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In the introduction to their manuscript in this issue of the BJUI, Meeks et al. outline a significant challenge for physicians managing prostate cancer: from the estimated 240 000 diagnosed annually (USA) to the 120 000 choosing radiation, to the 40 000 estimated biochemical failures in the first 5 years who may benefit from additional local therapy to avoid local and/or systemic progression. The basis of these calculations was from conventional beam radiation, and although we expect dose-escalation strategies to perform better, the ideal management strategy remains to be identified. Indeed, Zelefsky et al. showed that there was a higher risk of metastatic disease with external beam radiation therapy than with surgery for high-risk prostate cancer, although there was some confounding of the results due to the differences in salvage treatment. This confounding may be the key point: more acceptable salvage options may promote optimal local control and fewer progressions.
Certainly, the concern with salvage therapy after failed radiation is the toxicity, and the concept of achieving less urinary incontinence with cryotherapy or even focal cyrotherapy is attractive, as outlined by de Castro Abreu et al. in this issue. In their parallel cohorts of total and focal salvage cryotherapy, urinary incontinence occurred in three (13%) of the 25 salvage total and zero of the 25 salvage focal therapies, and there was only one fistula in either series. However, the cancer control outcomes are different among these non-randomised and non-comparable cohorts: 87% disease-free survival for patients with bilateral disease treated with total cryotherapy and 54% disease-free survival for patients with unilateral disease treated with focal cryotherapy. These comparisons are limited, but one could hypothesise that salvage total therapy has improved disease control over salvage focal therapy.
Returning to the Meeks et al. study, a cohort of 198 patients with biopsy confirmed radiation recurrence underwent a salvage prostatectomy at a single institution. Pre-treatment biopsies showed 48% and 13% Gleason sums 7 and 8–10, respectively, and multifocal location in 61% (92/151 patients). Salvage prostatectomies showed 56% advanced pathological stage and 35% Gleason 8–10, and multifocal location in 57%. In comparing specific biopsy locations to radical prostatectomy mapping, undetected cancers from biopsy ranged from 12% to 26%, and 58% upgrading. In patients with unilaterally localised biopsies, final pathology was unilateral in only half – a statistic that matches the PSA failure rate from focal therapy in the de Castro Abreu et al.’s study. The authors point to a non-radiated biopsy-to-prostatectomy study and by comparison conclude that the accuracy of biopsy in radiated prostates is actually greater, perhaps due to the smaller radiated gland. But let’s be clear – both groups had significant rates of multifocal disease and inaccuracies between biopsy and radical prostatectomy.
These two BJUI studies provide a developing agenda of what we know and do not know about salvage therapy for failed radiation:
John W. Davis and Seungtaek Choi*
Departments of Urology and *Radiation Oncology, UT MD Anderson Cancer Center, Houston, TX, USA
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Advances in minimally invasive endourological techniques continue to provide the Urologist a myriad of options for the management of symptomatic renal calculi. Previously, shock wave lithotripsy (SWL) or standard percutaneous nephrolithotomy (PNL) were the only two endourological options available. Yet, limitations of these two ‘standard’ techniques result from hard or dependent stones (for SWL) or the potential of increased morbidity during the treatment of small renal calculi (for PNL). Now the introduction of smaller fibre-optic needle-scopes combined with laser stone fragmentation (micro-PNL or ‘microperc’) provides access to difficult-to-reach renal calculi with minimal patient morbidity. Moreover, newer flexible ureteroscopes, along with nitinol baskets and graspers (retrograde intra-renal surgery or ‘RIRS’) allow another minimally invasive option for hard-to-reach renal calculi.
