BJUI awards three ‘Best Paper’ prizes.
All three focus on prostate cancer.
THE BOB KRANE PRIZE
E. David Crawford, MD
Distinguished Professor of Surgery, Urology and Radiation Oncology
Head, Section of Urologic Oncology, University of Colorado Anschutz Medical Campus
Denver, Colorado, USA
Crawford ED, Moul JW, Rove KO et al.
Prostate-specific antigen 1.5–4.0 ng/mL: a diagnostic challenge and danger zone.
BJU Int 2011; 108: 1743–9
HIGHLY COMMENDED: Jérémie Haffner, MD
Department of Urology, Université Lille Nord de France, Lille, France
Haffner J, Lemaitre L, Puech P et al. Role of magnetic resonance imaging before initial biopsy: comparison of magnetic resonance imaging-targeted and systematic biopsy for significant prostate cancer detection. BJU Int 2011; 108 (8 Pt 2): E171–8
One is a resident from France ready for his robotics fellowship in Montreal. Another is a genetics researcher in Calgary who keeps his hand in with clinical urology. And, finally, the third is a distinguished professor in Denver who Men's Health magazine named as one of the top 20 urologists in the country. All three are BJUI's 2012 winners for the best papers published in a given year. While each hails from different parts of the globe, they all share a passion for excellence in urology and patient care. Just like last year, all three winning papers focus on some aspect of prostate cancer.
‘It never ceases to amaze me how much talent is behind the papers we receive at the journal each year,’ says John Fitzpatrick, editor-in-chief of BJUI. ‘This year's recipients represent some of the best and the brightest in our specialty.’ Both winners of the Bob Krane and Don Coffey Prizes were honoured at an exclusive cocktail reception during the American Urological Association (AUA) annual meeting. The winner of the John Blandy Prize delivered an honorary lecture at the yearly meeting of the British Association of Urological Surgeons (BAUS).
KRANE WINNER SEES A DANGEROUS PSA THRESHOLD
Each year, the Bob Krane Prize is awarded for the best clinical paper. This year's winner, E. David Crawford, MD, knew the late Bob Krane quite well and was ‘very surprised and yet excited’ when he received the news that he had won. ‘Bob was a great guy,’ remembers Dr Crawford. ‘To have the honour of my name being associated with him is indeed something that touches me deeply.’
His paper points to a PSA threshold of 1.5 ng/mL as a potential danger zone when it comes to predicting an increased risk for prostate cancer over a 4-year period. The study found that prostate cancer rates were 15-fold higher in patients with a PSA at or above this threshold compared with patients with PSA levels below it. The risk was even higher for African-American patients, with a 19-fold increase in prostate cancer.
‘The idea for the paper came out of a National Institute of Health trial that we had for BPH called the Medical Therapy of Prostatic Symptoms study,’ says Dr Crawford. ‘A PSA of 1.5 was a surrogate for prostate size and the progression of BPH.’ He is quick to point out that some patients regard a PSA of 1.7 as nothing to worry about, thinking they are in great shape. ‘Knowing what I know about prostate cancer, I'd want something done if I had a PSA of 1.5 or 1.7,’ he says. According to Dr Crawford, a first PSA threshold of 1.5 and above or somewhere between 1.5 and 4.0 is what he calls the ‘early-warning PSA zone’ (EWP zone). This should get patients and clinicians to start thinking about doing something now and in the future regarding prostate cancer and BPH.
Dr Crawford believes that his study will have long-term significance and implications. ‘People a year or two from now will realize this is a landmark paper,’ he says. When asked about what makes a good paper, his response was rather philosophical yet direct. ‘In clinical research, you have to do something that matters. It doesn't have to be earth shattering – just a step forward!’
BLANDY GOES TO PROLIFIC YOUNG UROLOGIST
The John Blandy Prize is awarded to the best paper published by a resident. As with last year's winner, Guillaume Ploussard was given the prize for five papers that were published during 2011 alone (two are listed in the sidebar). ‘The aim of these papers was to illustrate the important developments in prostate cancer diagnosis and therapeutic strategy during the last decade,’ he points out. Many of the papers used analyses from the prospective database at his institution. ‘The findings presented in the papers were from a single centre experience, but I hope that they might reflect the real evolution of prostate cancer management in France,’ Dr Ploussard explains.
