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Article of the Month: CGa and NSE serum levels as predictors of treatment outcome in patients with mCRPC undergoing abiraterone therapy

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Every Month the Editor-in-Chief selects an Article of the Month 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.

Chromogranin A and neurone-specific enolase serum levels as predictors of treatment outcome in patients with metastatic castration-resistant prostate cancer undergoing abiraterone therapy

Matthias M. Heck*, Markus A. Thaler†, Sebastian C. Schmid*, Anna-Katharina Seitz*, Robert Tauber*, Hubert Kubler*, Tobias Maurer*, Mark Thalgott*, Georgios Hatzichristodoulou*, Michael Hoppner*, Roman Nawroth*, Peter B. Luppa†
,Jurgen E. Gschwend* and Margitta Retz*

 

*Department of Urology, and †Institute of Clinical Chemistry and Pathobiochemistry, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany

 

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Objective

To determine the impact of elevated neuroendocrine serum markers on treatment outcome in patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing treatment with abiraterone in a post-chemotherapy setting.

Patients and Method

Chromogranin A (CGa) and neurone-specific enolase (NSE) were determined in serum drawn before treatment with abiraterone from 45 patients with mCRPC. Outcome measures were overall survival (OS), prostate-specific antigen (PSA) response defined by a PSA level decline of ≥50%, PSA progression-free survival (PSA-PFS), and clinical or radiographic PFS.

jan-2017-aotw1-results

Results

The CGa and NSE serum levels did not correlate (P = 0.6). Patients were stratified in to low- (nine patients), intermediate- (18) or high-risk (18) groups according to elevation of none, one, or both neuroendocrine markers, respectively. The risk groups correlated with decreasing median OS (median OS not reached vs 15.3 vs 6.6 months; P < 0.001), decreasing median clinical or radiographic PFS (8.3 vs 4.4 vs 2.7 months; P = 0.001) and decreasing median PSA-PFS (12.0 vs 3.2 vs 2.7 months; P = 0.012). In multivariate Cox regression analysis the combination of CGa and NSE (≥1 marker positive vs both markers negative) remained significant predictors of OS, clinical or radiographic PFS, and PSA-PFS. We did not observe a correlation with PSA response (63% vs 35% vs 31%; P = 0.2).

Conclusion

Chromogranin A and NSE did not predict PSA response in patients with mCRPC treated with abiraterone. However, we observed a correlation with shorter PSA-PFS, clinical or radiographic PFS, and OS. This might be due to an elevated risk of developing resistance under abiraterone treatment related to neuroendocrine differentiation.

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Editorial: Circulating biomarkers of NEPC – an unmet challenge

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Prostate cancer is a global health issue and, although the overwhelming majority (>95%) of metastatic castration-resistant prostate cancers (CRPCs) have adenocarcinoma histology [1], a subset of tumours acquire histopathological and immunohistochemical evidence of neuroendocrine differentiation, with a variety of morphological classifications being reported [1]. Nonetheless, the term ‘neuroendocrine prostate cancer’ (NEPC) should be reserved for tumours with absent or minimal androgen-signalling modulated transcription [2]. NEPC arising in the castration-resistant scenario (treatment-related NEPC or tNEPC) [2] is a disease of unknown prevalence and without an optimum treatment regime. Autopsy studies have shown at least focal neuroendocrine differentiation may be present in up to 33% of patients [3]. The cellular precursor of tNEPC is still debated, but a common clonal origin from adenocarcinoma CRPC (adeno-CRPC) is likely [2]. The assumption of negligible androgen signalling in these tumours implies resistance to agents such as abiraterone and enzalutamide. In this setting, research focused on identifying biomarkers of tNEPC is to be welcomed.

Heck et al. [4] determined the prognostic impact of elevated circulating neuroendocrine biomarkers chromogranin A (CGA) and neuron-specific enolase (NSE) in the serum of patients with CRPC treated with abiraterone in the post-chemotherapy setting. Although CGA and NSE did not predict PSA response, they correlated with clinical and radiographic progression-free survival (PFS), as well as overall survival (OS). The association between these biomarkers and clinical outcomes in metastatic CRPC has been confirmed in retrospective studies [5]. According to the authors, this association, independently of PSA response, underlines the sub-clonality of this disease, and the key role of androgen receptor (AR) signalling, even in advanced disease [4].