In the present issue of BJUI, Sabnis et al. present a well performed, randomised, prospective trial comparing microperc to RIRS for the management of renal calculi of <1.5 cm in diameter. They determined that both procedures were essentially identical in their ability to remove small-to-moderate sized renal stones with minimal patient morbidity/complications. Yet, both of these procedures have inherent limitations that are unique to the instrumentation used for each technique. Microperc has limited applicability for stones located anteriorly within the kidney, while RIRS is an ideal technique to access symptomatic renal stones within an anterior calyx. RIRS may not be able to target lower pole calculi in those patients with an acute infundibular angle or stones in a calyceal diverticulum, whereas a microperc can be used to reach hard-to-access calculi.
One must accept that both of these innovative procedures are inefficient in their ability for removal of large volume stones and neither technique offers an efficient method of clearing multiple stone fragments. Ideally, both microperc and RIRS should only be used for small volume renal calculi.
I would offer that both procedures are safe and effective alternatives for the management of small renal calculi. Yet, we must be realistic in offering these techniques to our patients, pairing each procedure with the most appropriate situation. Even in 2013, large volume renal calculi are best managed by standard or mini-PNL, where devices such as ultrasonic lithotripsy or dual ultrasonic/pneumatic lithotripsy offer efficient methods of stone removal. SWL is still a reasonable option for the treatment of renal calculi of ≤1 cm in diameter.
Now RIRS and microperc can be added to the list of treatment options for managing symptomatic renal calculi. In patients with large renal calculi, along with multiple medical comorbidities or bleeding diatheses/on anti-coagulation, RIRS provides another, yet inefficient, alternative for stone removal, often requiring multiple procedures to clear the stone. In those situations where the flexible ureteroscope cannot target a renal calculus of <1.5 cm, microperc provides the option of accessing the calculus, yet offers no method of efficiently clearing stone fragments. If we set reasonable expectations for the use of these two minimally invasive endourological techniques, our patients will surely benefit.
Glenn M. Preminger
Duke University Medical Center, Durham, NC, USA
Melbourne played host to the Prostate Cancer World Congress last week. With over 1,000 delegates and a stellar International faculty comprising of 21 global leaders, it was no surprise that tweeters worldwide battled off sleep to keep up with the action.
Amidst a buzzing crowd, overlooking the iconic @MCG #pcwc13 President Tony Costello reminisced about the very first conference; 2 speakers, 27 delegates made up largely of residents only fourteen years ago. Undoubtedly the highlight of the conference was the release of ‘The Melbourne Consensus Statement on Prostate Cancer Testing’. This gathering of worldwide experts allowed for the ideal opportunity to generate a set of consensus statements with the goal of finally ending the confusion that exists with current guidelines and allow for early detection of prostate cancer.
As well as major media coverage following the statements release #PCWC13 caused a stir virally around the globe. With tweeters from New Zealand, United Kingdom, Ireland, United States, Canada and all states and territories of Australia the success of #SoMe was a hot topic of discussion around the Convention Centre. Novel and newbie #SoMe users could not resist joining the frenzy of twitter traffic which grew in strength over the five days.
Dr Stacy Loeb kickstarts #PCWC live on @abc
The conference featured three main streams; Clinical Urology #CU, Translational Science #TS and Nurses & Allied Health #NAH, a programme which ensured the multidisciplinary team and all practitioners involved in prostate cancer care could learn and share expertise. Day 1 the tone was set at the moderated poster presentations by @DrHWoo who outlined some conference housekeeping rules ‘All phones on silent and everyone must be adequately tweeting!!’.
An exceptionally high standard of candidates left decision making difficult for poster judges; @DrDanielMoon and @DrHWoo. A clever addition to the #PCWC13 welcome package was the BJUI supplement containing all #CU abstracts, allowing delegates and faculty to gain further knowledge of each individual presentation.
That evening @AustProstate The Australian Prostate Cancer Research function and drinks allowed faculty to relax and mingle while receiving a warm welcome from Professor Rosemary Knight from the Dept. of Health, Canberra, Hon David Davis MP, Victorian Minister for Health and Hon Dr Andrew Southcott, Federal Shadow Spokesman for Health.
