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Editorial: Penile vibratory stimulation (PVS) a novel approach for penile rehabilitation post nerve sparing radical prostatectomy

The reported incidence of erectile dysfunction (ED) after nerve-sparing radical prostatectomy (NS-RP) varies in the literature from 30 to 80% [1]. This can be explained by the state of neuropraxia which affects the cavernosal nerves, even if the nerves are anatomically intact. During this period there is a lack of nocturnal tumescence which leads to tissue hypoxia and ischaemic damage to the cavernosal smooth muscles leading to smooth muscle necrosis and fibrosis, which in turn causes veno-occlusive dysfunction (VOD). A study by Mulhall et al. [2] showed that, at 12 months after NS-RP, 50% of patients will have VOD and ED. The role of penile rehabilitation, therefore, is to maintain adequate tissue oxygenation until the cavernosal nerves recover with the return of the spontaneous nocturnal tumescence; thus, penile rehabilitation should not be confused with ED treatment. If you see yourself as religious, addiction may make you feel guilty or get you to feel isolated among your friends at your religious organization. A spiritual Christian rehab center in Orlando may be the right choice for you. Not only do you get to meet like-minded people to share your experiences in your journey to sobriety, but the process may also help you to rediscover your faith in God. Legacy Healing Center Tampa offer programs that make spiritual guidance an important part of every type of addiction treatment. Orange County law enforcement has taken steps to make sure the drugs are not as easily available as they once were. This has helped manage Orlando’s drug problem and kept it from turning worse. As important as prevention is to saving lives, however, to the hundreds who are already addicted, rehab is what helps. If you are religious or spiritual, faith-based drug rehab can be the answer to the challenges that you face. It’s important to remember that faith-based rehab only works well for those who are deeply spiritual or religious. Trying faith-based rehab when you are ambivalent about religion can work against you. You may find that you aren’t able to accept what you’re asked to practice, and you may find yourself rebelling. It’s important to choose a treatment approach that you can go along with in good conscience.

Several lines of treatment, including phosphodiesterase 5 inhibitors, intracavernous injection of alprostadil and vacuum pump therapy, have been used in penile rehabilitation but an agreed rehabilitation programme in terms of agents used, timing and duration of therapy does not yet exist [1].

The present study by Fode et al. [3] reports a novel approach to penile rehabilitation using penile vibratory stimulation (PVS). The study looked into the effect of PVS on postoperative erection and continence. The Ferticare® vibrator (Fig. 1) was used at an amplitude of 2 mm and a vibration frequency of 100 Hz and applied to the frenulum once daily, with a sequence consisting of 10 s of stimulation followed by a 10-s rest and repeated 10 times.

The results showed a trend towards better erection in the PVS group (n = 30) compared with the control group (n = 38) as evidenced by the higher International Index of Erectile Function (IIEF) score, but the difference was not significant (P = 0.09). After 1 year, 16 patients (53%) in the PVS group had an IIEF score ≥18 compared with 12 (32%) patients in the control group (P = 0.07). The results did not show any effect of treatment on continence; at 12 months, 90% of the PVS group achieved continence compared with 94.7% of the control group (P = 0.46), although the PVS group had a significantly higher preoperative LUTS score which may explain the results.

The theory postulated is that application of PVS activates the parasympathetic erectile spinal centre (S2–S4), which in turn leads to activation of the cavernosal nerves, enhancing the healing process, and recovery from neuropraxia and restoration of spontaneous erections. Also this would lead to stimulation of the somatic S2–S4 spinal centre, which controls the pelvic floor muscles via the pudendal nerve, leading to the recovery of continence. Although this has been shown in patients with spinal cord injury as the authors mentioned; this may not be the case in post NS-RP with the nerves in a state of neurapraxia, whereas in patients with spinal cord injury the nerves are intact. It would have been of great value to conduct neurophysiological tests on these patients to demonstrate that, despite the cavernosal nerves being in a state of neurapraxia, nerve activity in response to PVS was actually present.

The rehabilitation protocol used in the present study started early but only continued for 6 weeks postoperatively. Studies have shown that the potential recovery time of erectile function after NS-RP is 6–36 months, with the majority recovering within 12–24 months [1,4]. The results might have shown statistical significance in favour of PVS, had treatment continued for a longer period. Starting PVS treatment in the early postoperative period may not be suitable in all patients; in this study six out of 36 patients (16.6%) were non-compliant with the protocol; four had prolonged catheterization and two experienced pain. Furthermore, neurophysiological testing is required to show that in the early postoperative period the cavernosal nerves are actually intact and therefore respond to PVS.

