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Living a life less ordinary

There is a tide in the affairs of men, which, taken at the flood, leads on to fortune; Omitted, all the voyage of their life is bound in shallows and in miseries.Julius Caesar (IV.2) — William Shakespeare (ca.1599)

Wednesday 14 May 2014. A day like any other for the vast majority of those that inhabit this earth, and yet it marked the passing of one of the greats in the world of urology. Few people in the urological fraternity would be unable to recount exactly what they were doing when they heard the news. Prof John M Fitzpatrick. So eminent. So accomplished. So young.

It seemed only appropriate that within a year of his death, an international prostate cancer conference be held in his honour, in his home town of Dublin, within his beloved Aviva Stadium (formerly Lansdowne Road). Prof Fitzpatrick had published over 400 papers, performed over 90 visiting professorships, oversaw the training of over 50 Fellows, edited the BJU International for a decade, raised millions in research and charitable funding and was the recipient of a number of prestigious society medals. The conference faculty echoed this, many of whom literally travelled across the world to speak at this two-day event. Urology household names held in prestige. Like John Fitzpatrick.

The conference was divided into six sections. As with most modern scientific conferences, each of these sessions was also captured on social media using the Twitter handle @JFIPCC and the hashtag #JFIPCC, both moderated by Mr Rustom Manecksha, Tallaght Hospital, Dublin.

Session one

The first session following the opening address by the RCSI President Prof Declan Magee was titled ‘Screening and Guidelines’. It began with Prof Declan Murphy (Melbourne) describing the conflicting evidence regarding prostate cancer screening. The worrying trends in the incidence of prostate cancer, driven by negative messaging, and the inevitable increase in those presenting with more advanced disease. There was also a call to restore the balance in favour of early detection, the importance of positive patient-oriented messages, and the value of testing at an individual level. Biomarker research is accelerating; however, one must embrace a risk-adapted, multi-variable approach to the early detection of prostate cancer (Melbourne Statement).

The session moved on to the discussion of hereditary prostate cancer by Dr David Gallagher (Dublin) and the role of BRCA1/2. Prostate cancer is a heritable malignancy, with BRCA2 being both prognostic and predictive. There are other rare, highly penetrant genes which exist, eg, FOXP3, and common genomic variants account for 30 per cent of heritability, however much remains to be learned.

Prof Jack Schalken (Nijmegen) discussed the role of urinary biomarkers in the role of diagnosis and prediction of treatment response in prostate cancer, and suggested a new paradigm of diagnosis to be an SNP panel, risk stratification using biomarker panels (PHI, 4K), multi-parametric MRI and histopathology, including a molecular classifier. Prof Clare Allen (London) brought the session to a close, describing modern guidelines for standardised reporting in MRI (PI-RADS), which has been successfully developed from the system used in breast imaging.

Session two

Session two, entitled ‘Remembering John Fitzpatrick’, consisted of a number of talks recalling both the Professor’s work and his hobbies. A moving introduction by Prof Roger Kirby (London) epitomised the man through photography, statistics, humour and anecdotes in a way that only someone who knew him on a truly personal level could deliver.

The session moved forward (or backwards) into military history, one of Prof Fitzpatrick’s great interests outside urology. A talk delivered on critical moments in European history by Prof Anthony Mundy (London) — also a classics scholar — challenged the audience on some of the more important events to shape Europe, from the Greco-Roman invasions, the Mongols and Napoleon.

However, the argument was made that perhaps the crucifixion of Jesus Christ remained its most important event. Prof Culley Carson (North Caroline) and Mr Joseph Duignan (Dublin) described the role of Irish doctors in the American Civil War and the World War I respectively, while Mr John Reynard (Oxford) described medical conditions and the role of surgeons in WWI, drawing on some personal experiences from his own family.

Sessions three and four

Sessions three and four were entitled ‘Early Prostate Cancer’ and began with a sobering talk from Prof Anthony Mundy (London) on the reconstructive challenge experienced from posterior urethral injuries arising from prostate cancer treatment. He concluded that when counselling patients about the primary treatment of prostate cancer, they should be advised that although the same type of complication may occur after surgical or non-surgical treatment, the scope and scale of that complication, the ease with which it is treated and the degree of restoration of normality after treatment are altogether in favour of surgery in those for whom it is appropriate and who are fit for surgery.

Dr Stefan Machtens (Bergisch-Gladbach) highlighted some of the issues associated with focal treatment in early prostate cancer, suggesting that current diagnostic modalities are non-optimised with non-standardised follow-up, and therefore the subsequent potential for under-treatment.