On Wednesday morning at the opening multidisciplinary plenary @SwannyQLD the Honourable Wayne Swan MP gave an emotional account of his personal battle with prostate cancer. His heartfelt story touched all those present, emphasising that underlying the scientific and clinical excellence of a conference of this magnitude remains the care of our patients.
@LoebStacy Assistant Professor of Urology and Population Health from NYU followed with a superb summation of ‘Practice-changing publications in prostate cancer this year’. Dr Loeb condensed a typically three hour session by herself and Dr. William J. Catalona into twenty minutes addressing the most prominent issues in prostate cancer, including ‘Nature V Nurture’, the fish oil debate, the FDA approval of Radium-223 and the PSA recommendations by USPSTF.
Prof Noel Clarke from the Christie Hospital in Manchester presented the inaugural BJUI Lecture “Breaking the Mould in Prostate Cancer Trials”, to a packed audience including clinicians and scientists.
On his fourth trip to Australia and attending the conference, Dr. Patrick C Walsh delivered the inaugural speech so named after the orator himself, a lecture which will continue to be an annual highlight of the APCC. An insightful look at the progress in prostate cancer genetics, over the last two decades, from one of the fathers of Urology kickstarted #PCWC13.
#PCWC13 co- convenor A/Prof Declan Murphy released ‘The Melbourne Consensus statement ‘at 1pm sparking major national and global media attention.
The signatories outlined five major points with a view to clarifying the use of PSA testing and media representatives were given the chance to address pressing questions with @LoebStacy, @proftcostello, Dr. Walsh, Dr Catalona and Mr Murphy (@declangmurphy) at the press conference.
https://www.couriermail.com.au/lifestyle/health-fitness/prostate-cancer-test-should-be-taken-by-men-in-their-40s/story-fnihoylo-1226692750214
https://www.news.com.au/lifestyle/health-fitness/prostate-cancer-test-should-be-taken-by-men-in-their-40s/story-fneuzlbd-1226692750214
https://www.theaustralian.com.au/news/breaking-news/prostate-experts-end-psa-test-confusion/story-fn3dxiwe-1226692802245
https://au.news.yahoo.com/thewest/a/-/newshome/18405046/debate-reignites-on-prostate-screening/
https://www.medicalobserver.com.au/news/international-experts-support-psa-testing
https://www.bloomberg.com/news/2013-08-07/prostate-test-warrants-rational-use-doctors-say.html
https://localtoday.com.au/get-local/news/88156-prostate-experts-end-psa-test-confusion.html
Lat
e morning and afternoon on Wednesday was filled with an extensive range of sessions in all three streams, including discussion and developments on tumour imaging, therapies & biomarkers and management of sexual rehabilitation. A round table discussion on PSA testing and the ‘Melbourne Consensus Statement’ caused some heated debate with controversial questions from the audience. Cocktails in the exhibition centre followed, where delegates were given the opportunity to mingle with faculty and further discuss the monumental statement which has undoubtedly put Melbourne and Victoria on the map as a centre of Urological academia. Pharmaceutical and surgical sponsors showcased their latest innovations and enthusiasts were given the chance to practise skills robotic on the Da Vinci console. An eventful day drew to a close @MCEC with the announcement of the poster winners, generously sponsored by Ipsen Pharmaceuticals.