Although the results of the present study did not reach significance, they are encouraging, as there was a trend in favour of treatment with regard to erectile function. Further studies involving larger numbers of patients are warranted to investigate this new line of rehabilitation.

Amr Abdel Raheem* and David Ralph
*Andrology Department, Cairo University Hospital, Cairo, Egypt, and St. Peter’s Andrology Centre, Institute of Urology, London, UK

References

  1. Mulhall JP, Bivalacqua TJ, Becher EF. Standard operating procedure for the preservation of erectile function outcomes after radical prostatectomy. J Sex Med 2013; 10: 195–203
  2. Mulhall JP, Slovick R, Hotaling J et al. Erectile dysfunction after radical prostatectomy: hemodynamic profiles and their correlation with the recovery of erectile function. J Urol 2002; 167: 1371–5
  3. Fode M, Borre M, Ohl D, Lichtbach J, Sønksen J. Penile vibratory stimulation in the recovery of urinary continence and erectile function after nerve-sparing radical prostatectomy: a randomized, controlled trial. BJU Int 2014; 114: 111–7
  4. Rabbani F, Schiff J, Piecuch M et al. Time course of recovery of erectile function after radical retropubic prostatectomy: does anyone recover after 2 years? J Sex Med 2010; 7: 3984–90

Video: Penile vibratory stimulation after radical prostatectomy

Penile vibratory stimulation in the recovery of urinary continence and erectile function after nerve-sparing radical prostatectomy: a randomized, controlled trial

Mikkel Fode*, Michael Borre, Dana A. Ohl, Jonas Lichtbach§ and Jens Sønksen*

*Department of Urology, Herlev University Hospital, Herlev, Department of Urology, Aarhus University Hospital, Aarhus, Denmark, Department of Urology, University of Michigan, Ann Arbor, MI, USA, and §Department of Physiotherapy, Herlev University Hospital, Herlev, Denmark

OBJECTIVE

• To examine the effect of penile vibratory stimulation (PVS) in the preservation and restoration of erectile function and urinary continence in conjunction with nerve-sparing radical prostatectomy (RP).

PATIENTS AND METHODS

• The present study was conducted between July 2010 and March 2013 as a randomized prospective trial at two university hospitals. Eligible participants were continent men with an International Index of Erectile Function-5 (IIEF-5) score of at least 18, scheduled to undergo nerve-sparing RP.

• Patients were randomized to a PVS group or a control group. Patients in the PVS group were instructed in using a PVS device (FERTI CARE® vibrator).

• Stimulation was performed at the frenulum once daily by the patients in their own homes for at least 1 week before surgery. After catheter removal, daily PVS was re-initiated for a period of 6 weeks.

• Participants were evaluated at 3, 6 and 12 months after surgery with the IIEF-5 questionnaire and questions regarding urinary bother. Patients using up to one pad daily for security reasons only were considered continent. The study was registered at https://clinicaltrials.gov/ (NCT01067261).

RESULTS

• Data from 68 patients were available for analyses (30 patients randomized to PVS and 38 patients randomized to the control group).

• The IIEF-5 score was highest in the PVS group at all time points after surgery with a median score of 18 vs 7.5 in the control group at 12 months (P = 0.09), but the difference only reached borderline significance.

• At 12 months, 16/30 (53%) patients in the PVS group had reached an IIEF-5 score of at least 18, while this was the case for 12/38 (32%) patients in the control group (P = 0.07).

• There were no significant differences in the proportions of continent patients between groups at 3, 6 or 12 months. At 12 months 90% of the PVS patients were continent, while 94.7% of the control patients were continent (P = 0.46).

CONCLUSION

• The present study did not document a significant effect of PVS. However, the method proved to be acceptable for most patients and there was a trend towards better erectile function with PVS. More studies are needed to explore this possible effect further.

 

A new take on GPS navigation? Summary of the June #urojc twitter debate.

The diagnosis and management of prostate cancer continues to rapidly evolve, with heavy debates at each stage of the evolution process. The key trade off between avoiding the over diagnosis and overtreatment of low risk indolent tumours, versus failing to diagnose and act on what may progress to aggressive disease, is an on going theme in the debate.

Research into various diagnostic tools to help both the patient and clinician stratify individual risk is on going, however the heavy consequence of undertreating perhaps leads more into active treatment than clinically necessary.