The marker NSE is considered to be generic, with high sensitivity but low specificity; CGA is a more specific neuroendocrine tumour biomarker and a common constituent of neuroendocrine tumour secretory granules. Abnormal CGA levels have, however, been significantly associated with intake of proton pump inhibitors in patients treated with abiraterone for metastatic CRPC rather than with duration of treatment [5]. Unfortunately, the use of proton pump inhibitors in that study was not disclosed and may have affected the reported results. Moreover, compared with previous experience, the rate of abnormal NSE was significant higher, probably in keeping with the low specificity of this biomarker.

Interestingly, the authors report an OS and PFS of 12.7 and 3.7 months, respectively [4]. These data are significantly different from the results of the COU-AA 301 study, in which treatment with abiraterone resulted in improved OS (14.8 vs 10.9 months) [6]. Surprisingly, there was no difference in PFS between abiraterone in the study by Heck et al. and the control arm of the COU-AA 301 trial (3.6 months) [6]. This discordance could be attributable to the small sample size of their study rather than the high PSA level at initiation of abiraterone, as claimed by the authors. In support of this alternative possibility, a post hoc analysis of the AFFIRM trial [7] showed consistent benefits in OS and PFS with second-generation hormonal treatments, regardless of baseline disease severity as assessed by PSA level.

Nevertheless, identifying patients with tNEPC is an urgent clinical need; genomic germline and somatic DNA next-generation sequencing as well as transcriptomic analysis of metastatic biopsies should now be considered a key approach to better understanding the heterogeneity of metastatic CRPC and to personalize treatment in order to maximize benefit.

There is substantial genomic overlap between adeno-CRPCs and tNEPC. TMPRSS2-ERG is the most common genomic aberration in prostate cancer and has been reported in NEPC with a similar frequency [2]. Furthermore, both adeno-CRPCs and tNEPCs are enriched for the inactivation of key tumour suppressor genes, such as RB1 and TP53, compared with hormone-sensitive prostate cancer, albeit in different proportions [2]. Although genomic amplification and activating point mutations of the AR in tNEPCs are notably absent, the presence of AR-splicing variants, including ARv7, is still detectable, suggesting that AR signalling is still present in at least a proportion of tNEPCs [2].

Despite a common background of genomic aberrations, tNEPCs have also been reported to have significant overexpression and copy number gains of AURKA and MYCN (40% of NEPC vs 5% of primary prostate cancer tumours), although these findings remain unsubstantiated [3]. As such, these have been postulated to be drivers of this disease phenotype and are under investigation as targets of novel agents.

Genome-wide DNA methylation analysis has, however, also shown that there are marked epigenetic differences between NEPC and adeno-CRPC, suggesting that epigenetic modifiers play a major role in the induction and maintenance of the neuroendocrine status [2].

In conclusion, the identification and definition of NEPC remains challenging. Blood biomarkers such as NSE and CGA cannot be considered to be proven prognostic biomarkers of NEPC as they have only been evaluated in small retrospective studies not adhering to REMARK criteria [8]. Genomic profiling from tissue biopsies or circulating DNA remains a preferable way to identify NEPC and is increasingly feasible, although still not affordable or a standardized procedure for the definition of NEPC.

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Pasquale Rescigno*,†, Daniel Nava Rodrigues*,† and Johann S. de Bono*,†

 

*Institute of Cancer Research, London, UK and †Royal Marsden NHS Foundatio n Trust, London, UK

 

References

 

1 Epstein JI, Amin MB, Beltran H et al. Proposed morphologic classification of prostate cancer with neuroendocrine differentiation. Am J Surg Pathol 2014; 38: 756–67

 

2 Beltran H, Prandi D, Mosquera JM et al. Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer. Nat Med 2016; 22: 298–305

 

3 Mucci NR, Akdas G, Manely S, Rubin MA. Neuroendocrine expression in metastatic prostate cancer: evaluation of high throughput tissue microarrays to detect heterogeneous protein expression. Hum Pathol 2000; 31: 406–14

