting for treatment.

How does the Prostascore model fare against these various tests? As a prognostic model it clearly separates patients into groups with plausible differences in outcome. However, there exist many systems already that do this and in the clinic, these are probably not useful – it is well understood that men with extensive disease and visceral metastases will do worse than those with less disease – treatment for all will include androgen‐deprivation therapy (ADT). More recently, trial data have emerged showing survival benefit from the first‐line addition of either docetaxel [3, 6] or abiraterone [7, 8] to ADT. There is controversy about whether this benefit is confined to men with high‐volume disease as claimed by some [9], or applies more generally, as per Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE) [6] and the Systemic Treatment Options for Cancer of the Prostate (STOpCaP) meta‐analysis [10]. Can Prostascore help to resolve this problem? Sadly the answer is no. The analysis presented here [1] does not offer convincing evidence of a useful predictive value with respect to selection for first‐line docetaxel. Firstly, the sample size is small (702 men), with only 118 in the lowest risk category (who of course also have the lowest event rate, hence proportionately even less power). In the higher‐risk categories, there seems to be clear evidence of benefit from docetaxel (larger numbers of men and higher event rates). No pooled analysis is presented, but it seems likely that this would show a benefit from docetaxel in the whole sample set, exactly as reported in CHAARTED [3]. Data from underpowered, post hoc, subgroup analysis should not be over‐interpreted [11].

How should we move forward from here? The STAMPEDE group will be presenting data from both the docetaxel and abiraterone parts of the study, classified both by the high‐/low‐volume split in CHAARTED [3] and the high‐/low‐risk split in the LATITUDE trial (multinational, randomised placebo‐controlled phase III clinical trial of men with newly diagnosed, high‐risk metastatic prostate cancer who had not previously received ADT. All patients had at least two of three risk factors: Gleason score of ≥8, ≥3 bone metastases, or ≥3 visceral metastases) [7]. If evidence of a differential response to these agents by these prognostic tools exists, it may be worth applying the Prostascore tool to the STAMPEDE dataset. If there is no evidence of these existing prognostic classifiers also being predictive of best therapy choice, there is probably only a limited role for Prostascore as a prognostic tool in an already crowded space. risk factors and risk of developing cancer.

Nicholas D. James

Institute of Cancer and Genomic Sciences, University of Birmingham,
Queen Elizabeth Hospital, Birmingham, UK

References

Abdel‐Rahman O, Cheung WY. External validation of the prostascore model in patients with metastatic hormone‐sensitive prostate cancer recruited to the CHAARTED study. BJU Int 2018; 122: 394–400
Abdel‐Rahman O. Prostascore: a simplified tool for predicting outcomes among patients with treatment‐naive advanced prostate cancer. Clin Oncol (R Coll Radiol) 2017; 29: 732–8
Sweeney CJ, Chen YH, Carducci M et al. Chemohormonal therapy in metastatic hormone‐sensitive prostate cancer. N Engl J Med 2015; 373: 737–46
Balar AV, Galsky MD, Rosenberg JE et al. Atezolizumab as first‐line treatment in cisplatin‐ineligible patients with locally advanced and metastatic urothelial carcinoma: a single‐arm, multicentre, phase 2 trial. Lancet 2017; 389: 67–76
Bellmunt J, de Wit R, Vaughn DJ et al. Pembrolizumab as second‐line therapy for advanced urothelial carcinoma. N Engl J Med 2017; 376: 1015–26
James ND, Sydes MR, Clarke NW et al. Addition of docetaxel, zoledronic acid, or both to first‐line long‐term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet 2016; 387: 1163–77
Fizazi K, Tran N, Fein L et al. Abiraterone plus prednisone in metastatic, castration‐sensitive prostate cancer. N Engl J Med 2017; 377: 352–60
James ND, de Bono JS, Spears MR et al. Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med 2017; 377: 338–51
Gravis G, Boher JM, Chen YH et al. Burden of metastatic castrate naive prostate cancer patients, to identify men more likely to benefit from early docetaxel: further analyses of CHAARTED and GETUG‐AFU15 Studies. Eur Urol 2018; 73: 847–55
10 Vale CL, Burdett S, Rydzewska LH et al. Addition of docetaxel or bisphosphonates to standard of care in men with localised or metastatic, hormone‐sensitive prostate cancer: a systematic review and meta‐analyses of aggregate data. Lancet Oncol 2016; 17: 243–56
Spears MR, James ND, Sydes MR. ‘Thursday’s child has far to go’ – interpreting subgroups and the STAMPEDE trial. Ann Oncol 2017; 28: 2327–30

Article of the Week: Analysis of hydrogel spacer for PCa RT

September 5, 2018/by admin Z.9

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video discussing the paper.