#CU- Survival disparities between Maoiri and non-Maoiri men with non-localised prostate cancer in New Zealand. Zuzana Obertova
#NAH-New prostate cancer diagnoses-improving timeliness of communication with patients General Practitioners. Sue Stanbridge
#TS-Engineering a High-Throughout Prostate Cancer Stem Cell Niche Mimic. Micael Doran
The BJUI were major supporters of this year’s PCWC and published all of the accepted abstracts in a special supplement (https://onlinelibrary.wiley.com/doi/10.1111/bju.2013.112.issue-s1/issuetoc)
Thursday flew into action bright and early with breakfast talks from Dr. Joseph Smith, Professor Paul Waring and an expert #NAH panel. A combined multidisciplinary plenary addressed risk stratification and imaging, with notable speakers including Dr Matt Cooperberg on the issues in treating localised prostate cancer and Dr Tom Aherling ‘The critical role of hypogonadism or low testosterone in prostate cancer’. Key topics addressed in sessions on Thursday included active surveillance, changes in treatment of options of metastatic prostate cancer and screening. Highlights included an excellent lecture on Radium 223 by Dr. Oliver Sartor, an anecdotal insight into the recent work of Dr. Niall Clarke and Dr. Monique Roobol addressed ‘The 
PRIAS project’. For those delegates that had thus far escaped the #SoMe excitement, a workshop to twitter with the times was provided and the evening closed with an extensive global perspective on prostate cancer.
An academic programme and faculty line-up that would surely struggle to be matched, was further enhanced by the splendour and uniqueness of Thursday evenings congress dinner. Guests enjoyed pre-dinner drinks and canapés while exploring the National Sports Museum before being treated with the rare honour of stepping out onto the ‘hallowed turf’ of the mighty MCG. As if we had not been 
spoiled enough, the Aussie experience continued upon entering the Members dining room where we got the chance to cuddle a Koala, pose with crocs and if one dared; to dangle a python around your neck! It had both young and more mature delegates jumping around like children. The magnificence of the location was conveyed further to guests by a fun fact quiz on @MCG. Main course was an Australian culinary delight, with accompanying national wines and a surreal view of Australia’s most spectacular sporting venue. Mark Holden had guests laughing while Catarina Torres ensured faculty and delegates of all ages put on their #dancingshoes.
Masterclasses on Friday in robotic-assisted surgery remains one of the most favoured aspects of the program with surgeons of all levels looking forward to hearing tips and techniques from #robotics worldwide leaders. The da Vinci Prostatectomy Masterclass was conveend by Dr Daniel Moon and Dr Geoff Coughlin. Key speakers included Dr Tom Aherling and Dr David Gillatt, between whom have experience of over 15,000 radical prostatectomies. Dr Aherling talked through a full length RARP case sharing advanced tricks, followed by Dr. James Borin’s discussion on the intricacies of UV anastomosis. Trainees enjoyed a more intimate opportunity to engage with experts such as @LoebStacy, @dr_coops, @JGrummet, @DrDanielMoon, @lawrentschuck in a master class engineered for budding future urologists. Knock off drinks took place that evening on the glistening Southbank as the success of #PCWC13 could hardly be disputed. A sunny Melbourne Saturday saw GPs provide a workshop for GPs to improve both their knowledge and management of men with prostate cancer both in terms of testing and treatment.
By the end of the week, data from symplur.com using the #pcwc13 hashtag showed just how imapct this year’s Congress had on social media.
The BJUI Social Media team were very pleased to be a part of this success.
It was my first Urology conference and as a medical student I was excited to have an opportunity to be in the same centre as such a stellar line-up of experts. In all honesty I was star-struck. As a member of the BJUI social media team I was tweeting until my thumbs ached but not only did this allow me to engage with @urotwitteraiti household names virally, in many cases it gave me a window to engage with them in person. #Surreal. A fact that surely emphasises the power of #SoMe and would quash any reservations of #tweeterdoubters.
#pcwc13 #RoaringSuccess
Follow the link to Australian Prostate Cancer Research to see highlights of all the action. https://www.facebook.com/media/set/?set=a.503695969711643.1073741827.232024796878763&type=1
Authors:
The BJUI Social Media Team at PCWC – Áine Goggins, Medical Student, Queens University Belfast and University of Melbourne; Dr Marni Basto, Peter MAccAllum Cancer Centre, Melbourne; Dr Sarah Wilkinson, Monash University, Melbourne.
