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A tale of four

ROGER KIRBY, DAMIAN HANBURY, JOHN ANDERSON AND SEAN G. VESEY

Four urologists relate CASE 1: ROGER KIRBY their personal experiences Roger Kirby, aged 62, an otherwise of cancer and fit, asymptomatic individual who highlight some important had measured his prostate- learning points. specific antigen (PSA) for more than a decade, noticed a gradual rise in PSA to 4.3ng/ml. 3-Tesla uring the past two years, rather ironically, magnetic resonance imaging Dall four authors of this article, each a busy (MRI; Figure 1) revealed a urologist in practice with an interest in prostate suspicious focus in the right cancer, have themselves been diagnosed and peripheral zone adjacent to but not penetrating the capsule. treated for . Rather than hush Figure 1. 3-Tesla magnetic resonance image it up, as if it were a dark secret, we decided Transrectal ultrasound (TRUS)- of the prostate showing a suspicious focus in that there would be some merit in terms of guided biopsy confirmed Gleason the right peripheral zone adjacent to but not education, debate and awareness, if we were to 3+4=7 adenocarcinoma in three penetrating the capsule make public the presentation and treatment of out of 12 cores. A bone scan was negative. A robotically assisted radical was performed, by each of our four individual cases. Professor , without complications. Pathology confirmed complete excision of a Gleason 4+3=7 1.3cc tumour with invasion of the LEARNING POINTS capsule but negative surgical margins. Recovery has been uneventful. There are more than 1000 urologists presently practising in the UK. As there is a one in nine lifetime chance of being diagnosed with prostate cancer, the fact that there are at least four working urologists currently afflicted by fact, thanks to the work of Parker3 and Klotz,4 the disease is probably not surprising. The four and the publication of the NICE guidelines5 on Go to the Trends website to view a cases summarised here illustrate several prostate cancer, the majority of patients with video discussion on this subject important aspects of the management of low-risk, Gleason pattern 3+3=6 prostate with the authors: prostate cancer, an area of medicine that is cancer are now managed by active surveillance www.trendsinurology.com/videos currently changing very rapidly.1 rather than by surgery or radiotherapy.6

The first case (RK) illustrates the value of early A second learning point from this case is detection using serial PSA testing in terms of the value of high-resolution 3-Tesla MRI Roger Kirby, MA, MD, FRCS(Urol), FEBU, diagnosing prostate cancer, while it is still scanning, with gadolinium enhancement, in Director, The Prostate Centre, ; confined within the capsule of the gland, and identifying suspect areas within the gland Damian Hanbury, MS, FRCS(Urol), therefore potentially still curable. The results that can be targeted by either transrectal or Consultant Urologist, The Lister Hospital, of the European Randomized Study of transperineal ultrasound-guided biopsy (see Stevenage, Herts; John Anderson, 2 Screening for Prostate Cancer (ERSPC) Figure 1). Comparison of the preoperative MB ChB, ChM, FRCS, Consultant Urologist, confirm that mortality from prostate cancer MRI scan with the prostate itself after Royal Hallamshire Hospital, Sheffield; can be reduced by early detection, but the robotic surgery confirms the accuracy of this Sean G. Vesey, FRCS, FEBU, Retired authors worry that the lives saved will be technology in localising the tumour. This in Consultant Urologist, Southport and counterbalanced by those low-risk cases turn aids the surgeon in achieving negative Ormskirk Hospital NHS Trust, Merseyside identified who are at risk of ‘overtreatment’. In surgical margins.