Since publication of his papers in BJUI, he has been busy updating many of the results. These include his work on the stage migration of prostate cancer, the prognostic value of PCA3, and outcomes following radical prostatectomy for high risk prostate cancer. Dr Ploussard is especially keen on having his studies linked to routine clinical practice. ‘I hope that some conclusions might help physicians in daily practice, especially the interest in adjuvant therapy after radical prostatectomy,’ he says. ‘My papers reflect two great evolutions in prostate cancer over the last decade: the impact of prostate cancer screening and the learning curve in robot-assisted radical prostatectomy.’
THE DON COFFEY PRIZE
Tarek Bismar, MD
Department of Pathology and Laboratory Medicine
University of Calgary Faculty of Medicine
Calgary, Alberta, Canada
Bismar TA, Yoshimoto M, Vollmer RT et al.
PTEN genomic deletion is an early event associated with ERG gene rearrangements in prostate cancer.
BJU Int 2011; 107: 477–85
HIGHLY COMMENDED: Satish K Tickoo, MD
Department of Pathology, Genitourinary Oncology Service
Memorial Sloan-Kettering Cancer Center, New York, USA
Tickoo SK, Milowsky MI, Dhar N et al.
Hypoxia-inducible factor and mammalian target of rapamycin pathway markers in urothelial carcinoma of the bladder: possible therapeutic implications.
BJU Int 2011; 107: 844–9
Now just after receiving his PhD in molecular biology, Dr Ploussard is off to McGill University in Montreal where he will start a fellowship in robotics. Some of his prize money will go to spending some much deserved weekends with family in the Laurentides. He is very inspired by Dr John Blandy, whom he calls ‘a high calibre urologist who promoted our specialty as a separate entity’. For residents, he would like to see a real programme of practice teaching in operating rooms so that a resident's learning curve on each urological procedure could be assessed prospectively. In addition, he would like to see an increase in clinical research opportunities after residency. What makes a good research paper? Dr Ploussard's answer was straight to the point: ‘one database, one simple question, one response’.
COFFEY WINNER GETS INSPIRATION FROM PATIENTS
Those who are awarded the Coffey Prize have written the best research paper for BJUI. This year's winner, Tarek A Bismar, MD, has already reaped additional rewards for winning the award. He's been given more time to do research, specifically 60%, with the remaining 40% of his time devoted to clinical practice. For Dr Bismar, that's perfectly fine with him. ‘I don't want to completely leave my clinical practice,’ he admits. ‘The inspiration for my research questions actually comes from my patients.’
Dr Bismar's winning paper sheds light on the importance, both singularly and in combination, of ERG gene rearrangements and PTEN genomic deletions in the development and progression of prostate cancer. ‘We found the incidences of ERG rearrangements and PTEN deletions to be significantly higher in prostate cancer compared with high grade prostatic intra-epithelial neoplasia (HGPIN) and benign prostate tissue,’ he says of the findings.
Since publication of his paper, Dr Bismar has received a lot of requests for reprints. In addition, it has already been cited in several articles. His next step is to look at HGPIN lesions with both ERG gene rearrangements and PTEN genomic deletions to see if these patients have a higher chance of developing cancer compared with patients with just one situation. ‘If you want to slow disease progression, you need something to work against these two activities,’ Dr Bismar explains. ‘By showing that patients with HGPIN have both ERG gene rearrangements and PTEN genomic deletions, we can then offer them earlier treatment.’
While Dr Bismar didn't know Dr Coffey before receiving the award, he certainly knows a lot about him now. Upon hearing that Dr Bismar had won the Don Coffey Prize, a fellow urologist gave him a biography on the man behind the award. ‘This is a very prestigious award to have,’ he says excitedly.
‘I am really happy!’
THE JOHN BLANDY PRIZE
Guillaume Ploussard, MD, PhD
Department of Urology
Public Assistance Hospitals of Paris
Heni Mondor University Hospital, France
Ploussard G, Agamy MA, Alenda O et al.
Impact of positive surgical margins on prostate-specific antigen failure after radical prostatectomy in adjuvant treatment-naïve patients. BJU Int 2011; 107: 1748–54
Ploussard G, de la Taille A, Xylinas E et al.