 

4 Heck MM, Thaler MA, Schmid SC et al. Chromogranin A and neurone- specific enolase serum levels as predictors of treatment outcome in patients with metastatic castration-resistant prostate cancer undergoing abiraterone therapy. BJU Int. 2017; 119: 30–7

 

5 von Hardenberg J, Schwartz M, Werner T et al. Influence of abiraterone acetate on circulating neuromediators in chemotherapy-naıve castration- resistant prostate cancer. Prostate 2016; 76: 613–9

 

6 de Bono JS, Logothetis CJ, Molina A et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 2011; 364: 1995–2005

 

7 Saad F, de Bono J, Shore N et al. Efficacy outcomes by baseline prostate- specific antigen quartile in the AFFIRM trial. Eur Urol 2015; 67: 223–30

 

8 McShane LM, Altman DG, Sauerbrei W. REporting recommendations for tumour MARKer prognostic studies (REMARK). Br J Cancer 2005; 93: 387–91

 

Surgery or Radiation in Prostate Cancer?

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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

 

Editorial: Robot-assisted radical prostatectomy: getting your ducks in a row!

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Robot-assisted radical prostatectomy (RARP) has become the technique of choice for clinically localised prostate cancer. However, marked inter-surgeon heterogeneity and an obvious lack of standardisation exist for the indications and technique of the procedure. In this issue of the BJUI, Ficarra et al. conducted a multinational survey seeking opinion from 145 robotic surgeons about individual practices during RARP. These opinions can be compared against the benchmark set by the Pasadena Consensus and can help gauge the impact of its recommendations.

Responses from 116 (79.4%) invited surgeons were analysed. The authors acknowledge the limited participation of non-European surgeons (17.1%), which may limit validity and application of its results at a global level. Most surgeons were in consensus with the Pasadena recommendations for transperitoneal access (88%), antegrade approach (76%) and bladder neck preservation (77%). The opinions on cautery use for the seminal vesicle/vas deferens dissection (51% athermal; 21% bipolar), athermal nerve-sparing approach (90%) and the use of the running suture technique for urethrovesical anastomosis (96.6%) were also in agreement.

Despite wide surgeon and institutional variability regarding the definition of bladder neck preservation and its role in the return of urinary continence, most preferred to preserve the bladder neck. This may pose difficulty in the interpretation of the results in view of the ambiguity about the definition and technique adopted under the term ‘bladder neck preservation’ (Eur Urol, BJU Int).

Most of the participating surgeons were using anterolateral prostatic fascia dissection (Veil of Aphrodite) towards preserving the cavernous nerves by using an athermal approach. Over the last decade the evolution of robot-assisted surgery, with excellent three-dimensional visualisation, depth perception, and EndoWrist® technology has made working in the confines of the pelvis both ubiquitous and a desired skill.

The present study found that 33% of surgeons omitted the internal iliac lymph nodes (LNs) and removed only obturator, with or without the external iliac LNs. The Pasadena Consensus recommends a template that includes the internal iliac, external iliac and obturator LNs. Mattei et al. in an attempt to map primary prostatic lymphatic ‘landing’ zones found that after performing a standard limited LN dissection (dorsal to and along the external iliac vein; medially along the obturator nerve) only 38% of LNs were removed. They recommended a template that retrieves LNs extending up to the ureteric crossing of the common iliac vessels. Meanwhile, Menon et al. evaluated the role of only internal iliac LN dissection (limited) in patients with a low probability of nodal disease (Partin table prediction 0–1%), and surprisingly found positive LNs in the internal iliac/obturator region 13.7 times more often than in the external iliac/obturator region. One of the issues that could be addressed in future surveys would be to evaluate how surgeons view and adapt to changes in the proposed LN template. The Pasadena Consensus further recommends considering performing LN dissection for the low-risk category based on the D’Amico risk stratification. The surgeon’s indications for pelvic LN dissection were not addressed in this survey.

Despite significant studies, including two randomised controlled trials (RCTs), published in the peer-reviewed literature reporting minimal advantage for early recovery of urinary continence with posterior reconstruction, a significant number of the surveyed surgeons still preferred to perform it. Responses to other questions about the posterior/anterior reconstruction also showed marked variability reflecting the controversial opinion about the value of these surgical steps.

