MEETING REvIEw
Updates in the Care and Management of Prostate Cancer Highlights From the 2013 Prostate Cancer World Congress, August 6-10, 2013, Melbourne, Australia [ Rev Urol. 2013;15(4):185-187 doi: 10.3909/riu0599]
®
© 2014 MedReviews , LLC
KEY WORDS Active surveillance • Health disparities • Prostate cancer • Consensus statement • Pre-biopsy rectal swab
T
he Prostate Cancer World Congress (PCWC) was held in Melbourne, Australia, August 6-10, 2013, incorporating the 14th Australasian Prostate Cancer Congress. This meeting included more than 1000 delegates from around the world. There were three parallel streams for clinical urology, translational science, nursing/allied health, and general practice, with a total of 174 abstract presentations. Reviewed by Marnique Basto, Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; Áine Goggins, Department of Medicine, Queen’s University, Belfast, UK; Stacy Loeb, MD, Department of Urology and Population Health, New York University and the Manhattan Veterans Affairs Hospital, New York, NY.
In the Clinical Urology program, prostate biopsy infections were an overarching theme following suit from the 2013 American Urological Association meeting held in San Diego, California. Indeed, numerous studies have raised concern about rising infectious complications after transrectal ultrasound (TRUS)–guided biopsy in the global setting of increasing antimicrobial resistance, leading to ongoing investigation into ways to reduce prostate biopsy risks.1 One strategy that has been recently investigated is the use of pre-biopsy rectal swab cultures. New data from Norris and colleagues found a 3.73% prevalence of extended spectrum B-lactamase (ESBL) carriage on pre-biopsy rectal swab in 53 patients from an Australian tertiary institution.2 Of interest, though, was that none of the 3.73% Vol. 15 No. 4 • 2013 • Reviews in Urology • 185
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Updates in the Management of Prostate Cancer continued of patients with infectious complications were noted to have ESBL carriage. Additional investigation is ongoing to determine whether pre-biopsy questionnaires can help identify the patients at greatest risk for antimicrobial resistance. In a prospective study of 124 men from New Zealand, Losco and Studd reported a zero sepsis rate in a high-risk cohort (n 5 62 men with previous TRUS or urosepsis, who were immunocompromised, or noted recent ciprofloxacin use or overseas travel) with the addition of ertapenem to standard prophylaxis.3 This compared with a 9.6% rate in low-risk patients (P 5 .03) who received the standard regimen of ciprofloxacin and amoxicillin. Of these, half grew ciprofloxacin-resistant organisms. Another large study by Leahy and colleagues that included 1937 patients from a single private Australian institution reported a 1.2% readmission rate for infection.4 They reported increasing use of carbapenems both as treatment for sepsis (58.7%) and for prophylaxis (8%), highlighting urologists’ concern over the increasing prevalence of multidrug-resistant bacteria. Although expanded antimicrobial prophylaxis is another possible way to reduce infections, a drawback to this approach is the potential for increased resistance in the future. Other studies evaluated the emerging role of transperineal template biopsy in Australia in reducing infectious complications and potentially improving cancer detection. Huang and colleagues suggested it be offered as an option for all repeat prostate biopsies given a zero sepsis rate and a 35% detection rate in those with a previously negative TRUS biopsy.5 Of these, 79% had anterior/transition zone tumors. Complications included
a 6.3% rate of acute urinary retention and a 2.7% rate of clot retention. Grummet and colleagues similarly reported a zero sepsis rate in a multi-institutional study in Victoria of 245 patients undergoing transperineal prostate biopsy.6 The authors concluded that, in the context of increasing multiresistant rectal flora, transperineal template biopsy is the preferred approach. However, most biopsies in Australia are already performed with anesthesia in the operating theater, so the translation of these findings to other settings where prostate biopsy is typically done in the outpatient clinic requires further investigation. Active surveillance (AS) was another key focus at the PCWC. Adoption rates of AS for low-risk prostate cancer in Australia are increasing, with recently published data from Victoria (2008-2011) reporting 40.6% uptake,7 which continues to expand. In a retrospective review of 409 patients, Satasivam and associates reported that 78% of low-risk men chose AS, with rapidly decreasing numbers undergoing radical prostatectomy, from 50% in late 2010 to 0% in 2013 (P 5 .009 for trend).8 However, concerns about the accuracy of pretreatment risk classification remain an issue. A study from Hong Kong sought to identify predictive factors for indolent disease at radical prostatectomy for those who met AS criteria.9 Only maximum percentage of cancer per core (, 50%) was associated with indolent disease at prostatectomy (P , .05). Because this variable is not currently included in the commonly used Prostate Cancer Research International Active Surveillance criteria, the authors suggested that it may be an important consideration for AS patient selection moving forward.
