Tag Archive for: radiotherapy

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RE: Opportunity of widening the resort to multiparametric MRI/transrectal ultrasound fusion imaging-guided prostate cancer brachytherapy

Sir,

Thank you for your interest in our article regarding whole-gland brachytherapy to the prostate for prostate cancer (1). Your letter is highlighting the expanding role of brachytherapy to that of focal therapy (2). We agree that multiparametric magnetic resonance imaging (mpMRI) scans have expanded the ability to localise tumours and indeed that they may be useful in carefully selected men wishing to undergo focal therapy. However, other  advances such as the use of fiducial markers and spacers have also allowed better dosimetry and for a reduction in side effects (3).  The safety and performance of brachytherapy in whole gland treatment means we should have faith in it as a modality to destroy cancer on the focal therapy setting. There are new trials being developed with focal brachytherapy and we look forward to the results in the coming years.

 

References

  1. Chao MW, Grimm P, Yaxley J, Jagavkar R, Ng M, Lawrentschuk N. Brachytherapy: state-of-the-art radiotherapy in prostate cancer. BJU Int  2015; 116(S3): 80-8. doi: 10.1111/bju.13252.
  1. Nguyen PL, Trachtenberg J, Polascik TJ. The role of focal therapy in the management of localised prostate cancer: a systematic review. Eur Urol. 2014 Oct;66(4):732-51. doi: 10.1016/j.eururo.2013.05.048. Epub 2013 Jun 6. Review.
  1. Ng M1, Brown E, Williams A, Chao M, Lawrentschuk N, Chee R. BJU Int. 2014 Mar;113 Suppl 2:13-20. doi: 10.1111/bju.12624. Fiducial markers and spacers in prostate radiotherapy: current applications.

 

 

Letter to the Editor

Opportunity of widening the resort to multiparametric MRI/transrectal ultrasound fusion imaging-guided prostate cancer brachytherapy  

Sir,

I have recently read, with high interest, the review article “Brachytherapy: state-of-the-art radiotherapy in prostate cancer”, by Chao et al.[1].  The authors made extremely clear the advanced technologies of computerized treatment planning and imaging-guided delivery modalities to reach a tailored ablative prostate tumor target dose by resorting to either low-dose-rate (LDR) or high-dose-rate (HDR) different brachytherapy procedures as regards three basic – low, intermediate, high – disease risk classificative conditions.   

It is today proven that focal instrumental procedures inside the prostate gland – from biopsy to various prostate cancer focused ablative strategies, among which laser interstitial thermal therapy and particularly the prostate cancer brachytherapy – might require the resort to proper software digital overlay-mediated fusion of both beforehand multiparametric magnetic resonance imaging (mpMRI) scans and later real-time transrectal 3D ultrasound findings.  Like this, indeed, intriguing developments  in software modelling techniques have led to reach, by a mpMRI-ultrasound image fusion approach, more accurate targeted prostate cancer biopsies than those by transrectal ultrasound imaging alone achieved [2,3].

If the transperineal focal laser prostate tumor ablation  usually occurs only with the guidance of mpMRI (T2-weighted, diffusion-weighted, dynamic contrast material) [4], as regards the prostate cancer brachytherapy, instead, it is more and more timely, for just targeting the tumor “index-dominant lesion”, the resort to mpMRI/transrectal real-time ultrasound fusion imaging.  Quite recently, mpMRI/real-time transrectal ultrasound software-mediated digital co-registration has allowed to properly carry-out, in patients suffering from intermediate/high risk prostate carcinoma with mpMRI visible “index- dominant” intraprostatic nodule, the HDR ¹⁹² Ir transperineal temporary implant-brachytherapy  as accurate partial prostate radiation dose escalation supplemental to hypofractionated external beam radiotherapy [5,6].   

Given the interesting, even rare, reports on this subject, it would be advisable to widen the resort to the above-outlined mpMRI/transrectal  ultrasound fusion imaging-guided prostate cancer brachytherapy, particularly for a suitably targeted dominant tumor nodule detection/ablation.

 

Contardo Alberti

L D of Surgical Semeiotics, University of Parma, Parma, Italy

 

 References

1  Chao MW, Grimm P, Yaxley J, Jagavkar R, Ng M, Lawrentschuk N. Brachytherapy: state-of-the-art radiotherapy in prostate cancer. BJU Int  2015; 116(S3): 80-8. doi: 10.1111/bju.13252.

2  Shoji S, Hiraiwa S, Endo J, Hashida K, Tomonaga T, Nakano M et al. Manually controlled targeted prostate biopsy with real-time fusion imaging of multiparametric magnetic resonance imaging and stransrectal ulrasound :an early experience. Int J Urol 2015; 22(2): 173-8. doi: 10.1111/iju.12643.

 3  Marks L, Young S, Natarajan S.  MRI-ultrasound fusion for guidance of targeted prostate biopsy. Curr Opin Urol 2013; 23(1): 43-50. doi: 10.1097/MOU.0b013e32835ad3ee.