@gogsains @DrMarniqueB @wilko3040
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The recently published Viewpoint of the National Cancer Institute working group on “Overdiagnosis and Overtreatment in Cancer” by Esserman and colleagues [1] raises continued discussion as to whether some lesions currently classified as carcinomas should have the designation of “cancer” removed, based on low rates of progression, death, and other adverse outcomes. Pertinent to those interested in urology, a central example in the article is prostatic adenocarcinoma.
One simple answer to this question is that to a small extent, a subgroup of prostatic lesions has already been reclassified as not cancer: In current practice, needle biopsy or radical prostatectomy specimens with an overall Gleason score (GS) of 5 or less are now quite rare in current practice. This shift is due in part to modern updates to the Gleason grading system [2], under which many tumors now reach thresholds for GS6 or above. However, at least some lesions previously considered adenocarcinoma with a low overall GS would now be categorized as atypical adenomatous hyperplasia or adenosis in the era of immunohistochemistry for markers of prostatic basal cells. Nonetheless, the current and more controversial debate surrounds whether some (or all?) tumors currently classified as GS6 could be recategorized as not “cancer”.
Arguments against removing the cancer designation from some prostatic adenocarcinomas:
A major difficulty from the pathologic standpoint in adopting a non-cancer nomenclature for some tumors (such as GS6 adenocarcinomas) is that the Gleason pattern 3 component of a GS 3+3=6 tumor (small, round prostatic glands that lack a basal cell layer and infiltrate between benign glands) is for all intents and purposes identical to the Gleason pattern 3 component of a GS 3+4=7 or higher prostate cancer. These similarities are not limited exclusively to the microscopic appearance but also include a number of immunohistochemical and molecular features, as summarized in a recent article addressing this question [3]. Therefore, no pathologic features are as yet defined that ideally predict whether Gleason pattern 3 glands in a biopsy specimen represent a pure GS6 tumor or a component of higher-grade tumor in which the high-grade component is not represented. Not surprisingly, it is not unusual for tumors with GS6 on needle biopsy to be upgraded to GS7 at radical prostatectomy [3], particularly when a high tumor volume is present in the needle biopsy.
Gleason pattern 3 glands from a GS7 tumor, identical to those of a GS6 tumor.
To compare to other cancers with low risk of aggressive behavior, basal cell carcinoma and squamous cell carcinoma of the skin similarly show locally infiltrative properties, supporting their classification as carcinomas by a classical pathologic definition. Despite that the word “carcinoma” continues to be used for these tumors, most patients are not concerned that they have a life-threatening disease and these lesions are even excluded from the American Cancer Society statistics regarding cancers [4]. In the same way, Gleason pattern 3 glands exhibit infiltrative growth by extending between benign glands, invading nerves, and sometimes extending outside of the prostate. This difference in mindset regarding some types of “cancers” could be considered supportive evidence for the assertion in the recent Melbourne Consensus Statement that uncoupling prostate cancer diagnosis from intervention may be more appropriate than removing its “cancer” nomenclature.
This small GS6 adenocarcinoma was an incidental finding in a radical cystoprostatectomy specimen for bladder cancer but surprisingly extended into periprostatic fat via this focus of perineural invasion.
Supporting removal of the cancer designation from some prostatic adenocarcinomas:
A valid argument of the NCI Viewpoint is that a neoplasm should have a substantive rate of progression and patient death if it is to be considered a cancer. Likewise, others have questioned whether low-volume GS6 tumors fulfill other molecular and pathogenetic hallmarks of cancer, such as unlimited replicative potential and other features [5].