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pelvic bones, which may or may not have CASE 2: DAMIAN HANBURY represented a metastasis. Fortunately, this area could be encompassed in the external Damian Hanbury, aged 55, a busy urologist in Hertfordshire, presented in beam radiotherapy field, which was used to 2010 with worsening lower urinary tract symptoms of frequency and poor treat the primary lesion. flow. A PSA measurement came back at 29ng/ml. Biopsy confirmed Gleason 4+5=9 adenocarcinoma and an MRI suggested locally advanced Case 3 (JA) is most unusual in presenting disease. There was a single suspicious focus in the pelvic bone on both with liver metastases, in spite of a normal MRI and bone scanning. A decision was made to proceed with androgen PSA only a few months before and no ablation followed by external beam radiotherapy to include the presumed metastatic focus in the pelvis. Two years on, his PSA remains undetectable other evidence of disease elsewhere. It at 0.06ng/ml. does illustrate how the PSA level can be misleading, in spite of quite large-volume metastases, especially in very poorly differentiated tumours. Hormonal therapy produced a useful but relatively short-lived The second case (DH) illustrates the not may not represent metastatic disease. In response, and fortunately taxane-based uncommon dilemma of whether to use this case there was a biopsy-proven locally chemotherapy seems to be producing a external beam radiotherapy in addition to advanced disease involving the prostate, second remission. androgen ablation when there are equivocal which was responsible for the lower urinary skeletal or soft tissue lesions, which may or tract symptoms, and a lesion within the The final case (SV) illustrates the not uncommon presentation of locally advanced disease with lymph node metastases and the subsequent development of symptomatic CASE 3: JOHN ANDERSON bone metastases requiring local radiotherapy John Anderson, aged 58, a urologist from Sheffield and President Elect of to resolve. A combination of androgen the British Association of Urological Surgeons, was perfectly well and ablation with taxane-based chemotherapy without symptoms in early October 2011, and had a routine PSA test, and additional abiraterone7 has produced a which came back at 1.7ng/ml. On 27 January 2012 (only four months prolonged response. The new oral agent later) he felt a mass in the upper abdomen and a computed tomography enzalutamide,8 which has produced (CT) scan confirmed multiple liver metastases with no other detectable impressive results in clinical trials, and abnormality. With a normal PSA four months earlier, no urinary symptoms the encouraging clinical profile of the and no extrahepatic disease visible on the scan, the possibility of this alpha-pharmaceutical Alpharadin,9 are being related to the prostate never really crossed anyone’s mind. A the next therapeutic options. couple of weeks later, a liver biopsy confirmed a poorly differentiated adenocarcinoma. Subsequent immunohistochemistry of the liver biopsies DISCUSSION stained positive for PSA, which confirmed the diagnosis of metastatic Anxieties about overtreatment of low-risk, prostate cancer. It was only then that the serum PSA was measured, which had risen from normal 1.7 to 92.7ng/ml in four months. low-volume Gleason 3+3=6 prostate cancers Androgen deprivation therapy resulted in a PSA nadir of 0.2ng/ml have fostered the myth that prostate cancer after four months of treatment, but the PSA then started to climb. In is somehow a toothless tiger. Consideration November, he developed sudden-onset severe right-sided abdominal pain of the four clinical situations above, drawn requiring opiates to control symptoms. A further CT still showed no from the ranks of actively practising evidence of disease outside of the liver, although the liver metastases had urologists, clearly illustrates that this is not increased considerably in size and were considered the likely explanation always the case. for the pain. The PSA at this time was 483ng/ml. In view of the symptoms and progressive disease, docetaxel-based chemotherapy was commenced. Progress with treatment is being made with After two cycles the pain has improved significantly, the PSA has fallen kinder, minimally invasive, robotically somewhat and he is back playing golf. The side-effects from the assisted surgery and better targeted, more chemotherapy are not too bad, other than he has lost his taste for white powerful radiotherapy. Androgen ablation wine! Abiraterone/enzalutamide are further treatment options if there is therapy still provides the mainstay of therapy further disease progression. for metastatic disease, but abiraterone, enzalutamide, Alpharadin and chemotherapy