4  Woodrum DA, Kawashima A, Gorny KR, Mynderse LA. Magnetic resonance-guided thermal therapy for localized and recurrent prostate cancer. Magn Reson Imaging Clin N Am.2015; 23(4): 607-19. doi:10.1016/j.mric.2015.05.014

5  Bubley GJ, Bloch BN, Vazquez C, Genega E, Holupka E, Rofsky N, Kaplan I.  Accuracy of endorectal magnetic resonance/transrectal ultrasound fusion for detection of prostate cancer during brachytherapy. Urology 2013;81(6): 1284-9. doi: 10.1016/j.urology.2012.12.051.

6  Gomez-Iturriaga A, Casquero F, Urresola A, Ezquerro A, Lopez JI, Espinosa JM et al. Dose escalation to dominant intraprostatic lesions with MRI-transrectal  ultrasound fusion high-dode-rate prostate brachytherapy. Radiother Oncol 2016 Feb 15. doi: 10.1016/j.radonc.2016.02.004 (Epub ahead of print).

 

March #urojc: Radiotherapy for Prostate Cancer – Is it a gift that keeps on giving?

The International Urology Journal Club on Twitter is now well into its 4th year.  The subject for the March 2016 discussion was a paper published in the BMJ entitled Second Malignancies after radiotherapy for prostate cancer: systematic review and meta-analysis”.

Lead and senior authors, Chris Wallis and Rob Nam were kind enough to  make themselves available to participate in this discussion.  Rob Nam made use of the  #urojc guest twitter account.

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The literature was searched using Medline and Embase and the method of review was the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis of Observational studies in Epidemiology (MOOSE) guidelines for reporting of this systematic review and meta-analysis.

Chris Wallis provided an excellent TL:DR summary with the following tweet.

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It is well recognized that secondary malignancies following radiation exposure could take many years to become apparent.

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The responses were fairly predictable but nevertheless an important point to explore.

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Early in the discussion, there was also relevant reminder of the issue of differences in odds ratios and absolute risk.  That said, consideration needs to be given to the ‘big ticket’ nature of secondary malignancy where even a small absolute risk drives a great deal of interest in this subject matter.

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An interesting finding from the study was that the risk of secondary malignancy was less with brachytherapy compared with external beam radiation.

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Further to this, is it possible that there could be a difference between HDR and seed brachytherapy?  An interesting thought although not specifically covered in the paper.

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A more controversial aspect to the discussion was whether the risk of secondary malignancy would justify screening or surveillance. The following exchange was worthy of note.

Whilst there is nothing in the way of documented guidelines or actual evidence to demonstrate a benefit of surveillance, it seems something worthy of consideration for future practice guidelines –  in other words, recommendations one way or the other.

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Rob Nam refers to a third paper on radiation outcomes in the context of previous surgery.  This BJC paper, the Lancet Oncology paper (previous discussed at a #urojc in 2014) and now the current paper could cheekily be called the Nam Trilogy – make note that you heard this term here for the first time.

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To what extent should we be counseling our patients on the risk of secondary malignancy if they are to undergo radiation for prostate cancer?  Is this just another factor to encourage surgery over radiotherapy?  Will there be no change in practice, particularly in the US where many lucrative radiation oncology services are actually owned by urological surgeon private practice groups?

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The state of radiation oncology practice is different outside the US and my own personal thoughts on the matter are that the Nam Trilogy of papers will create a series of well cited ‘evidence’ that will further shift the weight of opinion towards surgery over radiotherapy as a primary treatment for localized prostate cancer.

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Anybody who followed the March installment of the #urojc would have been impressed by the high level of interaction by the authors Chris Wallis and Rob Nam.  A particular mention should be given to Sabin Motwani who as a radiation oncologist, provided valuable input to the discussion.

Please do join us for the April installment of the #urojc and I encourage you all to email, tweet or DM your suggestions for papers to be discussed.  Please also, feel free to volunteer to write up a monthly summary for publication on the BJUI blogs.  I would also like to acknowledge the contributions of Rustom Manecksha who was the winner of the 2016 BJUI SoMe Award for #urojc – a reflection to the quality of his participation and support for this online educational activity.

 

Henry Woo is an Associate Professor of Surgery at the Sydney Adventist Hospital Clinical School of the University of Sydney.  He is the coordinator of the International Urology Journal Club on Twitter.

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

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

 

 

Article of the Week: Complications following artificial urinary sphincter placement after RP and EBRT

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.

Complications following artificial urinary sphincter placement after radical prostatectomy and radiotherapy: A meta-analysis

Anthony S. Bates, Richard M. Martin* and Tim R. Terry

Department of Urology, Leicester General Hospital, University Hospitals of Leicester NHS Trust, Leicester, and *School of Social and Community Medicine, University of Bristol, Bristol, UK

Read the full article
OBJECTIVE

To conduct a systematic review and meta-analysis of artificial urinary sphincter (AUS) placement after radical prostatectomy (RP) and external beam radiotherapy (EBRT).