In general, benign and malignant neoplasms can be regarded as having some prototypical gross and microscopic pathologic characteristics, such as a circumscribed vs infiltrative growth and homogeneous vs pleomorphic cell population. However, differentiating benign from malignant lesions also relies heavily on parameters specific to the organ involved. Clear cell renal cell carcinoma, another genitourinary tract tumor, often does not possess these prototypical features of malignancy. Tumors often form a well-circumscribed mass without an “invasive” growth pattern and they often are composed of a uniform population of cells. However, based on known behavior of these tumors, their status as a malignancy is not in doubt. Conversely, renal oncocytoma is a benign neoplasm that shares some of these general features (a round mass composed of a homogeneous population of renal tubular cells). Occasionally oncocytomas appear infiltrative by extending into the perinephric fat or renal vein, yet their status as benign is also not the subject of debate. If some prostate cancers do not have a substantial likelihood of resulting in progression and death, they may not meet an important criterion for a diagnosis of cancer, despite that other features, such as infiltration of tissues, invasion of nerves, and loss of the basal cell layer are characteristic of a malignant neoplasm.
Since a diagnosis of GS6 by needle biopsy is not always predictive of a radical prostatectomy overall GS6, a major challenge to such an approach would be to determine where such a cutoff could be drawn between “cancer” and “not cancer” [5]. If based on tumor volume, it would be difficult to conceptualize that a small amount of GS6 glands would be regarded as a benign lesion, whereas a large amount of identical glands would represent a malignant lesion. Alternatively, the presence of Gleason pattern 4 could used as the point of differentiation (GS7 or above). In the endometrium, a disorganized proliferation of crowded glands with some cytologic features of cancer is regarded as complex atypical hyperplasia. Diagnosis of adenocarcinoma is then reserved for proliferations with a confluent growth of these glands, similar to the threshold for recognizing a component of cribriform glands as Gleason pattern 4. A limitation to such an approach, however, is that a substantial fraction of patients with a needle biopsy GS6 are upgraded to GS7 at radical prostatectomy, as discussed above. Likewise, the ability to treat and monitor GS6 adenocarcinoma nonsurgically is not quite analogous to that of endometrial hyperplasia.
Higher magnification of image 2 shows Gleason pattern 3 glands invading a nerve with ganglion cells.
Other points of discussion
The NCI Viewpoint also suggests that high-grade prostatic intraepithelial neoplasia (HGPIN) no longer be considered cancer or even neoplasia. A comparison to ductal carcinoma in situ (DCIS) of the breast for this argument is somewhat flawed, as HGPIN neither contains the word “carcinoma” nor is justification for treatment in and of itself. Its status as a risk factor for a future cancer even remains debated. The proposal to remove “neoplasia” from HGPIN is also a confusing one, particularly as cervical cancer is noted as an example of the successful application of screening, in which “cervical intraepithelial neoplasia” is the preferred term for precancerous lesions. The authors suggest the designation “indolent lesions of epithelial origin” (IDLE) for cancers in this category to convey their low likelihood of aggressive behavior. However, would recognizing the status of these lesions as at least premalignant neoplasms be more appropriate?
Likely a typographical error in the Viewpoint is that the authors also cite reclassification of urothelial papilloma as papillary urothelial neoplasm of low malignant potential [1]. Since urothelial papilloma has never been considered a malignant neoplasm, the authors likely meant reclassifying “grade 1 urothelial carcinoma” to papillary urothelial neoplasm of low malignant potential.
References
[1] Esserman LJ, Thompson IM, Reid B. Overdiagnosis and Overtreatment in Cancer: An Opportunity for Improvement. JAMA. 2013 Jul 29:
[2] Epstein JI, Allsbrook WC, Jr., Amin MB, Egevad LL. The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. Am J Surg Pathol. 2005 Sep: 29:1228-42
[3] Carter HB, Partin AW, Walsh PC, et al. Gleason score 6 adenocarcinoma: should it be labeled as cancer? J Clin Oncol. 2012 Dec 10: 30:4294-6
[4] Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013 Jan: 63:11-30
[5] Ahmed HU, Arya M, Freeman A, Emberton M. Do low-grade and low-volume prostate cancers bear the hallmarks of malignancy? Lancet Oncol. 2012 Nov: 13:e509-17
Sean Williamson is Senior Staff Pathologist in the Department of Pathology and Laboratory Medicine, Henry Ford Health System, Detroit MI, USA. @Williamson_SR
In this issue of BJUI, Ficarra et al. present the long-term (mean 81.3 months) follow-up of a case series of 183 men that underwent robot-assisted radical prostatectomy (RARP) at a single academic medical centre in Europe. To the authors’ credit, they report both cancer control and patient-reported outcomes, using well-known validated and reliable instruments to assess both urinary and sexual function. Like others before them, Ficarra et al. demonstrate that RARP is a safe and effective way to treat localised prostate cancer.