On the other hand, future surveys should gather opinions about the role of RARP for high-risk disease, standardised evaluation of surgical complications; while addressing continence and potency status along with methods of their measurement. These topics were already addressed in the Pasadena Consensus and obtaining opinions of surgeons will further provide insight as to how surgeons adapt to the ever-changing advances in this field.

Over the last decade RARP has gained acceptance despite the absence of high-quality RCTs in robot-assisted surgery. The Pasadena Consensus was meant to meet the need for uniformity and this study educates us on how the surgeons really perform ‘in the trenches’. Until further evidence is available, surgeon experience and institutional volume will remain the main force driving the use of these surgical techniques and their outcomes.

Ahmed A. Aboumohamed and Khurshid A. Guru
Department of Urology, Roswell Park Cancer Institute, Buffalo, NY, USA

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A Tale of Four Prostates

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There was a time when doctors were reluctant to tell patients the truth about a diagnosis of cancer, and even more unwilling to discuss any illness from which they themselves suffered.  John Anderson broke the mould last year when he made a public announcement about his newly diagnosed liver metastases, which subsequently turned out to be the result of secondary spread of adenocarcinoma of the prostate.

John was President Elect of the British Association of Urological Surgeons (BAUS) at the time, so sadly had to resign his presidency (the best president we never had!) and subsequently his trusteeship of the Prostate Cancer UK charity. John’s energy and drive are legendary, he is a true surgeon’s surgeon. The stoicism and determination that he has displayed throughout a year in which he has received hormonal treatment, followed by chemotherapy, is awe-inspiring.

My admiration for John, in addition to my own recent diagnosis of localised prostate cancer, requiring robot-assisted radical prostatectomy (https://moreintelligentlife.co.uk/content/ideas/simon-garfield/prof-roger-kirby) led me to approach Sean Vesey and Damian Hanbury, whom I knew were similarly afflicted by a disease that carries a 1 in 9 lifetime risk. It occurred to me that there was a great deal to be gained from frank disclosure and discussion, as opposed to treating this problem as some dark, furtive secret. Women suffering from breast cancer are generally much more open about their problem and consequently receive much more support from friends, relatives and others who have been touched by the disease. This empowers them to make the difficult but smarter choices about their health by opting in to breast cancer treatment. Men need this kind of social encouragement and support so that we can be within reach to them as well.

The result was a publication entitled “a Tale of Four Prostates” in the upcoming issue of Trends in Urology and Men’s Health (www.trendsinurology.com) and a short accompanying video.

In this John, Damian and myself discuss the impact of our respective diagnoses and treatment. We sincerely hope that, by being frank, honest and transparent about our own situation, we can help other patients to help themselves by seeking advice and treatment earlier, and by sharing information about their diagnosis with others in order to mobilize support from their family and friends.

 

Sadly, John Anderson has since died. You can read an obituary by Roger Kirby here. 

 

 

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Does Michelangelo’s David have an increased risk of prostate cancer?

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Recently when researching on the Italian Renaissance master Michelangelo and his suffering with kidney stones, I stumbled upon a project on his famous masterpiece David. At the precise time, I was browsing BJUI and came across the article by Motofei et al, on the sexual side effects of finasteride as related to hand preference (right-handed or left-handed) for men undergoing treatment of male pattern baldness. This manuscript reminded me of several articles that measured different parts of the male body and correlated with the risk of prostate cancer. With this paper on my mind and at the same time looking at David, it just occurred to me whether I could predict the possibility him getting prostate cancer!

Let’s start from the beginning. Being born as a male, he had acquired a 1 in 6 chance of being diagnosed with prostate cancer and 1 in 36 chance that he would have died from it. The moment David stood erect as a toddler; the risk of getting prostate cancer became a reality. Indeed, the authors of the study go on to claim the link of erect posture of humans with BPH and infertility. For those interested, the theoretical aspects of erect posture and its effects on the male reproductive tract can be found in this review.