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

Prospective analysis of hydrogel spacer for patients with prostate cancer undergoing radiotherapy

Michael Chao*†, Huong Ho† , Yee Chan*‡, Alwin Tan§, Trung Pham¶, Damien Bolton*‡, Andrew Troy*, Catherine Temelcos**, Shomik Sengupta*†† , Kevin McMillan‡, Chee Wee Cham§, Madalena Liu‡, Wei Ding†, Brindha Subramanian†, Jason Wasiak*‡‡, Daryl Lim Joon*†, Sandra Spencer† and Nathan Lawrentschuk*

*The Austin Hospital, Heidelberg, Vic., Australia, †Genesis Cancer Care Victoria, Ringwood East, Vic., Australia, ‡Ringwood Private Hospital, Ringwood East, Vic., Australia, §The Bays Hospital, Mornington, Vic., Australia, ¶ The Valley Private Hospital, Mulgrave, Vic., Australia, **St Vincent’s Hospital, Fitzroy, Vic., Australia, ††Melbourne University; Eastern Health Clinical School, Monash University, Clayton, Vic., Australia, and ‡‡University of Melbourne, Melbourne, Vic., Australia

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Abstract

Objective

To report on the dosimetric benefits and late toxicity outcomes after injection of hydrogel spacer (HS) between the prostate and rectum for patients treated with prostate radiotherapy (RT).

Patients and Methods

In all, 76 patients with a clinical stage of T1–T3a prostate cancer underwent general anaesthesia for fiducial marker insertion plus injection of the HS into the perirectal space before intensity‐modulated RT (IMRT) or volumetric‐modulated arc RT (VMAT). HS safety, dosimetric benefits, and the immediate‐ to long‐term effects of gastrointestinal (GI) toxicity were assessed.

Results

There were no postoperative complications reported. The mean (range) prostate size was 66.0 (25.0–187.0) mm. Rectal dose volume parameters were observed and the volume of rectum receiving 70 Gy (rV₇₀), 75 Gy (rV₇₅) and 78 Gy (rV₇₈) was 7.8%, 3.6% and 0.4%, respectively. In all, 21% of patients (16/76) developed acute Grade 1 GI toxicities, but all were resolved completely by 3 months after treatment; whilst, 3% of patients (2/76) developed late Grade 1 GI toxicities. No patients had acute or late Grade ≥2 GI toxicities.

Conclusion

Injection of HS resulted in a reduction of irradiated rectal dose volumes along with minimal GI toxicities, irrespective of prostate size.

Editorial: 2018 – A Spacer Odyssey

September 5, 2018/by Simon Hughes

The optimisation of radical external-beam radiotherapy treatment is ultimately a compromise. The aim is to deliver a clinically effective radiation dose to the tumour target, whilst limiting the irradiation of surrounding normal tissue to minimise acute and late side effects. Modern image-guided intensity-modulated radiotherapy (IG-IMRT) allows very accurate treatment delivery, which improves this therapeutic ratio. However, there are limitations in its ability to reduce toxicity, due to the constraints of regional anatomy and the physical properties of photon beams. A variety of additional organ-specific techniques exist to further minimise the impact of radiotherapy on adjacent healthy tissue. These range in complexity from ovarian auto-transplantation in selected patients awaiting pelvic radiotherapy for gynaecological malignancies, to delivering radiotherapy for left-sided breast cancers at inspiratory breath-hold to maximise the distance of the chest wall from the left anterior descending coronary artery.

For prostate cancer radiotherapy, the normal structures that determine the optimal safely deliverable dose include the rectum (anterior rectal wall), bladder, femoral heads and penile bulb. IG-IMRT has facilitated dose-escalation, and the treatment of patients previously considered to be ineligible for a radical treatment; both with acceptable toxicity. Higher doses result in improved prostate-cancer biochemical (PSA) control rates, and metastasisfree survival, but as yet no overall survival benefit has been demonstrated in individual trials, despite 10-year follow-up [1]. This may due to the long natural history of localised prostate cancer, the impact of competing comorbidities [2], and the ever-increasing efficacy of treatments for metastatic disease on relapse.

Rectal spacers are a further refinement to the delivery of radical IG-IMRT to the prostate gland. By inserting a biodegradable substance / inflatable biodegradable balloon into the anterior perirectal space, the distance between the prostate and the anterior rectal wall can be increased by approximately 1cm. This reduces the volume of rectum lying within the high-dose radiation field, thereby reducing late bowel toxicity. A recently reported randomised Phase III trial found a reduction the 3-year incidence of ≥ Grade 1 and ≥ Grade 2 rectal toxicity (9.2% v 2.0%; p=0.28; and 5.7% v 0%; p=0.12 respectively) with the addition of a rectal spacer [3]. This was in a very select group of patients: PSA ≤20, cT1-2, International Society of Urological Pathology (ISUP) Prostate Cancer Grade 1-3 (<50% of cores involved), prostate volume <80cc, no use of androgen deprivation therapy, and the use of MRI-CT fusion to aid prostate delineation during the planning process.