However, the question the study raises is not so much about the operation’s success rate but rather how success is defined in the first place. Throughout the prostate cancer literature, we have loosened definitions of successful urinary and sexual function to make RP more palatable to patients. In the present study, potency is effectively defined as a Sexual Health Inventory for Men (SHIM) score of >17 with or without the use of a phosphodiesterase type 5 (PDE5) inhibitor. Similarly, continence is defined as either no pad use or the use of a single pad ‘for security’. This approach certainly has face validity to us as clinicians. After all, PDE5 inhibitors are effective therapies for erectile dysfunction and the use of a single urinary liner certainly does not seem like a big deal. However, we need to consider this from the patient’s perspective. Both urinary pads and PDE5 inhibitors are costly to the patient and may represent an inconvenience and a potential embarrassment to many men. Is it really fair to tell men that they will be potent and/or continent after the operation, if they are going to require these additional interventions to achieve the desired state? I think not.
Going forward, we must set the bar higher if we are to be truly honest with our patients and optimise outcomes after RP. We must effectively ‘leave patients the way we found them’ with the critical difference being that they are now cancer-free. In other words, if a man was able to achieve an erection sufficient for intercourse preoperatively without the use of PDE5 inhibitors, he should only be considered potent postoperatively if he is in the same state, i.e. able to achieve an erection sufficient for intercourse without the use of a PDE5 inhibitor. The same holds true for urinary continence and the use of urinary liners. This will certainly make it more difficult to achieve the ‘trifecta’ but the reader should remember that the term is meant to imply ‘triple perfection’ and needing to use a PD5 inhibitor for sexual activity or having to wear a urinary pad, while acceptable to many patients, is certainly not perfect.
Some will say that I am insisting that the bar be set too high, that patients are willing to accept these reasonable but less than perfect definitions of success to be cured of their cancer. I acknowledge that there may be some validity to this argument in men with higher risk disease, where we know that cancer control and cure is necessary. However, I do not think the argument holds up in the case of men with low-risk disease, many of whom will never experience any symptoms of prostate cancer in their lifetimes and will not die of their disease if it were left untreated. In these patients, setting the bar higher would not only be more honest but it would probably increase the uptake of active surveillance and decrease overtreatment. In summary, while the use of more stringent definitions of success after RP may make our operations look ‘worse’, it will help our patients to set more realistic expectations, make more informed choices about treatment and ultimately to have better outcomes.
David F. Penson
Department of Urologic Surgery, Vanderbilt University, 2525 West End Avenue, Suite 1200, Nashville, TN, 37203, USA
Following the recent fish oil and prostate controversy (which BJUI Chairman Dr David Quinlan recently blogged about, the August International Urology Journal Club discussion on Twitter was based on the recent high-profile (and controversial) paper “Plasma Phospholipid Fatty Acids and Prostate cancer risk in the Select trial”, available by advance access from the Journal of the National Cancer Institute, June 10, 2013.
In the recent weeks, many concerned patients had attended urologist and GP clinics, enquiring about the reports that fish oil supplements increase the risk of prostate cancer. This has led to lengthy discussions between patients and their doctors during consultations, and even caused some clinics to run overtime.
So, does fish oil really lubricate prostate cancer growth, or is this all just a fishy tale?