PATIENTS AND METHODS

There were 1 886 patients available for analysis of surgical revision outcomes and 949 for persistent urinary incontinence (UI) outcomes from 15 and 11 studies, respectively. The mean age (sd) was 66.9 (1.4) years and the number of patients per study was 126.6 (41.7). The mean (sd, range) follow-up was 36.7 (3.9, 18–68) months. A systematic database search was conducted using keywords, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Published series of AUS implantations were retrieved, according to the inclusion criteria. The Newcastle–Ottawa Score was used to ascertain the quality of evidence for each study. Surgical results from each case series were extracted. Data were analysed using CMA® statistical software.

RESULTS

AUS revision was higher in RP + EBRT vs RP alone, with a random effects risk ratio of 1.56 (95% confidence interval [CI] 1.02–2.72; P <0.050; I2 = 82.0%) and a risk difference of 16.0% (95% CI 2.05–36.01; P < 0.080). Infection/erosion contributed to the majority of surgical revision risk compared with urethral atrophy (P = 0.020). Persistent UI after implantation was greater in patients treated with EBRT (P <0.001).

CONCLUSIONS

Men receiving RP + EBRT appear at increased risk of infection/erosion and urethral atrophy, resulting in a greater risk of surgical revision compared with RP alone. Persistent UI is more common with RP + EBRT

Read more articles of the week

 

Editorial: Post-prostatectomy incontinence in the irradiated patient: more than just a drop in the ocean

Improved early detection of prostate cancer has led to an increased incidence of this disease, and an increase in the number of patients undergoing radical prostatectomy (RP). The rate of post-prostatectomy incontinence (PPI) is difficult to determine because of the varying definitions of incontinence, but approximately one in five men require the use of pads in the long term after RP. Incontinence has a significant negative impact on quality of life, and remains many men’s greatest fear, especially for the one in four who present at the age of <65 years. While significant advancements have been made in prostate cancer treatment, strong evidence for the optimum management of PPI remains lacking. Most guidelines are based on grade B or C recommendation and many questions about its surgical management remain unanswered.

The artificial urinary sphincter (AUS) has stood the test of time and has long been considered the ‘gold standard’ treatment for PPI, especially for those with moderate to severe incontinence. The quoted success rates achieved with this device vary from study to study based on the varying definition of ‘dry’. The use of radiotherapy (RT) after prostatectomy is generally considered to have a negative impact on its efficacy and revision rate, although some data have been conflicting. In this month’s BJUI, Bates et al. [1] present a timely and well-structured systematic review and meta-analysis of AUS placement after RP and RT. By analysing pooled results, the authors set out to clarify the effect of RT on AUS efficacy and outcomes. In total, 1886 patients from 15 studies published between 1989 and 2014 were included in the meta-analysis, including 14 studies assessing surgical revision and 11 looking at persistent urinary incontinence. No randomized controlled trials were available for analysis. Retrospective reporting and a lack of standardized postoperative validated assessments were a weakness of individual studies, and efforts to limit the effects of study heterogeneity and risk of bias were made using statistical models. The revision rate after a mean follow-up of 38.4 months was significantly higher in irradiated vs. non-irradiated men (mean 37.3 vs 19.8%; P < 0.007); the risk ratio was 1.56 and number needed to harm was 4 (i.e. one surgical revision for every four AUS devices implanted in irradiated men). Infection/erosion and urethral atrophy accounted for approximately half and one-third of all revisions respectively. Persistent urinary incontinence was also more than twice as likely in irradiated vs non-irradiated men (29.5 vs 12.1%; P = 0.003; risk ratio 2.08, number needed to harm 9).

This study highlights the significant negative impact of RT after RP on functional outcomes and its treatment. This is particularly important considering that approximately one-third of patients will require adjuvant or salvage radiotherapy at some stage after RP. The development of incontinence after RT is primarily attributable to the negative effect of radiation on bladder and urethral tissue. Unlike outcomes with regard to erectile function, the type of primary surgery performed (open vs robotic) does not appear to have any significant impact on PPI [2]. Timing of RT also does not seem to affect function, with similar rates of incontinence reported for early (<6 months after RP) vs late (>6 months after RP) irradiation reported 3 years after RT (24.5 vs 23.3%, respectively; P = 0.79) [3].

New devices, such as the male sling, have increased the options for PPI treatment. Male slings have achieved popularity because of their safety, relative ease of insertion and patients’ strong desire to void naturally without fiddling with pumps. Kumar et al. [4] reported that one in four men who were recommended an AUS as the best option by their surgeon chose a sling; 92% who were offered either also opted against the gold standard AUS. Slings, however, have not fared well in patients with severe incontinence or those who have undergone RT. Pooled analysis of the AdVance® sling reported ‘success’ rates of 56 and 54%, respectively, in these scenarios, compared with a mean overall ‘success’ rate of 75% [5]. Reported success, however, does not equate to being ‘dry’, as reported in many AUS studies, and this lack of uniformity in describing outcomes prevents adequate clarity when comparing different devices. Despite the lower success rate after RT, slings, unlike the AUS, do not appear to have any additional complications in this setting [1, 6], and sling failure does not appear to prejudice subsequent AUS placement [7].