It is worth analyzing the David’s anthropometric measurements and bodily features from head to toe and correlate them to the current available evidence. David’s height has been calculated at being 497 cm. This, in real life would probably make him around 5’ 8” to 6’. According to the findings of the PLCO trial, being tall increased his risk of developing more aggressive prostate cancer and at a younger age. This is supported also by the findings of the ProtecT trial, which demonstrated that for high-grade tumours, there was a 23% increase in risk per 10 cm increase in height. The study group’s meta-analysis of published literature also support the increased risk of prostate cancer with increasing height.

Let us start from his head. Fortunately, David is not bald. Recent evidence suggests a strong correlation between vertex pattern androgenic alopecia and significant risk of prostate cancer. Looking at the elegance of the face, it is quite obvious that he is a clean-shaven man. Fortunately, being white, the age at which he started shaving indicating early or delayed adolescence, does not seem make his chances of getting prostate cancer worse.

Going on to his chest, it is apparent that David did not suffer from Gynaecomastia. There is considerable controversy in the literature regarding the association of gynaecomastia and future risk of prostate cancer. A cohort study following men with histologically proven gynaecomastia did not find any increased risk of prostate cancer but surprisingly showed an increased risk of testicular cancer. David’s chest, abdomen and back lack excess dense body hair. A Japanese study has shown that dense body hair raises the risk of prostate cancer!

A lot of research has gone into determining whether David is a right-handed or a left-handed man. If you take a closer look at the statue, the sling is held by the left hand and a rock on the right, suggesting that he could indeed be left handed, like his creator Michelangelo! Although no specific research has been carried out in prostate cancer, it has been shown in a few studies that women who are left handed are more prone to get breast cancer as compared to those who are right handed. The authors claim the effect of prenatal hormones on the foetus that determines the dominance of the side can also have effects on the breast tissue. A study found that men who were exposed to DES in utero were more likely to be left-handed. Similarly mouse experiments have shown an increased risk of prostate cancer in those exposed to DES. So, there may be a connection between left-handedness and risk of prostate cancer!

Coming to his fingers: The ratio of second to fourth digit length (2D:4D) would allow us to further assess the risk. It is now understood that the 2D:4D ratio is determined by Homeobox (Hox) a and d genes that also regulate urogenital system. What is even more interesting is the study that showed the patients with a lower 2D:4D ratio have higher risks of undergoing prostate biopsy and prostate cancer. The same group indeed went on to prove that a lower digit ratio was related to high percentage core cancer volume and higher Gleason score!

Fortunately, David’s waist circumference (WC) is within reasonable limits, thereby reducing his risk of prostate cancer. A recent study has shown that increased WC seems to be associated with high-grade disease at the time of biopsy.

It is obvious looking at David that he was not circumcised. Although aesthetically pleasing for many, there is considerable debate in the medical as well as philosophical literature whether David was circumcised or not?! Not being circumcised unfortunately increases his risk for prostate cancer.

There is a huge controversy about the size of David’s flaccid penis. Penis size has not (yet) been shown to correlate with risk of prostate cancer. Although, indirectly you conclude that because the 2D:4D digit ratio has been correlated with penis size and as shown above 2D:4D ratio has been correlated with prostate cancer. Therefore, the smaller the penis, greater the risk of prostate cancer! With so many manuscripts being published on 2D:4D ratio, I decided to research more on it and landed up on the Wikipedia page. I was astonished to find the various conclusions that have been reached with the curious case of 2D:4D ratio, including a recent study in Germany that found its correlation with male to female transsexuals!

Although not possible, but of interest would have been to measure David’s anogenital distances from anus to upper penis and from anus to scrotum. A study published in BJUI showed that a higher measurement between the anus and the penis was associated with lower risk of prostate cancer. As you may have guessed, yes there is research going on finding a relationship between anogenital distance and the 2D:4D ratio!

My interest then turned to David’s feet. Looking at it, it does seem that he would have been wearing a shoe size of 10 or 11 at least. Does it matter? Comparing his shoe size and the length of his flaccid penis, I was just reminded of the seminal paper by Jyoti Shah et al, which disproved that shoe size has got to do anything with the size of the penis. However, contrary to this paper, a study confirmed significant evidence of older age at the maximal shoe size (20.1 versus 17.6 years, P <0.05) was associated with increased risk of prostate cancer. Yes, as you may have guessed by now, there is a relationship between the 2D:4D to your penis size!