In summary, this case–cohort study set out to examine the association between plasma phospholipid fatty acids and prostate cancer risk among participants in the Selenium and Vitamin E Cancer Prevention Trial. 834 men diagnosed with prostate cancer formed the prostate cancer group. 1393 men chosen at random, and matched according to age and race, formed the non-cancer group. The study reports that men in the lowest quartiles of LCω-3PUFA, compared with men in the highest quartile, had increased risks for low-grade (HR = 1.44, 95% CI = 1.08 to 1.93), high-grade (HR = 1.71, 95% CI = 1.00 to 2.94), and total prostate cancer (HR = 1.43, 95% CI = 1.09 to 1.88). Similar associations were reported for individual long-chain ω-3 fatty acids. Higher linoleic acid (ω-6) was associated with reduced risks of low-grade (HR = 0.75, 95% CI = 0.56 to 0.99) and total prostate cancer (HR = 0.77, 95% CI = 0.59 to 1.01); however, there was no dose response. This study therefore concluded that increased prostate cancer risk among men with high blood concentrations of LCω-3PUFA was confirmed. The authors went on to say that the consistency of these findings suggests that these fatty acids are involved in prostate tumorigenesis, and that recommendations to increase LCω-3PUFA intake should consider these risks.
There has been a lot of media hype surrounding this paper, with the claim that fish oil supplements may increase one’s risk of prostate cancer. This has led to many anxious patients. It is not the first time that sensational claims of natural therapies either causing or preventing cancer has received a lot of media attention.
However, as doctors who have patients and colleagues asking us for sound advice on the matter, it is important that we don’t simply dismiss such hype (and questions from anxious patients) without looking into the matter more deeply, examining the evidence for ourselves, and forming a sensible opinion.
Early in the discussion, the methodology of the study was criticised as being observational by Kate Linton and Faisal Ahmed agreed. The study lacked a proper control group, and did not adequately address confounding factors. Associations were attributed to causation.
Stacy Loeb pointed out that the study did not record the amount of fish oil supplements ingested by any of the men in the study and instead on the basis of a single serum level. Yet the media extrapolates the study’s findings to make recommendations about fish oil supplements, which can be delivered in various formulations and doses.
There was also concern for the assay method used in measuring plasma lipids.
This study’s conclusions might have interesting commercial ramifications. I wonder whether there has been a drop in fish oil supplement sales this week?
However, it is worthwhile to note that there have been other prospective studies and metanalyses that have shown an inverse association between fish oil and prostate cancer. Helen Nicholson brought to our attention, a paper published in Cancer Epidemiology, Biomarkers and Prevention in 2007, which concluded that higher blood levels of long-chain n-3 fatty acids, mainly found in marine foods, and of linoleic acid, mainly found in non-hydrogenated vegetable oils, are associated with a reduced risk of prostate cancer.
To conclude the discussion, several participants stated
My take home message from the August #urojc discussion is;
1.Although interesting, this study is limited by its methodology – it was not a randomised controlled trial of fish oil supplements versus no fish oil supplements. Therefore it cannot answer this question.
2.This study does not provide sufficient evidence to confirm whether omega-3 fatty acids conclusively lead to increased risk of prostate cancer.
3.Media hype = anxious patients. But we can tell our patients the science.
The winner of the best tweet prize for the August #urojc was Kate Linton for the following tweet which highlighted a significant shortcoming of the paper.
The August #urojc prize was kindly supported by the Asian Journal of Andrology.
We thank everyone who participated in the August #urojc, and to the many other on-lookers.
We look forward to your input in the next great International Urology Journal Club discussion, in early September 2013. The topic will soon be announced. If you would like any specific papers to be discussed, please DM us @iurojc – we always welcome your suggestions and feedback.
Dr Amanda Chung is an Australian Urological Surgeon in Training, currently based at The Wollongong Hospital, New South Wales. @AmandaSJChung
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