The June #urojc twitter debate focused on the new and hugely important paper by Klein E et al, to which we were given open access to courtesy of European Urology.  The authors of this US study focus on the potential underuse of Active Surveillance (AS), and propose a Genomic Prostate Score in order to help risk stratify patients considering both surveillance and active therapy. Based on three studies, a prostatectomy study, a biopsy study, and a validation study, a 17-gene assay was created which was shown to predict both high stage and high grade disease at diagnosis.

The debate kicked off with the suggestions from the hosts that at genomics may make their way into AS protocols

 

Which was rapidly agreed

However inevitably the issue of cost was raised

Parth Modi praised the study design and results, however raised a valid question

And the further issue of logistics of samples provided for genomic testing was debated

With the possibility of low disease volume in samples contributing

Which launched a debate as to whether for those with low volume disease, the discussion of opting for genomics was a discussion too far

Alternatives to genomics in predicting progressive disease were discussed. However again the cost of these tests were debated – although generally thought to be less expensive than genomic testing.

 

Followed by perhaps an early contender for best tweet…

 

The host again posed an on point question

With responses suggesting there remains room for further work until genomics plays a role in day-to-day treatment plans

David Canes helped to put the debate into real terms by using an example case for discussion, which raised the point of interpretation of results being dependent on likely treatment decision, not necessarily treatment decision based fully on results

Which raised some slightly more pragmatic suggestions

GPS results however are not necessarily clear-cut. Like all prognostic indicators, they can be interpreted in variable ways. Is there a possibility that they could add to the quagmire in the decision making process for patients?

Ultimately the theme of the debate was summed up excellently by Matt Cooperberg. GPS is not offering a definitive strategy to decide who will and will not progress, or who should decide on active treatment. It does however mark a movement into individualised care, which may well be the future for prostate cancer treatment

Congratulations to David Canes for winning the Best Tweet prize which is a complimentary manuscript to Research Reports in Urology published by @DovePress.

Many thanks to all of those who participated in the debate. We look forward to next month’s #urojc discussion!

Sophia Cashman is a first year urology trainee working in the East of England region, UK. Her main areas of interest are female and functional urology. @soph_cash

 

New technology for prostate cancer…beyond robotics!

Urology has led the way introducing new technology for men with prostate cancer. Robotic surgery, focal therapy, nanoknife, cyberknife – the list goes on. But have we fully embraced the everyday technology we all have access to in our care for men with prostate cancer? There are a growing number of Apps designed to support prostate cancer patients and improve quality of life. If you type ‘prostate’ into the iTunes App store about 82 results are found, but many of these are fundraising events, journals and staging tools, many of which are not patient friendly. Whilst there is an increasing appetite for patient-centered tools – focused on supporting and empowering patients in managing their health and wellbeing – we still have some way to go in this regard.

As a clinical psychologist working in urology, I often hear patients and their families describing their feelings of uncertainty and loss of control. Furthermore, Australia is a huge country with vast rural and remote areas and many patients that live in these areas find it very difficult to access the information, advice and support they require to ensure optimal outcomes from their prostate cancer.

The benefits of harnessing technology in the pursuit of improved health and wellbeing via improved patient engagement and access to services are clear; so why not use this technology to improve the care we provide to men with prostate cancer?

We have developed an online prostate cancer portal www.PROSTMATE.org.au

PROSTMATE provides tailored information, access to self-help interventions, a personal record of treatments and other milestones, a PSA graphing function and a regular check-up that records self-reported ratings across 5 quality of life domains and graphs these over time. PROSTMATE also offers telehealth (web-enabled video) consultations with prostate cancer nurses and allied health clinicians.

A complex and dynamic algorithm has been designed to tailor the extensive library of information to match the user type and stage of treatment for each person using PROSTMATE. Recommended library information is delivered to the user via their private dashboard and this information automatically updates when information has been read. This aspect of PROSTMATE was designed to help prostate cancer patients navigate to the information most relevant to them and their circumstances, and to reduce the often overwhelming feeling of information overload.

The timeline provides an opportunity for patients to record all their prostate cancer milestones including their treatments, test results, medical appointments, personal journal entries and more. The timeline’s graphical illustration of PSA results and self-reported quality of life over time also allows users to keep track of things as simply as possible.

The telehealth consultations are one of the most exciting aspects of PROSTMATE as they connect men, and their families with expert prostate cancer nurses and psychologists (and hopefully in the future exercise physiologists and physiotherapists) whom they may not have had access to in their routine care. We know that many men, particularly men from rural and remote areas, find it very difficult to access allied health services and we hope that delivering clinical consultations via telehealth will facilitate improved access to services as well as overall improvements in quality of life in the long-term; not to mention the potential savings made through reduced travel time, time off work and reductions in patient loads in busy outpatient clinics.