Another study of 161 low-risk patients from Korea found that the maximum core percentage of longest tumor (P 5 .002) and the percentage of positive cores (P 5 .019) were significant predictors of pathologic stage $ T3 disease.10 These combined findings suggest that biopsy core data are useful factors to consider when counseling patients about selection of treatment versus AS. An additional topic of discussion was the potential for anxiety among men choosing AS. However, Anderson and associates reported low levels of prostate cancer–related anxiety in the vast majority of patients (87%).11 This was likely attributable to the high levels of patient education reported by 92% of men in this study. Meanwhile, younger age and underlying anxiety traits were significant predictors for anxiety on AS and these patients may benefit from targeted education or more active therapy. Finally, another subject of controversy is whether short-term treatment delay could lead to a decrement in outcomes. A large UK study found no significant difference in survival rates between those who had surgery within 0 to 3 months versus 4 to 6 months after diagnosis,12 although additional long-term follow-up studies are important to further evaluate this issue. Another key theme at PCWC was health disparities between ethnic and sociodemographic groups. Winners of the Best Poster in Clinical Urology, Obertova and colleagues found that Māori men in New Zealand were more likely to have metastatic disease at diagnosis and were significantly more likely to die from prostate cancer than non-Māori men (HR, 2.95; 95% confidence interval [CI], 2.31-3.77).13 Similarly, Smith
186 • Vol. 15 No. 4 • 2013 • Reviews in Urology
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Updates in the Management of Prostate Cancer and colleagues reported that Aboriginal men in Australia had a 53% higher probability of death from prostate cancer at 5 years (17.5%; 95% CI, 12.4-23.3) compared with non-Aboriginal men (11.4%; 95% CI, 11.0-11.8).14 Finally, another New Zealand study observed lower prostate-specific antigen (PSA) screening rates in rural areas compared with main urban areas (17.6% vs 25.6%; P 5 .0001).15 Furthermore, PSA was more likely to be elevated at diagnosis in rural men (P 5 .0014). These studies demonstrate the need for additional measures to help bridge these health disparities. Undoubtedly, the major highlight of the meeting was the release of the Melbourne PSA Consensus Statement led by Dr. Declan Murphy, honorary clinical associate professor at the University of Melbourne and consultant urological surgeon at the Peter MacCallum Cancer Centre, along with an international faculty of world leaders in prostate cancer, including Tony Costello, Patrick Walsh, Thomas Ahlering, William Catalona, Oliver Sartor, Tom Pickles, Noel Clarke, Matthew Cooperberg, David Gillatt, Martin Gleave, Stacy Loeb, and Monique Roobol.16 In summary, the following recommendations were made: (1) for men aged 50 to 69 years, Level 1 evidence demonstrates that PSA testing reduces prostate cancer–specific
mortality and the incidence of metastatic prostate cancer; (2) prostate cancer diagnosis must be uncoupled from prostate cancer intervention; (3) PSA testing should not be considered on its own, but rather as part of a multivariable approach to early prostate cancer detection; (4) baseline PSA testing for men in their 40s is useful for predicting the future risk of prostate cancer; (5) older men in good health with over a 10-year life expectancy should not be denied PSA testing on the basis of their age. Overall, PSA remains a critical part of prostate cancer risk assessment that should be offered as part of a shared decision-making process. There is now definitive evidence demonstrating a diseasespecific mortality benefit with screening and it remains the only way to identify aggressive tumors in time for curative intervention. Conversely, many men with low-risk disease can be safely managed conservatively, highlighting the importance of dissociating diagnosis from treatment. The recommendations regarding the age to discontinue screening are also important considering that the average life expectancy of an Australian man at age 70 is 15 years. Given the many different prostate cancer guidelines currently in circulation, it is hoped that the Melbourne Consensus Statement will help bring clarity to these controversial issues.
References 1.