To conclude on the observations, there are several factors that increased David’s risk and several others that are protective, as shown in Table 1. I would leave it to the reader’s judgment, whether you would recommend a PSA test for David or indeed climb on to him and measure the most important parameter, the 2D:4D ratio!

Amrith Rao is a Consultant Urological Surgeon at Wexham Park Hospital, Wexham, UK. His views are his own. @urorao

 

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On the Receiving End!

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It was weird, having spent a career looking after men with prostate problems, to discover that my own PSA was raised to 4.3ng/mL. A 3 Tesla MRI with gadolinium enhancement revealed a lesion in the right peripheral zone, which a biopsy confirmed as a Gleason 3+4=7 adenocarcinoma. The decision wasn’t difficult for me: I opted for a robot-assisted radical prostatectomy (RARP), to be performed by the Editor-in-Chief of this journal, Professor Prokar Dasgupta, ably assisted by Ben Challacombe and Krishna Patil. Details of my whole journey are available here for those who are interested.

The key point for discussion in this blog is the availability of the latest technology for the care of patients with prostate cancer who are less in the know than me. Shouldn’t we be lobbying for greater access for all to the latest pieces of high tech gear?

3 Tesla MRI imaging, together with the expertise to interpret the findings of diffusion-weighted images, for example, offers the possibility of a “prostate mammogram” which facilitates the targeting of the biopsy and holds the promise of avoiding biopsies in those in whom the MRI images appear blameless.

Da Vinci robotic technology undoubtedly facilitates the surgical procedure, especially the preservation of the neurovascular bundles and the very precise vesico-urethral anastomosis. It certainly was an interesting experience to sit and watch the DVD of my own operation at home, with a catheter still draining my bladder, wondering about my future continence and sexual function, as well as the histopathology report! After an operation like this anybody is going to need assistance to move around the house just to do basic activities like go to the bathroom or even change clothes. That’s why it is very important to check into a nursing home where they offer their professional service. In some cases these nurses don’t work professionally and often neglect their patients needs, so that is why it’s recommended to contact a nursing home neglect attorney for situations like this for legal help.

Am I discombobulated by this experience? Not especially, I genuinely found being on the receiving end of prostate surgery a truly educational experience and I now feel energised to help others get through their journey. In the upcoming issue of Trends in Urology three other of our urological colleagues share their own experiences of prostate cancer, as well as the lessons that can be learned from them. Check out the Trends in Urology website from mid-March onwards.

In the meantime we would be interested in your own thoughts on these issues. Do add a comment or question to this blog.

Roger Kirby
The Prostate Centre, London W1G 8GT

 

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Prostate Cancer Outcomes Study Meets Twitter Face to Face

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The International Urology Journal Club on Twitter discussion for February 2103 was based upon the recently published Prostate Cancer Outcomes Study in the New England Journal of Medicine on 31 January 2013.

The originally planned discussion paper that was only hours away from being announced when it became apparent through Twitter notification by @NEJM that the PCOS paper was going to be published that day. With this news, ‘urology twitter’ spoke loud and clearly (well, tweeted to be technically correct), and it was clear that this paper required our urgent attention.

The primary and senior authors of the PCOS manuscript in Matthew Resnick and David Penson, respectively, were kind enough to commit to making themselves available for the twitter discussion and proved to be valuable contributors.

 

In short, PCOS examined 1655 men who had been diagnosed with prostate cancer in 1994 or 1995, between the ages of 55 and 74 years, and who had either undergone radical prostatectomy (1164 men) or radiotherapy (491 men). Functional status was assessed at ‘baseline’ and at 2, 5 and 15 years after diagnosis. The study found patients undergoing surgery were more likely to have urinary incontinence and erectile dysfunction at 2 and 5 years, but there was no significant difference at 15 years. Patients undergoing surgery were less likely to have bowel urgency at 2 and 5 years, but again, there was no discernible distinction between the two groups at 15 years.