In this issue of the BJUI, Chao et al. [4] report their prospective single-centre experience of using a rectal spacer device. This is not a randomised study, and no control arm exists to assist in quantifying the clinical impact of inserting a spacer. However, the patient population studied closely reflects that undergoing radical radiotherapy in most oncology departments world-wide. There were no limitations placed on prostate size (45% were 50- 100cc; 17% >100cc; maximum 187cc), PSA (10% had a PSA >20; maximum 117), or ISUP histological grade (27% were Grade 4 and 5); and 27% of patients were cT3a on imaging. They demonstrated that spacer insertion was safe across a diverse population of men with localised prostate cancer. Further, acceptable prostate-rectal wall separation and rectal dosimetry could be achieved irrespective of prostate size – which was reflected by the low rates of cumulative late rectal toxicity when assessed at a median follow-up of 14 months.

As with any new technique, additional clarification is required to determine exactly where rectal spacers fit into the radiotherapy armoury. In the study by Chao et. al. the Radiation Oncologists did not have access to CT-MRI fusion at the planning stage. As the electron densities for the prostate, rectal-spacer and rectal wall are similar, it can be challenging to determine the anatomical boundaries on CT alone. However, if growing clinical experience now permits accurate delineation by merely adjusting the window levels on the Planning CT, this could facilitate more widespread introduction of the technique, outside the specialist centres with MR-fusion capabilities.

Patient selection is also key to the introduction of this technique. Patient series have reported the safety of the spacer insertion technique across a range of prostate sizes, and prostate cancer risk groups. However, prospective randomised data is lacking on whether treatment efficacy is affected by using a spacer in high-risk / locally advanced disease – the population most likely to benefit from dose-escalated radical radiotherapy [5]. Further, in the only randomised study to date, >90% of patients in the control arm experienced no late rectal toxicity, and >94% experienced no ≥Grade 2 rectal toxicity. Based on long-term follow-up data from the RT01 study, this was an appropriate time-point at which to assess late bowel toxicity, which peaks at 12-36 months before declining [6]. Therefore, the majority of patients do not experience clinically significant late toxicity even without a spacer.

Rectal spacers have the potential to make a valuable contribution to radical IG-IMRT treatment for localised prostate cancer. However, predictive factors are required to identify which patients are likely to benefit from the technique. For many patients, with access to the latest radiotherapy planning and delivery systems, spacers may represent an additional costly procedure with limited benefit.

S.R.Hughes
Oncology Department, Guy’s & St. Thomas’ NHS Trust, London, UK

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References

1. Dearnaley DP, Jovic G, Syndikus I, et. al. The Lancet Oncol. 2014; 15(4): 464-473

2. Lu-Yao GL, Albertsen PC, Moore DF, Lin Y, DiPaola RS, Yao SL. Fifteen-year outcomes following conservative management among men aged 65 years or older with localised prostate cancer. Eur Urol. 2015; 68(5): 805-11

3. Hamstra DA, Mariados N, Sylvester J et. al. Continued Benefit to Rectal Separation for Prostate Radiation Therapy: Final Results of a Phase III Trial. Int J Radiat Oncol Biol Phys 2017; 97(5): 976-985

4. Chao M, Ho H, Chan Y et. al. Prospective Analysis of Hydrogel Spacer for Prostate Cancer Patients Undergoing Radiotherapy. BJUI 2018

5. Kalbasi A, Li J, Berman AT. Dose-Escalated Irradiation and Overall Survival in Men with Non-metastatic Prostate Cancer. JAMA Oncol. 2015; 1(7): 897-906

6. Syndikus I, Morgan RC, Sydes MR, Graham JD, Dearnaley DP. Late Gastrointestinal Toxicity After Dose-Escalated Conformal Radiotherapy For Early Prostate Cancer:

Video: Hydrogel spacer for PCa RT

September 5, 2018/by admin Z.9

Prospective analysis of hydrogel spacer for patients with prostate cancer undergoing radiotherapy

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Abstract

Objective

To report on the dosimetric benefits and late toxicity outcomes after injection of hydrogel spacer (HS) between the prostate and rectum for patients treated with prostate radiotherapy (RT).

Patients and Methods

Results

Conclusion

Injection of HS resulted in a reduction of irradiated rectal dose volumes along with minimal GI toxicities, irrespective of prostate size.

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