To date, no randomized controlled trial has directly compared efficacy of the newer slings with the AUS. Well-designed trials, with standardized protocols and uniform long-term assessments of outcome, including complications and quality of life, are required to clarify their place in managing PPI. Current randomized controlled trials are evaluating these devices prospectively, and will provide much needed level 1 evidence in this field. The most interesting of these is the MASTER trial (Male synthetic sling vs Artificial urinary Sphincter Trial). This multicentre UK randomized controlled trial is for men with incontinence after prostate surgery for cancer or benign disease [8]. Patients of any age, with any level of incontinence are eligible, and previous RT is not an exclusion criterion. The trial aims to randomize 360 men and will also follow up 360 non-randomized men, and runs until 2019. This trial will help clarify the relative benefits of the devices by incontinence severity. It will also provide some prospective data on the effect of RT on outcomes, although the 2-year follow-up will be too short to evaluate this fully.

The question remains regarding which strategy is the best for post-prostatectomy irradiated patients. Until the results of good quality trials are available, the jury is out. The AUS remains the gold standard in this setting, for now. For patients with mild to moderate incontinence, the sling is an option, and offers some advantages, but offers a lower overall chance of becoming pad free. Patients must be carefully counselled about the risk/benefit of this approach compared with an AUS. Results of the MASTER trial will help better define management of this subgroup. For moderate to severe incontinence, the AUS is the gold standard, albeit with an increased risk of failure and revision. The present meta-analysis arms the clinician with much needed data to quantify the relative risk of complications and adverse outcomes in this setting, and will allow better counselling and management of patient’s expectations.

Read the full article

Majid Shabbir

Department of Urology, Guy’s Hospital, London, UK

References

1 Bates A, Martin R, Terry T. Complications following artificial urinary sphincter placement after radical prostatectomy and radiotherapy: a metaanalysis. BJU Int 2015; 116: 623–33

2 Haglind E, Carlsson S, Stranne J et al. Urinary incontinence and erectile dysfunction after robotic versus open radical prostatectomy: a prospective, controlled, nonrandomised trial. Eur Urol 2015. doi: 10.1016/j.eururo. 2015.02.029. [Epub ahead of print]

3 Sowerby RJ, Gani J, Yim H. Long-term complications in men who have early or late radiotherapy after radical prostatectomy. Can Urol Assoc J 2014; 8: 253–8.

4 Kumar A, Litt ER, Ballert KN, Nitti VW. Artificial urinary sphincter versus male sling for post-prostatectomy incontinence-what do patients choose? J Urol 2009; 181: 1231–5.

5 Van Bruwaene S, Van der Aa F, De Ridder D. Review: the use of sling versus sphincter in post-prostatectomy urinary incontinence. BJU Int 2015; 116: 330–42

6 Zuckerman JM, Tisdale B, McCammon K. AdVance male sling in irradiated patients with stress urinary incontinence. Can J Urol 2011; 18: 6013–7.

7 Lentz AC, Peterson AC, Webster GD. Outcomes following artificial sphincter implantation after prior unsuccessful male sling. J Urol 2012; 187: 2149–53.

8 Abrams P. Male synthetic sling versus Artificial urinary Sphincter Trial for men with urodynamic stress incontinence after prostate surgery: Evaluation by Randomised controlled trial (MASTER), 2014. Available at: www.controlled-trials.com/ISRCTN49212975/MASTER. Accessed May 2015

 

Video: Complications following AUS placement after RP and radiotherapy

Complications following artificial urinary sphincter placement after radical prostatectomy and radiotherapy: a meta-analysis

Anthony S. Bates1,*, Richard M. Martin2 and Tim R. Terry1

1Department of Urology, Leicester General Hospital, University Hospitals of Leicester NHS Trust, Leicester, UK 2School of Social and Community Medicine, University of Bristol, Bristol, UK

Read the full article
Objective

To conduct a systematic review and meta-analysis of artificial urinary sphincter (AUS) placement after radical prostatectomy (RP) and external beam radiotherapy (EBRT).

Patients and Methods

There were 1 886 patients available for analysis of surgical revision outcomes and 949 for persistent urinary incontinence (UI) outcomes from 15 and 11 studies, respectively. The mean age (sd) was 66.9 (1.4) years and the number of patients per study was 126.6 (41.7). The mean (sd, range) follow-up was 36.7 (3.9, 18–68) months. A systematic database search was conducted using keywords, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Published series of AUS implantations were retrieved, according to the inclusion criteria. The Newcastle–Ottawa Score was used to ascertain the quality of evidence for each study. Surgical results from each case series were extracted. Data were analysed using CMA® statistical software.