The functional results as stated in the manuscript are poor and this generated discussion that attempted to place these results into context. It was pointed out by Stacey Loeb that with the Massachusetts Male Aging Study (MMAS), 79% of men had ED as defined by IIEF and that there was a concern that, with the present data, the media could interpret it as that all prostate cancer treatments universally cause ED. A later constructive comment was made that if the study had followed matched controls to 15 years, it would allow for meaningful estimation of risk with treatment superimposed on aging.

Discussion shifted to the changes that have occurred over time since men entered the study. A number contributors, including Matt Coward, Rajiv Singal, Quoc Trinh and others commented to the effect that many of the men treated in that era would probably no longer be treated radically and would be managed conservatively. Ben Davies in agreement declared that he would promise never to operate on a man with a Gleason score 2–4 prostate cancer. However, Sean Williamson, Alanna Jacobs and others pointed out that this was not really relevant to the study, which was an examination of functional outcomes.

Is the data applicable to today? In response to Tony Finelli’s tweet of “Why is it that the urologic community always criticizes longterm well designed studies with ’The data are no longer applicable today?’“, Rajiv Singal made a very sobering comment that “Data is very applicable. Study well designed. It’s just that over Tx in many in this group makes side effects more appalling”

Prokar Dasgupta provided some British input with “are patients happier if they are clear of cancer @15 years or would they rather be potent?” Michael Leveridge from Canada provided constructive input with “As rational CaPr treatment shifts toward higher risk (wide fields, less nerve sparing), functional outcomes may actually get worse”

Criticism made that there were many men who missed out on completing their 2 and 5 year questionnaires was responded to by Dave Penson who explained that they were included in the study by using imputed data with a hot deck technique – whilst imperfect, it was the best that they could do to overcome this issue.

Stacey Loeb pointed out that a key strength of the study was that it showed that many short-term differences functional outcomes between RP & RT dissipate over time. From a functional perspective, Tim Averch may have a point when he commented that at 15 years that it may not make any difference as to whether we had performed surgery or radiotherapy.

The question was raised about correlating nerve-sparing surgery and subsequent results. Author Matt Resnick indicated that this was something that was being analysed right now with results forthcoming. On the general issue of improvements in surgery and radiotherapy leading to improved functional outcomes, Matt Resnick indicated that “While tech. improvements in RP and EBRT may incrementally improve outcomes, likely non-differential.” Towards the end of the discussion, it was generally agreed that robotic surgery was the primary manner by which surgery was being performed (at least in the US) and that it was an ‘operative leveler’ in terms of how well surgeons performed a radical prostatectomy.

Helen Nicholson from Australia asked if the late serious effects of radiotherapy were considered and on a similar theme, Matt Cooperberg raised the issue of where only incontinence was reported with regard to urinary function but irritative urinary symptoms were often of greater bother and worse with radiotherapy. Dave Penson responded in that they had data on bother from urinary symptoms and that it was worse at 2 and 5 years for surgery but the same for both radiotherapy and surgery at 15 years.

To complete the round up of the discussion content, the Best Tweet Prize was awarded to Dr Rajiv Singal for the following tweet:-

The Best Tweet Prize was kindly donated by Urology Match.

The above summary only touches upon the discussion, which had 32 participants who made a total of 171 recorded tweets to the hashtag #urojc. This does not include participants and their tweets where the #urojc had been omitted. We had quite a number of new participants this month who were still learning the necessity to include #urojc in all tweets in order for them to be visible to the discussion.

It is also interesting to look at the impact of the Superbowl. The first dip is related to our North American friends signing off to concentrate on the Superbowl and the last dip correlates when the majority of participants are with their heads buried in a robot console/wound or asleep on the other side of the world.

We look forward to seeing your participation in the March #urojc. For further information about what #urojc is all about, see my earlier blog entry on the subject.

 

Henry Woo is an Associate Professor of Surgery at the Sydney Adventist Hospital Clinical School of the University of Sydney in Australia. He has been appointed as the inaugural BJUI CME Editor. He is currently the coordinator of the International Urology Journal Club on Twitter. Follow him on Twitter @DrHWoo

 

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