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3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
Loeb S, Vellekoop A, Ahmed HU, et al. Systematic review of complications of prostate biopsy. Eur Urol. 2013;64:876-892. Norris B, DeSousa T, Anderson P, Huang J. TRUS biopsy in the superbug era. Prevalence and predictors of ESBL carriage in an Australian tertiary hospital. BJU Int. 2013;112(suppl 1):25. Abstract 25762. Losco F, Studd R. Post-TRUS sepsis: targeted use of prophylactic ertapenem for high-risk patients. BJU Int. 2013;112(suppl 1):7. Abstract 4462. Leahy O, O’Reilly M, Phillips D, Grummet J. TRUS biopsy sepsis and use of carbapenem antibiotics at a single high volume local institution. BJU Int. 2013;112(suppl 1):26. Abstract 25802. Huang S, Reeves F, Preece J Grummet J. Transperineal template biopsy of the prostate: a review of the impact at Alfred Health. BJU Int. 2013;112(suppl 1):26. Abstract 25778. Grummet J, Weerakoon M, Huang S, et al. Sepsis and superbugs: should transperineal biopsy be offered to all prospective prostate biopsy patients? BJU Int. 2013;112(suppl 1):26. Abstract 25798. Evans SM, Millar JL, Wood JM, et al. Patterns of care for men diagnosed with prostate cancer in Victoria from 2008 to 2011. Med J Aust. 2013;198:540-545. Satasivam P, Vijayan S, Frydenberg M, Appu S. Contemporary management of prostate cancer at an Australian tertiary referral centre. BJU Int. 2013;112(suppl 1):17. Abstract 25094 Chan M, Yu C, Gheng C, Chu P. Be prepared for active surveillance. What should the patient and I expect? A review of 2-year radical prostatectomy specimen in a local hospital in Hong Kong. BJU Int. 2013;112(suppl 1):28. Abstract 30642. Koo Ha H. Predictive factors for locally advanced prostate cancer in prostate cancer patients with Gleason score of 6 or lower. BJU Int. 2013;112(suppl 1):16. Abstract 24978. Anderson J, Riciardelli L, Burney S, et al. Anxiety in men with prostate cancer treated by active surveillance. BJU Int. 2013;112(suppl 1):5. Abstract 22842. Gillatt D, Redaniel M, Wade J, et al. Waiting times from diagnosis to surgery and prostate cancer. BJU Int. 2013;112(suppl 1):20. Abstract 25562. Obertova Z, Scott N, Brown C, et al. Survival disparities between Māori and non-Māori men with non-localised prostate cancer in New Zealand. BJU Int. 2013;112(suppl 1):14. Abstract 24850. Smith D, Rodger J, Supramaniam R, et al. Treatment and survival outcomes for prostate cancer for Aboriginal men in New South Wales (NSW) Australia. BJU Int. 2013;112(suppl 1):10. Abstract 24710. Lawrenson R, Obertova Z, Hodgson F, et al. Screening for prostate cancer in rural men in New Zealand. BJU Int. 2013;112(suppl 1):14. Abstract 24858. Murphy D. Melbourne Consensus Statement on Prostate Cancer Testing. BJU Int. http://www.bjuinternational. com/bjui-blog/the-melbourne-consensus-statementon-prostate-cancer-testing/. Accessed 19 August 2013.
Vol. 15 No. 4 • 2013 • Reviews in Urology • 187
4004170006_RIU0599.indd 187
16/01/14 11:12 AM
Updates in the Care and Management of Prostate Cancer Highlights From the 2013 Prostate Cancer World Congress, August 6-10, 2013, Melbourne, Australia [ Rev Urol. 2013;15(4):185-187 doi: 10.3909/riu0599]
®
© 2014 MedReviews , LLC
KEY WORDS Active surveillance • Health disparities • Prostate cancer • Consensus statement • Pre-biopsy rectal swab
T
he Prostate Cancer World Congress (PCWC) was held in Melbourne, Australia, August 6-10, 2013, incorporating the 14th Australasian Prostate Cancer Congress. This meeting included more than 1000 delegates from around the world. There were three parallel streams for clinical urology, translational science, nursing/allied health, and general practice, with a total of 174 abstract presentations. Reviewed by Marnique Basto, Surgical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; Áine Goggins, Department of Medicine, Queen’s University, Belfast, UK; Stacy Loeb, MD, Department of Urology and Population Health, New York University and the Manhattan Veterans Affairs Hospital, New York, NY.