Results

AUS revision was higher in RP + EBRT vs RP alone, with a random effects risk ratio of 1.56 (95% confidence interval [CI] 1.02–2.72; P < 0.050; I2 = 82.0%) and a risk difference of 16.0% (95% CI 2.05–36.01; P < 0.080). Infection/erosion contributed to the majority of surgical revision risk compared with urethral atrophy (P = 0.020). Persistent UI after implantation was greater in patients treated with EBRT (P < 0.001).

Conclusions

Men receiving RP + EBRT appear at increased risk of infection/erosion and urethral atrophy, resulting in a greater risk of surgical revision compared with RP alone. Persistent UI is more common with RP + EBRT.

 

Read more articles of the week

 

 

Radiation within urology: challenges and triumphs

As gatekeepers urologists remain at the frontline of urological oncology in a position of trust that they have held since Charles Huggins, Nobel Laureate in Urology, pioneered the use of hormone manipulation to treat prostate cancer. However, radiation within urology is an important adjunctive, palliative and even primary treatment method for many urological malignancies. However, within many spheres, particularly internationally regarding prostate cancer, tensions appear to have been simmering between urologists and radiation oncologists. Fortunately, this does not appear to be the case in Australia and New Zealand but it is an important time to reflect on such issues as we move ever forward in the multimodality era.

In the USA the use of self-referral by urologists of men for adjuvant radiotherapy (RT) has come under scrutiny. Some urology groups have integrated intensity modulated RT (IMRT), a RT treatment carrying a high reimbursement rate, into their practice. This was highlighted in a recent New England Journal of Medicine article where the rate of IMRT use by urologists working at National Comprehensive Cancer Network centres remained stable at 8% but increased by 33% among matched self-referring urology groups [1]. This study has been criticised for bias but nonetheless captured political and academic attention. Certainly this situation has not arisen in our hemisphere but it remains important we think critically of what treatments we offer our patients and ensure patient’s best interests are maintained.

Clearly more research is required as to who should be receiving adjuvant RT and at what stage. In the latest issue of the BJUI USANZ supplement we highlight the Radiotherapy – Adjuvant vs Early Salvage (RAVES) trial for prostate cancer biochemical failure and high-risk disease [2]. There is no doubt this is an important trial because to date we have been unable to establish exactly which patients should receive adjuvant RT and when. Recruitment has been challenging as patients doing well after surgery often do not want additional treatment and a very small subset who are still recovering want to be enrolled but due to timing missing eligibility. Enthusiastic patients also may demand treatment rather than be randomised. Critics would also argue that the trial can never really answer the question because many men not requiring adjuvant RT will receive it [3]. Ongoing support of all parties should achieve accrual and in time, robust data. Excitingly imaging with MRI and other modalities will ensure further trials to assist in identifying disease in the salvage setting making choices easier based on more objective data [4].

 

Read the USANZ Supplement

Consumerism has driven robotic surgery [5] and is doing the same for RT but descriptions of treatment would be better placed to remain generic. The use of the term ‘radiosurgery’ has highlighted the shift away from the term ‘radical radiotherapy’. Of course the term ‘robot’ has become synonymous with radical prostatectomy but the ‘radical’ contribution remains and interestingly the term ‘robot’ has been trialled by radiotherapists: ‘image-guided robotic radiosurgery’ or its other more commonly used term Cyberknife® (Accuracy Incorporated, Sunnyvale, CA, USA). Certainly this would be more accurately known as stereotactic body RT (SBRT). It is these terminology changes and continual shifts in treatment regimens that rankles many, with the old argument that RT treatment was done with inferior technology so results should be ignored receives disproportionate use at conferences. All groups need to acknowledge treatments have improved rather than disowning data from older treatment regimes. On the counter side one example from brachytherapy [6] concluded that despite the hype of improving dosimetry and reducing complications, the preoperative condition regarding erectile function and LUTS are the most important factors regarding postoperative outcome. This is almost certainly true for surgery as well. Comparison of side-effects appears unfair with grading of radiation toxicities more lenient than Clavien listed complications – an even playing field for comparison of complications is warranted.

Multimodality treatment for high-risk disease is becoming the standard of care. Urologists are beginning to embrace this regime of planned surgery with likely RT and ultimately systemic therapies. However, radiation oncologists often prefer to use radiation and hormonal manipulation and consider this ‘modified monotherapy’. Some men receive different modes of RT with concerns this leads to significantly more complications and in combination with androgen deprivation comes with all of the secondary effects of such therapy. An ideal study for such high-risk patients would randomise men to RT and androgen deprivation vs a graded multimodality treatment starting with surgery and then progressing to RT and systemic therapies when required (as some men will have T2 or T3a disease with clear margins that can be observed for a PSA rise necessitating treatment).