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triggers for intervention. Curr Opin Urol CASE 4: SEAN VESEY 2012;22:210–5. 4. Klotz L. Active surveillance for favorable-risk Sean Vesey, aged 58, a laparoscopic radical prostatectomist from prostate cancer: background, patient Merseyside, presented in early 2010 with left iliac fossa discomfort, which selection, triggers for intervention, and prompted investigations, including a PSA. This came back at 78ng/ml. outcomes. Curr Urol Rep 2012;13:153–9. His PSA had been just 1.4ng/ml some 18 months earlier. TRUS biopsy 5. NICE. Prostate cancer: diagnosis and confirmed T3b Gleason 4+3=7 adenocarcinoma in all cores and an MRI treatment. Clinical guideline 58. February revealed pelvic and para-aortic lymphadenopathy. Although the original 2008. http://guidance.nice.org.uk/CG58 bone scan was clear, a subsequent bone scan at one year confirmed the 6. Godtman RA, Holmberg E, Khatami A, et al. presence of bone metastases in the cervical and lumbar spine. Initial hormonal therapy reduced the PSA to a nadir value of 8.9ng/ml. Three Outcome following active surveillance of cycles of chemotherapy followed by abiraterone further reduced the PSA men with screen-detected prostate cancer. to 0.27ng/ml. Although he is currently well, local radiotherapy has been Results from the Göteborg randomised administered to a new pelvic metastasis. The new agent enzalutamide is population-based prostate cancer screening being considered and radium-223 chloride is now being administered. trial. Eur Urol 2013;63:101–7. 7. Ryan CJ, Smith MR, de Bono JS, et al; the COU-AA-302 Investigators. Abiraterone in metastatic prostate cancer without with taxotere or cabazitaxel are all now There is at last a realistic prospect for more previous chemotherapy. N Engl J Med useful, evidence-based, second-line options targeted screening of those most susceptible 2013;368:138. when hormone relapse occurs.10 to the disease.14 More than 30 prostate 8. Berruti A, Generali D, Tampellini M. cancer susceptibility genes have been Enzalutamide in prostate cancer after One key question is whether or not we identified and it seems possible that men chemotherapy. N Engl J Med 2012;367: should all carefully monitor our own, and our unlikely to develop prostate cancer could be 2448–9. patients’, PSA levels over time, and respond excluded from screening protocols and 9. Croke J, Leung E, Segal R, Malone S. Clinical to a rise by organising a 3-Tesla MRI and a instead attention focused on those most benefits of alpharadin in castrate- targeted biopsy of the prostate to achieve likely to develop the disease. chemotherapy-resistant prostate cancer: case early detection. In one of the four cases (JA), report and literature review. BMJ Case Rep the PSA was negative only a few months Much remains to be done to improve 2012; doi: 10.1136/bcr-2012-00654. before presentation; in another (SV), the PSA awareness about the risks of prostate cancer, 10. Kirby R, Fitzpatrick JM. Improved survival rose from 1.4 to 78ng/ml over an 18-month not only among urologists, but also family prospects for patients with castration- time frame. Clearly, annual PSA testing would practitioners and the general public. resistant prostate cancer. BJU Int 2011; not have been helpful in either of these Although screening is still controversial, 107:697–700. situations. New, better ways are needed to better treatments for hormone-relapsed 11. Andriole GL, Crawford D, Grubb RL, et al. identify poorly differentiated, aggressive disease are now becoming available. We Mortality results from a randomized prostate cancers as they often do not sincerely hope that the openness about our prostate-cancer screening trial. N Engl J Med manufacture and secrete PSA in their early, own diagnoses and management will help to 2009;360:1310–19. potentially curative stages. dispel the taboo that still haunts this most 12. Bill-Axelson A, Holmberg L, Filén F, et al. common of cancers of men. for the Scandinavian Prostate Cancer Group The debate about screening for prostate Study Number 4. Radical prostatectomy cancer seems likely to run and run, especially REFERENCES versus watchful waiting in localized prostate since the ERSPC2 reported a positive result, 1. Kirby RS, Challacombe B, Dasgupta P, cancer: the Scandinavian Prostate Cancer while the US-based Prostate, Lung, Colorectal Fitzpatrick JM. Prostate cancer treatment: Group-4 Randomized Trial. J Natl Cancer Inst and Ovarian (PLCO) cancer screening trial11 the times they are a’ changin’. BJU Int 2008;100:1144–54. produced a negative one. To compound the 2012;110:1408–11. 13. Wilt TJ, Brawer MK, Jones KM, et al. Radical problem, while a Scandinavian study of radical 2. Schröder FH, Hugosson J, Roobol MJ, prostatectomy versus observation for prostatectomy versus watchful waiting et al. Prostate-cancer mortality at localized prostate cancer. N Engl J Med revealed a survival advantage for patients 11 years of follow-up. N Engl J Med 2012;367:203–13. treated surgically,12 the US-based Prostate 2012;366:981–90. 14. Kirby RS, Eeles RA, Kote-Jarai Z, et al. Cancer Intervention versus Observation Trial 3. Lees K, Durve M, Parker C. Active surveillance Screening for prostate cancer: the way ahead. (PIVOT) showed no benefit.13 in prostate cancer: patient selection and BJU Int 2010;105:295–7.

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