Prospective evaluation of combined oncological and functional outcomes after laparoscopic radical prostatectomy: trifecta rate of achieving continence, potency and cancer control at 2 years. BJU Int 2011; 107: 274–9
THE BEYOND STUDY COMPARING MIRABEGRON TO SOLIFENACIN IN PREVIOUSLY TREATED PATIENTS WITH OVERACTIVE BLADDER
PROTOCOL ID NCT 01638000
SUMMARY This double-blind, randomized, phase 3 study will evaluate the efficacy and safety of mirabegron compared with solifenacin in patients with overactive bladder. All participants must have been treated previously with antimuscarinics and be dissatisfied with their treatment owing to lack of efficacy. The primary outcome measure will be the change from baseline in the mean number of micturitions per 24 h up to 12 weeks.
ELIGIBILITY Subjects can be men and women aged18 and older. Their symptoms of overactive bladder (urinary frequency and urgency with or without urgency incontinence) must be 3 months in duration or longer prior to study entry. In addition, they must be currently taking or have been on at least one antimuscarinic agent. It must have been taken for at least 4 weeks and taken within 6 months prior to the screening visit. During the study, participants will complete a micturition diary and answer questionnaires. An estimated 1692 men and women will be enrolled in this study.
LOCATIONS & CONTACT There are 220 study locations at centres throughout Europe and the Middle East, including the UK. Contact Astellas Pharma Inc., Medical Affairs Europe, at +31 (0) 71 545 5878, e-mail: email@example.com.
PEOPLE & PLACES
Pasquale Casale, MD has been appointed as the new chief of paediatric urology at New York-Presbyterian/Morgan Stanley Children's Hospital in New York City. Dr Casale arrives from the Children's Hospital of Philadelphia, where he was director of minimally invasive surgery and robotic surgery. He also served as co-director of its surgical simulation and training laboratory. In New York, Dr Casale will also be a professor of urology at Columbia University College of Physicians and Surgeons.
Joining Dr Casale is Sarah Lambert, MD who also comes from the Children's Hospital of Philadelphia. Her new appointment at New York-Presbyterian will be attending physician in the paediatric urology department and assistant professor of urology at Columbia, where she received her medical degree and did her residency in urology.
Michael Cookson, MD has been invited to join the American Association of Genitourinary Surgeons (AAGUS) as its latest member. Dr Cookson is the Patricia and Rodes Hart Chair in Urologic Surgery at Vanderbilt University in Nashville, TN. He joins three others from Vanderbilt as AAGUS members, the largest group from any single institution in the country. Dr Cookson is also co-director of urological oncology and directs the fellowship programme in urological oncology at the Vanderbilt-Ingram Cancer Center. AAGUS was founded in 1886 to promote the study of diseases of the genitourinary system. With membership limited to 75 distinguished urological surgeons, the Association is the most prestigious organization for such specialists. Visit them at http://www.aagus.org. Vanderbilt has also announced the appointment of David Penson, MD MPH, to the National Advisory Council for Healthcare Research and Quality. The Council is part of the Agency for Healthcare Research and Quality (AHRQ) of the US Department of Health and Human Services. At Vanderbilt, Dr Penson serves as professor of urological surgery and director of the Center for Surgical Quality and Outcomes. The Council consists of 21 members who are researchers, consumers, providers and policy-makers. Their goal is to guide AHRQ on where to focus its programmes in the areas of quality, clinical outcomes and cost-effectiveness research. Visit AHRQ at http://www.ahrq.gov.
Gregory Bianchi, MD, MS has joined the Division of Urologic Surgery at the University of North Carolina in Chapel Hill, where he recently completed a residency in anatomic pathology. He is assistant professor of urology and assistant professor of pathology. During his residency in urology at the University of Iowa, Iowa City, Dr Bianchi also obtained a masters degree in science in prevention medicine and environmental health with an emphasis on urological cancer epidemiology. He received fellowship training in endourology, laparoscopy and robotic surgery at the University of Cincinnati College of Medicine.
DRUG AND TECHNOLOGY NEWS
NEW GENETIC TEST DEVELOPED FOR PROSTATE CANCER
Researchers from the University of California San Diego School of Medicine have developed a genetic scoring test to help predict prostate cancer risk. The test looks for the presence of germline single nucleotide polymorphisms (SNPs). According to Karim Kader, MD, PhD, a co-investigator, ‘the genetic test outperformed the PSA test in assessing cancer risk’.