PROSTMATE launched to the general public in November 2013 and since then has attracted more than 700 new members. We have received overwhelming feedback supporting the use of technology in the care of everyone affected by prostate cancer. It’s surprising how many men and family members feel isolated by the traditional medical model and we are delighted that we can harness the power of technology to empower and connect people to their health and wellbeing.

PROSTMATE is free to join and has been supported by generous philanthropic funding. Our program is continually evolving as we learn what is most useful to our members, and through this, we intend to expand and develop new components and functionality in the near future. You can become a member yourself by selecting health professional in the sign up pages to see what PROSTMATE might offer your patients.

Visit www.PROSTMATE.org.au and follow us on Twitter @PROSTMATE

Dr. Addie Wootten
Clinical Psychologist

eHealth Research Manager
Australian Prostate Cancer Research
Twitter: @addiewootten @PROSTMATE

 

Not So Watchful Waiting?

SPCG-4 of Robotic Prostatectomy versus WW: April #urojc summary

This month’s twitter based international urology journal club, found by using #urojc, kicked off with the highly anticipated 20 year follow-up of the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4). This article had twitter buzzing in mid-March when it was published in the New England Journal of Medicine making it an ideal article for April’s journal club. This paper became an instant urology “classic.”

Bill-Axelson et al. published this 18 year follow up of a randomized control trial which separated individuals with early prostate cancer into two groups: watchful waiting or radical prostatectomy. Notable results of the study included a relative risk reduction of 44% from prostate cancer for those who underwent a radical prostatectomy compared to with watchful waiting with the NNT = 8, decreased use of androgen-deprivation therapy in this group, and the benefit of surgery being the most prominent in men <65 years with a 55% decrease in the relative risk of death due to prostate cancer.

Given that these results contradict the well known results of the Prostate Cancer Intervention versus Observation Trial (PIVOT), which started after the advent of PSA screening – the discussion of this article was particularly interesting. They are however, very different studies in terms of era and the populations studied.

During the 48 hour discussion period, key topics discussed were:

  • The applicability of these findings given the many advances in prostate cancer screening, diagnosis, and treatment since the 1990’s
  • The factors that influence the NNT
  • The impact of androgen deprivation therapy within both groups
  • How to weigh the impact of adverse effects including erectile dysfunction and urinary incontinence especially in the context of today’s treatment which includes radiation therapy, an option not addressed in this SPCG-4 study
  • The importance of this study should we face the possibility of shifting back to a pre-PSA era with the new USPSTF recommendations regarding PSA screening

As soon as the discussion opened, a question was posed if this was considered a contemporary cohort:

However, this thought was countered by:

The conversation continued to include the importance of time in NNT as pointed out Stacy Loeb. The point was later made, that the NNT might actually be lower with today’s advents of management in high-risk cancer patients.

There was a brief discussion on the statistic that 60% of the participants in the watchful waiting group underwent ADT treatment versus only 40% in the radical prostatectomy group.

Impact of adverse effects was also briefly discussed. The article stated that 84% of prostatectomy patients had ED versus 80% of the patients in WW.  However, incontinence was only present in 11% of the watchful waiting group versus 40% of the surgery group. These statistics are interesting to compare, when the third option of radiation therapy is introduced. With RT being a viable alternative today compared to the 1990’s when the initial enrollment for the SPCG-4 study was done, weighing the risk/benefits of treatment becomes much more complicated.

The importance of weighing QOL was not forgotten during this discussion.

Finally, there was some great conversation alluding to the relevance of this study in the future given the new guidelines of the USTPSF which recommend against using PSA to screen for prostate cancer in healthy men of all ages on the account that there is no realized benefit.

Overall the importance of this study can be easily summarized as follows:

We welcomed a new member!

A huge thank you to the American Urological Association who supported the Best Tweet prize of a video box set. The winner is Fardod O’Kelly for the following tweet:

Thank you to everyone who joined the discussion. We look forward to seeing you at the May #urojc! 

Meena Davuluri is a 3rd year medical student at Upstate Medical University in Syracuse, NY. She is interested in pursuing a career in Urology. Her interests include cost-effective decision analysis and health policy regarding healthcare delivery models. Follow her on Twitter @MeenaDavuluri.