Complications do develop after any therapy and urologists are expertly placed to deal with them. Yet, there is a belief that RT and its long-term effects are real and these are often underplayed. This is contributed by a paucity of follow-up data beyond 5 years with primary RT. Major problems from surgery are generally able to be repatriated. However, the same may not be stated for RT complications: cystitis, stricture disease, permanent catheter drainage and chronic pain syndromes although uncommon, are not rare events and not easily remedied due to the altered tissues. Urologists are able to assist with these conditions but some feel that their efforts are unrecognised and that they share too much of the burden from somewhat surprised patients when situations are not able to be satisfactorily resolved. This reinforces the involvement by enthusiastic urologists with the patient selection and follow-up of brachytherapy and even other RT treatments being the cornerstone for ideal patient management and success.

Other areas worthy of engagement are with patients who develop a recurrence after RT treatment where the available data are sparse, making a decision even more difficult [3]. The perceived reluctance to refer RT failures to urologists in a timely fashion meaning many men are not offered salvage surgery or other options [7]. Occasionally urologists do the same with surgical failures but with multi-disciplinary teams, this is a rare event.

Communication remains a key to a multidisciplinary approach. Against the successes and strains, there are newer developments that will conspire to bring teams closer together, such as newer systemic therapies and the consideration of RT in men with oligometastatic disease. Also, based on Surveillance, Epidemiology and End Results (SEER) data, it appears that patients with limited metastatic disease may benefit from having treatment of the primary disease with a significant decrease in mortality (slightly more pronounced with surgery than radiation) [8]. This will ensure further debate on how far we stretch our primary treatment boundaries for the betterment of patients. Finally, use of fiducial markers and spacers will hopefully minimise morbidity and these are discussed in this supplement [9].

Just like any long-term relationship, the balance will shift at times and there has to be give and take on both sides. Many of the points in this editorial could be switched the other way with urologists at fault, so we must always be careful to be global, and not focal in our approaches. With everyone working together we have improved outcomes and survival of many with many urological malignancies. Overall, there is still harmony but room for even greater communication and collaboration as we strive towards better outcomes in future decades.

Nathan Lawrentschuk
University of Melbourne, Department of Surgery and Ludwig Institute for Cancer Research, Austin Hospital and Peter MacCallum Cancer Centre, Department of Surgical Oncology, Melbourne, VIC, Australia

Read the USANZ Supplement

References

  1. Mitchell JM. Urologists’ use of intensity-modulated radiation therapy for prostate cancerN Engl J Med 2013; 369: 1629–1637
  2. Pearse M, Fraser-Browne C, Davis ID et al. A Phase III trial to investigate the timing of radiotherapy for prostate cancer with high-risk features: background and rationale of the Radiotherapy – adjuvant versus Early Salvage (RAVES) trialBJU Int 2014; 113: 7–12
  3. Chen RC. Making individualized decisions in the midst of uncertainties: the case of prostate cancer and biochemical recurrence. Eur Urol 2013; 64: 916–919
  4. Thompson J, Lawrentschuk N, Frydenberg M, Thompson L, Stricker P. The role of magnetic resonance imaging in the diagnosis and management of prostate cancer. BJU Int 2013; 112 (Suppl. 2): 6–20
  5. Alkhateeb S, Lawrentschuk N. Consumerism and its impact on robotic-assisted radical prostatectomy. BJU Int 2011; 108:1874–1878
  6. Meyer A, Wassermann J, Warszawski-Baumann A et al. Segmental dosimetry, toxicity and long-term outcome in patients with prostate cancer treated with permanent seed implantsBJU Int 2013; 111: 897–904
  7. de Castro Abreu AL, Bahn D, Leslie S et al. Salvage focal and salvage total cryoablation for locally recurrent prostate cancer after primary radiation therapyBJU Int 2013; 112: 298–307
  8. Cheng J. Would you really do a radical prostatectomy on a man with known metastatic prostate cancer? BJU Int BLOG posted 09 December 2013. Available at: https://www.bjuinternational.com/bjui-blog/would-you-really-do-a-radical-prostatectomy-on-a-man-with-known-metastatic-prostate-cancer/. Accessed January 2014
  9. Ng M, Brown E, Williams A, Chao M, Lawrentschuk N, Chee R. Fiducial markers and spacers in prostate radiotherapy: current applicationsBJU Int 2014; 113: 13–20
 

Surgery or Radiation in Prostate Cancer?

I am sure many of you are familiar with the clinical situation I see every week of a man with newly-diagnosed prostate cancer asking me about his options. While we steer many men with low risk prostate cancer towards surveillance nowadays, for those with intermediate or high risk disease intervention is usually their best option, especially if they have a long life expectancy. This gives us the dilemma of whether to recommend surgery or radiotherapy.

In Oxford, we have a long and pioneering history of evidence-based medicine, and I lament the lack of RCTs in this field. The only one, ProtecT, which is being led also by Oxford, will not report before 2016, and will at least in part be subject to volunteer bias. Now, the question of surgery or radiotherapy for prostate cancer is not a new question. Millions of men have undergone these treatments across the globe and over the decades, and many other investigators have evaluated this question.