A total of 1654 men from the placebo arm of the randomized Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial participated in the study. All had an initial negative prostate biopsy and were then rebiopsied at 2 and 4 years per the REDUCE study protocol. The researchers looked at the predictive performance of baseline clinical parameters as well as each man's genetic score based on 33 established prostate cancer risk associated SNPs.
The genetic score was found to be a significant predictor of a positive biopsy. This continued to be true after the researchers adjusted for clinical variables and the man's family history. Adding the genetic score to the best clinical model was particularly beneficial for men with intermediate clinical risk for prostate cancer following an initial negative prostate biopsy.
More details about this study can be found in the 16 May online edition of European Urology.
QUALITY STANDARDS ISSUED FOR ABSORBENT PRODUCTS
US national quality performance standards have been released for disposable adult absorbent products for incontinence in the frail, elderly and/or disabled populations. The recommendations were issued by a council headed by the National Association for Continence (NAFC). They are designed to guide state Medicaid programmes as well as purchases by consumers, hospitals, nursing homes, hospice programmes and other providers.
According to the NAFC, the recommendations cover eight specific characteristics, including how well the product withstands multiple incontinent episodes (rewet), the speed at which urine is drawn away from the skin (rate of acquisition) and the product's capacity to hold fluid without leaking (retention capacity). The recommendations also include advice on sizing options, safety issues, closure systems, breathable zones and faecal containment.
The council met monthly for the past year and a half to develop the new recommendations. They are available online at NAFC's website (http://www.nafc.org) for public vetting and comments until early September. Following feedback review on the draft, the final recommendations will be released before the end of the year.
MEDITERRANEAN WEED COMPOUND KILLS PROSTATE TUMOURS
Arab nomads called it the ‘death carrot’. If camels ate the plant, they would die. Ancient Greeks knew it was toxic to animals. Now, Thapsia garganica, a weed that grows naturally in the Mediterranean region, may have a life-saving role. Researchers from the Johns Hopkins Kimmel Cancer Center have discovered that a compound from the weed, called G202, reduces the size of human prostate tumours grown in mice.
G202 blocks the function of the sarcoplasmic/endoplasmic reticulum calcium adenosine triphosphatase (SERCA) pump, an intracellular protein critical for all cells to keep calcium levels at the correct balance. Since the SERCA pump is required by every cell to stay alive, it is unlikely that tumour cells will become resistant to G202.
A three-day course of G202 produced significant tumour regression against a panel of human cancer xenografts in mice. After 30 days, the size of these human prostate tumours grown in mice decreased an average of 50%. G202 was found to outperform docetaxel. Whereas docetaxel reduced only one of eight tumours by more than 50%, G202 reduced seven of nine tumours in the same 30-day period. The compound also has a similar effect on breast, kidney and bladder cancers.
A chemically modified G202 is now being tested in a phase 1 clinical trial of 29 patients with advanced cancer. There are plans for a phase 2 trial to test G202 in patients with prostate and liver cancer. In prostate cancer, the injected drug travels to the cancer cells and hits prostate-specific membrane antigen (PSMA). PSMA acts as the puller of a hand grenade pin by forcing G202 to release cell-killing agents into the tumour and surrounding blood vessels.
The study was published in the 27 June issue of Science Translational Medicine 2012; 4 (140): 140ra86.
IMPORTANT PAPERS YOU MAY HAVE MISSED…
•Activated RAS and FGFR3 do not appear to be drivers in bladder cancer. Ouerhani S and Elgaaied ABA. Cancer Biomark 2012; 10: 259–66
•ASCO weighs in on PSA testing for prostate cancer screening. Basch E, Oliver TK, Vickers A et al. J Clin Oncol 2012; July 16 [Epub ahead of print]
• Combined antibiotic prophylaxis reduces infective complications after prostate biopsy. Chan ES, Lo K, Ng C et al. Chin Med J 2012; 125: 2432–5
•Radical prostatectomy does not significantly lower all-cause or prostate-cancer mortality compared to observation. Wilt TJ, Brawer MK, Jones KM et al. N Engl J Med 2012; 367: 203–13
• Marker half life predicts recurrence of testicular cancer. Keskin S, Ekenel M, Ba_aran M and Bavbek S. Am J Clin Oncol 2012; 35: 369–72
In this issue…
Lower Urinary Tract
NOCTURIA MAY BE MARKER FOR INCREASED RISK OF HEART DISEASE AND DEATH P848
Awakening at night to void is a common complaint of men, particularly as they age. In their cohort of 2447 men, Lightner et al investigate the relationship between nocturia and the later development of diabetes, hypertension, coronary heart disease (CHD) and death. They found that nocturia appears to be a marker for increased risk of CHD in younger men. For older men age 60 years and over, however, nocturia was associated with an increased risk of death.