Prof Louis Potter (New York) focused on a number of issues relating to organ preservation in prostate cancer and concluded that the prostate is worth preserving, treatment options need to be personalised, and the addition of LDR brachytherapy improves outcomes for all-risk CaP patients.

The session moved on to Prof Joseph Smith Jr (Tennessee) discussing the changing role of surgery in prostate cancer. After performing 10,000 radical prostatectomies, he concluded that radical prostatectomy will maintain a cardinal role in the management of prostate cancer, however, the frequency with which the operation is performed will decrease and the indications for surgery will change. Surgery will be part of a multidisciplinary approach for high-risk disease and a robotic approach will continue to dominate.

Prof Bob Bristow (Toronto) described the key players of genomics and hypoxia in prostate cancer and suggested that international collaboration should be embraced to define this heterogenic tumour signature, and to validate prognosis and predictive factors in RT/RadP with genomics.

Gene mutations and allelic changes across localised and metastatic prostate cancer could then be catalogued to understand oligomet signatures.

Prof Catharine West discussed the role of radiogenomics and predicting prostate cancer toxicity risk, and tailoring individualised treatment using SNP analysis.

The session was closed with the John Fitzpatrick BJU International Memorial Lecture, delivered by Prof Christopher Woodhouse (6th Baron Terrington; London), who eloquently described the many improvements in urology of the last century, and the role played by Prof Fitzpatrick in the creation of a better future for those he left behind.

Prof Woodhouse challenged the notion of urological nostalgia and began with the quote: “Does he not realise that, if the world were always growing worse and if fathers were generally better than their sons, we would long since have become so rotten that no further deterioration would be possible?” (Baldassare Castiglione; 1478-1529).

Prof Fitzpatrick’s life was one of achievement and knowledge bestowed. The closing statement was one from Sir James Barrie (1860-1937): “It would be a poor thing to say, in the familiar phrase, that never shall we look upon his like again; let us rather add to our confidence in the youth of our land by hoping that there will be many such as he.”

Session five

Session five continued to feature world-renowned names in prostate cancer research and treatment.

The session opened with Prof Howard Scher (New York) outlining the importance of standardised outcome measures in metastatic prostate cancer. He described how most outcomes are not validated by blood-based, imaging or patient self-reported protocols, and response is currently measured only in the disease context. There needs to be a more patient-centric approach, which will be augmented with the establishment of the PCWG-3 group to include clinical validation.

Prof John O’Leary (Dublin) illustrated the role of the platelet cloak in the metastatic cascade and mechanisms of immune evasion, whereas Prof Colleen Nelson (Queensland) discussed targeting adaptive responses to anti-androgenic therapies. Dr Paul Kelly (Cork) outlined some of the novel approaches to targeting metastatic prostate cancer with radiation therapy, and the session closed with Prof Declan Murphy (Melbourne), who delivered a state-of-the-art lecture on the emerging role of surgery in oligometastatic disease in prostate cancer. This approach is highly dependent on the quality of imaging modalities available to each unit, and made truly possible with the development of 68Ga-PSMA PET scanning, as well as the concept of ‘Vanishing M0 Syndrome’.

The rationale of surgery includes improved local control, removal of a persistent source of future metastases and improved response to systemic treatment. This is something that would have been unheard of when Prof Fitzpatrick first embarked on his illustrious career.

Final session

The final session focused on improving outcomes, and began with Prof Mike Morris (New York) discussing optimising treatment paradigms for metastatic prostate cancer. He again emphasised the importance of patient selection by analysing biochemical/genomic features of circulating tumour cells, as well as imaging assessment of molecular features, with improved endpoints such as CTCs and patient-reported outcomes.

Prof Culley Carson (North Carolina) reviewed the literature associated with penile rehabilitation, as well as his own extensive experience, and suggested that the longer the duration of erectile dysfunction after radical prostatectomy, the greater the risk of venous leakage, which is associated with a poorer prognosis. PDE5 inhibitors may be effective in helping patients with ED prophylaxis and corpus cavernosum smooth muscle rehabilitation.

Dr Derek Power (Cork) outlined some of the measures associated with bone protection in prostate cancer, and the conference concluded with Prof Ray McDermott outlining some of the collaborative approaches and international prostate cancer trials taking place in Ireland, many of which Prof Fitzpatrick himself was involved with.

Twitter

Symplur statistics demonstrated that over 500 tweets were sent using the #JFIPCC hashtag in the 48 hours around the time of the conference. There were 523,170 impressions of the conference, with 76 active participants across three continents. This was a fitting modern tribute to one the world’s most internationally recognised urologists. “His life was gentle, and the elements so mix’d in him that Nature might stand up and say to all the world, ‘This was a man!’”: Julius Caesar (V.5) — William Shakespeare (ca.1599).

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