Most of these previous studies suggest that surgery in indeed superior but the main problem with them is inadequate control for selection bias (what we term in the trade as confounding by indication) – i.e. that men undergoing surgery are fitter and have better prognosis from their cancer point of view than men undergoing radiotherapy, and thus it’s not a fair comparison. Another problem with these previous studies is that the datasets used are not very comprehensive – not all men are included, and we don’t know all their important risk factors. All this makes it difficult to be confident in their results.

What is different about the BMJ study (https://www.bmj.com/content/348/bmj.g1502) is that the dataset and the statistics were top-notch. More than 98% of men diagnosed with prostate cancer in Sweden from 1998 onwards were included, and virtually all important data points were recorded with <2% incomplete data. Men were followed for up to 15 years and 4 different sets of statistical models were done to balance the surgery and radiotherapy groups with each other.

Remarkably, all sets of models came up with the same answer: that surgery led to better survival results than radiotherapy, especially for the men with intermediate and high risk prostate cancer and even more so if they had a long life expectancy. If I were a barrister, I would say this study provides strong evidence to build the case that surgery is a better option in survival terms for the majority of men who need treatment for localized prostate cancer.  Medicine, like law, is never about absolutes, it’s about risk and probability. Can I prove that surgery is better than radiotherapy from this study – no; but there certainly seems a strong case to argue.

The current BJUI Article of the Week is another excellent article on the same subject (https://www.bjuinternational.com/article-of-the-week/prostate-cancer-sun-shines-light-on-surgical-survival/)

You can download Drs Sooriakumaran & Wiklund’s slideshow on their article by clicking here (1.5mb)

Prasanna Sooriakumaran is a robotic prostate & bladder cancer surgeon and academic at Oxford and Karolinska. @PSooriakumaranu

 

Article of the week – Prostate cancer: Sun shines light on surgical survival

Every week the Editor-in-Chief selects the 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 vs radiotherapy vs observation among older patients with clinically localized prostate cancer: a comparative effectiveness evaluation

Maxine Sun*, Jesse D. Sammon, Andreas Becker*, Florian Roghmann*, Zhe Tian*, Simon P. Kim, Alexandre Larouche*, Firas Abdollah*, Jim C. Hu§, Pierre I. Karakiewicz* and Quoc-Dien Trinh**

*Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada, VUI Center for Outcomes Research, Analytics and Evaluation, Henry Ford Health Systems, Detroit, MI, Department of Urology, Yale University, New Haven, CT, §Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA, Department of Urology, University of Montreal Health Center, Montreal, Canada and **Department of Surgery, Division of Urology, Brigham and Women’s Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

MS and J.D.S contributed equally to the work.

Read the full article
OBJECTIVE

• To compare efficacy between radical prostatectomy (RP), radiotherapy and observation with respect to overall survival (OS) in patients with clinically localized prostate cancer (PCa).

METHODS

• Using data (1988–2005) from the Surveillance, Epidemiology, and End Results–Medicare linked database, 67 087 men with localized PCa were identified.

• The prevalence of the initial treatment strategy was quantified according to patients’ life expectancy ([LE] <10 vs ≥10 years) at initial diagnosis and according to tumour stage. To reduce the unmeasured bias associated with treatment, we performed an instrumental variable analysis.

• Stratified (by stage and LE) Cox regression and competing-risks regression analyses were generated for the prediction of OS and cancer-specific mortality, respectively.

RESULTS

• Among patients with <10 years of LE, most were treated with radiotherapy (49%) or observation (47%). Among patients with ≥10 years of LE, most received radiotherapy (49%), followed by RP (26%).

• In men with <10 years of LE, RP and radiotherapy were not different with respect to OS (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.45–1.48, P = 0.499). Conversely, in men with ≥10 years of LE, RP was associated with an improved OS compared with observation (HR: 0.59, 95% CI: 0.49–0.71, P < 0.001) and radiotherapy (HR: 0.66, 95% CI: 0.56–0.79, P < 0.001).

• Similar results were recorded in competing-risks regression analyses.

CONCLUSION

• In patients with an estimated LE ≥10 years at initial diagnosis, RP was associated with improved survival compared with radiotherapy and observation, regardless of disease stage.

Editorial – Prostate cancer surgery vs radiation: has the fat lady sung?

The current article by Sun et al. [1] representing a number of institutions involved in prostate cancer treatment provision is thought-provoking and hypothesis-generating. The authors contention when mining Surveillance, Epidemiology and End Results data for 67 000 men who had localized prostate cancer between 1988 and 2005 is that those with a life expectancy >10 years had less likelihood of prostate cancer death when treated with surgery rather than by radiotherapy or being left to observation. The Scandinavians have already shown, in the randomized study by Hugosson et al. [2], that if you have your prostate cancer removed you have less likelihood of symptomatic local recurrence, lower likelihood of metastasis and progression, and a 29% reduced likelihood of prostate cancer death. The current study asks the question ‘Is radiation therapy less likely to provide a long-term cure for prostate cancer than surgery?’ and gives an answer in the affirmative.