The ages of the men in this retrospective cohort of randomly selected men ranged from 40 to 79 years. All complained of waking up two or more times a night to urinate. Since 1990, the cohort was followed every 2 years with symptom questionnaires as well as medical record reviews. The median follow-up was 17.1 years.
No significant association was found between nocturia and the later development of diabetes or hypertension. However, the men younger than 60 years who experienced moderate nocturia were more likely to develop CHD in their later years compared with men without the complaint. The researchers found, though, that after adjusting for age, body mass index and urological medications, this relationship was no longer significant. Men 60 years of age and older with moderate nocturia were more likely to die compared with their peers without nocturia. In these cases, this association continued even after adjusting for age, body mass index, urological medications and CHD.
Laparoscopic and Robotic Urology
ANTERIOR SUSPENSION WITH POSTERIOR RECONSTRUCTION IMPROVES EARLY CONTINENCE AFTER ROBOTIC PROSTATECTOMY P875
Regardless of the surgical technique used, urinary incontinence remains an unwanted side effect after radical prostatectomy. One-year continence rates are excellent after robot-assisted laparoscopic prostatectomy (RALP); however, the earlier return of continence remains challenging. Both posterior reconstruction of the rhabdomyosphincter and restitution of anterior attachments of puboprostatic ligaments using an anterior suspension have been used separately to improve postoperative continence. Hurtes et al offer their experience with using a combination of these two techniques in patients undergoing RALP. They find that anterior suspension associated with posterior reconstruction improved early continence at 1 and 3 months after surgery.
The study involved randomizing 72 patients from three centres into one of two groups. The first group of 33 men underwent standard RALP, while the second group of 39 had anterior suspension and posterior reconstruction as part of their RALP. Continence was measured at baseline and then at 15 days after surgery using a validated questionnaire. Measurements continued at 1, 3 and 6 months.
Continence rates (defined by the UCLA Prostate Cancer Index) in the standard RALP group were 3.6% after 15 days, 7.1% after 1 month, 15.4% after 3 months and 57.9% after 6 months. Such rates in the suspension/reconstruction group were 5.9%, 26.5%, 45.2% and 65.4%, respectively. Significant improvements were most noted at 1 and 3 months. There were no significant differences between the groups in terms of complication rates. In addition, no significant urinary stricture was found in either group.
PATHOLOGICAL FEATURES PREDICT PROGNOSIS OF UNCLASSIFIED RENAL CELL CARCINOMA P786
Introduced in 1997, unclassified renal cell carcinoma (RCC) is a diagnostic category subtype for tumours that cannot be classified into any of the four existing categories. Such tumours tend to be heterogeneous and high grade. Lopez-Beltran et al present their series of 56 cases of unclassified RCC, focusing on their clinicopathological features and outcomes. Their findings show that a number of these factors can predict prognosis. Of note was tumour size, which was found to be the most significant independent predictor of disease-free survival in these patients.
Cases of unclassified RCC were culled from centres in the USA and Europe. Independent uropathologists reviewed pathology reports, specimen photographs and histological material. Several clinicopathological features were examined, including nuclear grade, pT status, tumour size, lymph node involvement, distant metastases, coagulative tumour necrosis, mucin and sarcomatoid differentiation.
Of the 56 cases, 34 were unrecognizable cell type with a mean survival of 47 months. Another 20 cases were composites of recognized types. Their mean survival was 36 months. The lowest survival of 16 months was for the remaining two cases of pure sarcomatoid morphology without recognizable epithelial elements. In these instances, mean survival was just 16 months. Factors found to be independent predictors of disease-free survival were nuclear grade, tumour coagulative necrosis, tumour size, microvascular invasion and tumour histotype. All of these, as well as tumour recurrence after surgery, were independent predictors of cancer-specific survival, with tumour recurrence being the strongest.