 

Another good week for radical prostatectomy

The SPCG-4 (Bill-Axelson) study updated again in NEJM

In this week’s edition of the NEJM, Anna Bill-Axelson and the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) investigators have written an impressive update to their famous study comparing radical prostatectomy (RP) to watchful waiting (WW) in a setting of mostly clinically detected prostate cancer. In 2002, the group reported in NEJM at a median 8 years of follow-up that RP reduces disease specific mortality, overall mortality, and risk of metastasis and local progression. The declines in prostate cancer specific mortality were 8.6% for RP versus 14.4% for WW. In 2011, they published again with a median 12.8 years of follow-up and the differences were 14.6% versus 20.7%, but the benefit was impressively driven by men under age 65. Now in 2014, the median follow-up time is 13.4 years with up to 23.2 years at the high end, and overall 64% of the cohort has died by end of 2012 — specific to prostate cancer in 17.7% vs. 28.7%. The number needed to treat is 8. 

What stands out in the latest edition of this famous trial? Although previous reports describe differences in metastatic and progressive disease in WW, this report nicely shows that RP reduces metastatic disease burden, androgen deprivation therapy, and palliative treatments across all age groups — even if mortality comparisons are still more notable in younger cohorts. So the paper has evolved into a key lesson in the natural history of prostate cancer and localized curative intervention (side debate — this paper is not really about radical prostatectomy itself, but rather intervention, and I would assume many similar benefits possible with radiation approaches). Prostate cancer outcomes are more complex than simple cure fractions. Patients can suffer from relapsed disease, multiple treatments, long-term androgen deprivation, and, yes, actual prostate cancer mortality that apparently takes a committee of experts to decipher from competing sources. I think the impact of the study will be that healthy men between the ages of 65-75 may benefit from treatment of lethal potential prostate cancer — but perhaps as measured by endpoints other than mortality. This is especially relevant with the evolving library of treatment options for castrate resistant prostate cancer — it may take a lot longer to actually die of prostate cancer, but who really wants to spend their last 5-10 years of life heavily medicated compared to a more effective localized intervention at an earlier time? Between earlier versions of this study and the PIVOT trial, I think we already believe in the benefits of curative therapy for men <65 years with intermediate to high-risk disease. On the other end of the spectrum, the paper still supports the concept of active surveillance for low risk cancer, although more is to be learned from other accruing cohorts of patients who will undergo selective delayed intervention. 

Overall, I found this to be a highly citable paper with a new set of figures destined for use in many PowerPoint talks to come. The overall message is that RP at the right time and right patient can prevent mortality and disease progression. A comprehensive prostate cancer program should start with such biology-based discussions with patients and then carefully integrate active surveillance in the lower risk end and clinical trials of combination therapy at the higher end. Finally, I wonder if the findings of reduced metastatic events in older patients might re-challenge the screening guidelines that are encouraging less screening after age 70?

John W. Davis, MD
Associate Editor, BJUI

Read the NEJM article

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
 

Article of the month: Targeting the androgen receptor

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 video of a lecture from Professor David Neal, filmed at the Society of Academic Research and Surgery: 2013 Annual Meeting.

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

The transcriptional programme of the androgen receptor (AR) in prostate cancer

Alastair D. Lamb, Charlie E. Massie and David E. Neal

Cambridge University Department of Urology, Addenbrooke’s Hospital and Cancer Research UK (CRUK) Cambridge Institute, Cambridge, UK

Read the full article
ABSTRACT

• The androgen receptor (AR) is essential for normal prostate and prostate cancer cell growth.

• AR transcriptional activity is almost always maintained even in hormone relapsed prostate cancer (HRPC) in the absence of normal levels of circulating testosterone.

• Current molecular techniques, such as chromatin-immunoprecipitation sequencing (ChIP-seq), have permitted identification of direct AR-binding sites in cell lines and human tissue with a distinct coordinate network evident in HRPC.

• The effectiveness of novel agents, such as abiraterone acetate (suppresses adrenal androgens) or enzalutamide (MDV3100, potent AR antagonist), in treating advanced prostate cancer underlines the on-going critical role of the AR throughout all stages of the disease.

• Persistent AR activity in advanced disease regulates cell cycle activity, steroid biosynthesis and anabolic metabolism in conjunction with regulatory co-factors, such as the E2F family, c-Myc and signal transducer and activator of transcription (STAT) transcription factors. Further treatment approaches must target these other factors.

LINK TO VIDEO

Lecture filmed at the Society of Academic Research and Surgery: 2013 Annual Meeting. Video available from The Royal Society of Medicine https://www.rsmvideos.com/videoPlayer/?vid=340

 

Read Previous Articles of the Week

 

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.

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