The current paper, in its way, neatly encapsulates the contemporary angst generated in the community when prostate cancer screening, diagnosis and therapy are discussed. The Prostate, Lung, Colorectal, and Ovarian Cancer Screening (PLCO) trial [3] allegedly shows no benefit from treatment over observation and contends perhaps that we surgeons and radiation oncologists are harm-workers, not life-savers. The PLCO has a 52% PSA contamination in its control arm [3]. That flawed trial compared screening with de facto screening and produced, in my view, a null hypothesis. How do we explain the paradox of a 44% reduction in prostate cancer-specific mortality between 1993 and 2009? How do we explain the disconnect between these trials and the facts? What do we do with the data not yet considered by the expert panels showing that early PSA testing at age <50 years is highly predictive of subsequent lethal prostate cancer? [4]

Clinicians are rapidly moving to an era of judicious risk assessment. This can only be done after biopsy is performed. We now frequently enrol patients with apparently indolent prostate cancer into surveillance protocols [5]. So the question should be ‘If the disease found on biopsy is moderate to high risk, and potentially lethal for that man, should we remove his prostate surgically or radiate it with intensity-modulated radiation therapy, brachytherapy, proton therapy, +/- hormone therapy?’.

As a surgeon I have an inherent dislike of combining hormone therapy in primary treatment. At least 50% of men in high-risk prostate cancer cohorts who receive radiation therapy also receive hormone therapy as adjuvant or neoadjuvant treatment [6]. Hormone therapy has a myriad of side effects. Even if the playing field was level between surgery and radiation therapy, the avoidance of hormone therapy as a first-line treatment gives surgery a seductive advantage.

The authors of the current report show a significant survival advantage in the cohort for surgery over radiation therapy and observation. There will never be a randomized trial between the two potentially curative treatment methods surgery and radiation. The scourge of commercial interest with spurious claims of superiority of one form of therapy over another, proton beam vs intensity-modulated radiation therapy, robotics vs high-intensity focused ultrasonography, means that we risk having our decisions regarding appropriate therapy formed by multibillion dollar technology companies with powerful marketing capacity. The current paper confirms what is self-evident: untreated localized prostate cancer can be lethal. Surgery and radiation therapy lower the morbidity and mortality from prostate cancer. Which is the better method of curative therapy is moot, but we do know that cure is very much predicated on the expertise and location of the practitioner.

We know mostly when and who to treat and what treatments work well. In my view, the prostate cancer testing debate resonates with the contemporary discussion about childhood immunization for infectious diseases. Some parents now, who clearly cannot remember the devastating epidemics of polio and other childhood illnesses, refuse to immunize their children. Prostate cancer practitioners who did not live in the quite recent era where the initial presentation of prostate cancer was bone metastasis +/− crush fracture to the vertebra and sometimes paraplegia, may be unknowingly steering us backwards.

At the recent 2013 AUA meeting, Adams et al. [7] reported on the fate of men not screened for prostate cancer, i.e. those men who presented with a PSA >100 ng/mL. There was a 3-year survival rate of 9.7%, a 19.7% cord compression rate and a 64% hospitalization rate. Those who do not learn the lessons of history are condemned to repeat them.

Anthony J. Costello
Department of Surgery, Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia

Read the full article

References

  1. Sun M, Sammon JD, Becker A et al. Radical prostatectomy vs radiotherapy vs observation among older patients with clinically localized prostate cancer: a comparative effectiveness evaluationBJU Int 2014; 113: 200–208
  2. Hugosson J, Carlsson S, Aus G et al. Mortality results from the Goteborg randomised population-based prostate-cancer screening trialLancet Oncol 2010; 11: 725–732
  3. Andriole GL, Crawford ED, Grubb RL 3rd et al. Prostate cancer screening in the randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: mortality results after 13 years of follow-upJ Natl Cancer Inst 2012; 104: 125–132
  4. Vickers AJ, Ulmert D, Sjoberg DD et al. Strategy for detection of prostate cancer based on relation between prostate specific antigen at age 40–55 and long term risk of metastasis: case-control studyBMJ 2013; 346: f2023
  5. Evans SM, Millar JL, Davis ID et al. Patterns of care for men diagnosed with prostate cancer in Victoria from 2008 to 2011Med J Aust 2013; 198: 540–545
  6. Cooperberg MR, Vickers AJ, Broering JM, Carroll PR. Comparative risk-adjusted mortality outcomes after primary surgery, radiotherapy, or androgen-deprivation therapy for localized prostate cancerCancer 2010; 116: 5226–5234
  7. Adams W, Elliott CS, Reese JH. The fate of men presenting with PSA over 100 ng/mL: what happens when we do not screen for prostate cancer? AUA 2013. Abstract 2696

 

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