In the Clinical Urology program, prostate biopsy infections were an overarching theme following suit from the 2013 American Urological Association meeting held in San Diego, California. Indeed, numerous studies have raised concern about rising infectious complications after transrectal ultrasound (TRUS)–guided biopsy in the global setting of increasing antimicrobial resistance, leading to ongoing investigation into ways to reduce prostate biopsy risks.1 One strategy that has been recently investigated is the use of pre-biopsy rectal swab cultures. New data from Norris and colleagues found a 3.73% prevalence of extended spectrum B-lactamase (ESBL) carriage on pre-biopsy rectal swab in 53 patients from an Australian tertiary institution.2 Of interest, though, was that none of the 3.73% Vol. 15 No. 4 • 2013 • Reviews in Urology • 185
4004170006_RIU0599.indd 185
16/01/14 11:12 AM
Updates in the Management of Prostate Cancer continued of patients with infectious complications were noted to have ESBL carriage. Additional investigation is ongoing to determine whether pre-biopsy questionnaires can help identify the patients at greatest risk for antimicrobial resistance. In a prospective study of 124 men from New Zealand, Losco and Studd reported a zero sepsis rate in a high-risk cohort (n 5 62 men with previous TRUS or urosepsis, who were immunocompromised, or noted recent ciprofloxacin use or overseas travel) with the addition of ertapenem to standard prophylaxis.3 This compared with a 9.6% rate in low-risk patients (P 5 .03) who received the standard regimen of ciprofloxacin and amoxicillin. Of these, half grew ciprofloxacin-resistant organisms. Another large study by Leahy and colleagues that included 1937 patients from a single private Australian institution reported a 1.2% readmission rate for infection.4 They reported increasing use of carbapenems both as treatment for sepsis (58.7%) and for prophylaxis (8%), highlighting urologists’ concern over the increasing prevalence of multidrug-resistant bacteria. Although expanded antimicrobial prophylaxis is another possible way to reduce infections, a drawback to this approach is the potential for increased resistance in the future. Other studies evaluated the emerging role of transperineal template biopsy in Australia in reducing infectious complications and potentially improving cancer detection. Huang and colleagues suggested it be offered as an option for all repeat prostate biopsies given a zero sepsis rate and a 35% detection rate in those with a previously negative TRUS biopsy.5 Of these, 79% had anterior/transition zone tumors. Complications included
a 6.3% rate of acute urinary retention and a 2.7% rate of clot retention. Grummet and colleagues similarly reported a zero sepsis rate in a multi-institutional study in Victoria of 245 patients undergoing transperineal prostate biopsy.6 The authors concluded that, in the context of increasing multiresistant rectal flora, transperineal template biopsy is the preferred approach. However, most biopsies in Australia are already performed with anesthesia in the operating theater, so the translation of these findings to other settings where prostate biopsy is typically done in the outpatient clinic requires further investigation. Active surveillance (AS) was another key focus at the PCWC. Adoption rates of AS for low-risk prostate cancer in Australia are increasing, with recently published data from Victoria (2008-2011) reporting 40.6% uptake,7 which continues to expand. In a retrospective review of 409 patients, Satasivam and associates reported that 78% of low-risk men chose AS, with rapidly decreasing numbers undergoing radical prostatectomy, from 50% in late 2010 to 0% in 2013 (P 5 .009 for trend).8 However, concerns about the accuracy of pretreatment risk classification remain an issue. A study from Hong Kong sought to identify predictive factors for indolent disease at radical prostatectomy for those who met AS criteria.9 Only maximum percentage of cancer per core (, 50%) was associated with indolent disease at prostatectomy (P , .05). Because this variable is not currently included in the commonly used Prostate Cancer Research International Active Surveillance criteria, the authors suggested that it may be an important consideration for AS patient selection moving forward.
Another study of 161 low-risk patients from Korea found that the maximum core percentage of longest tumor (P 5 .002) and the percentage of positive cores (P 5 .019) were significant predictors of pathologic stage $ T3 disease.10 These combined findings suggest that biopsy core data are useful factors to consider when counseling patients about selection of treatment versus AS. An additional topic of discussion was the potential for anxiety among men choosing AS. However, Anderson and associates reported low levels of prostate cancer–related anxiety in the vast majority of patients (87%).11 This was likely attributable to the high levels of patient education reported by 92% of men in this study. Meanwhile, younger age and underlying anxiety traits were significant predictors for anxiety on AS and these patients may benefit from targeted education or more active therapy. Finally, another subject of controversy is whether short-term treatment delay could lead to a decrement in outcomes. A large UK study found no significant difference in survival rates between those who had surgery within 0 to 3 months versus 4 to 6 months after diagnosis,12 although additional long-term follow-up studies are important to further evaluate this issue. Another key theme at PCWC was health disparities between ethnic and sociodemographic groups. Winners of the Best Poster in Clinical Urology, Obertova and colleagues found that Māori men in New Zealand were more likely to have metastatic disease at diagnosis and were significantly more likely to die from prostate cancer than non-Māori men (HR, 2.95; 95% confidence interval [CI], 2.31-3.77).13 Similarly, Smith
186 • Vol. 15 No. 4 • 2013 • Reviews in Urology
4004170006_RIU0599.indd 186
16/01/14 11:12 AM
Updates in the Management of Prostate Cancer and colleagues reported that Aboriginal men in Australia had a 53% higher probability of death from prostate cancer at 5 years (17.5%; 95% CI, 12.4-23.3) compared with non-Aboriginal men (11.4%; 95% CI, 11.0-11.8).14 Finally, another New Zealand study observed lower prostate-specific antigen (PSA) screening rates in rural areas compared with main urban areas (17.6% vs 25.6%; P 5 .0001).15 Furthermore, PSA was more likely to be elevated at diagnosis in rural men (P 5 .0014). These studies demonstrate the need for additional measures to help bridge these health disparities. Undoubtedly, the major highlight of the meeting was the release of the Melbourne PSA Consensus Statement led by Dr. Declan Murphy, honorary clinical associate professor at the University of Melbourne and consultant urological surgeon at the Peter MacCallum Cancer Centre, along with an international faculty of world leaders in prostate cancer, including Tony Costello, Patrick Walsh, Thomas Ahlering, William Catalona, Oliver Sartor, Tom Pickles, Noel Clarke, Matthew Cooperberg, David Gillatt, Martin Gleave, Stacy Loeb, and Monique Roobol.16 In summary, the following recommendations were made: (1) for men aged 50 to 69 years, Level 1 evidence demonstrates that PSA testing reduces prostate cancer–specific
mortality and the incidence of metastatic prostate cancer; (2) prostate cancer diagnosis must be uncoupled from prostate cancer intervention; (3) PSA testing should not be considered on its own, but rather as part of a multivariable approach to early prostate cancer detection; (4) baseline PSA testing for men in their 40s is useful for predicting the future risk of prostate cancer; (5) older men in good health with over a 10-year life expectancy should not be denied PSA testing on the basis of their age. Overall, PSA remains a critical part of prostate cancer risk assessment that should be offered as part of a shared decision-making process. There is now definitive evidence demonstrating a diseasespecific mortality benefit with screening and it remains the only way to identify aggressive tumors in time for curative intervention. Conversely, many men with low-risk disease can be safely managed conservatively, highlighting the importance of dissociating diagnosis from treatment. The recommendations regarding the age to discontinue screening are also important considering that the average life expectancy of an Australian man at age 70 is 15 years. Given the many different prostate cancer guidelines currently in circulation, it is hoped that the Melbourne Consensus Statement will help bring clarity to these controversial issues.
References 1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
Loeb S, Vellekoop A, Ahmed HU, et al. Systematic review of complications of prostate biopsy. Eur Urol. 2013;64:876-892. Norris B, DeSousa T, Anderson P, Huang J. TRUS biopsy in the superbug era. Prevalence and predictors of ESBL carriage in an Australian tertiary hospital. BJU Int. 2013;112(suppl 1):25. Abstract 25762. Losco F, Studd R. Post-TRUS sepsis: targeted use of prophylactic ertapenem for high-risk patients. BJU Int. 2013;112(suppl 1):7. Abstract 4462. Leahy O, O’Reilly M, Phillips D, Grummet J. TRUS biopsy sepsis and use of carbapenem antibiotics at a single high volume local institution. BJU Int. 2013;112(suppl 1):26. Abstract 25802. Huang S, Reeves F, Preece J Grummet J. Transperineal template biopsy of the prostate: a review of the impact at Alfred Health. BJU Int. 2013;112(suppl 1):26. Abstract 25778. Grummet J, Weerakoon M, Huang S, et al. Sepsis and superbugs: should transperineal biopsy be offered to all prospective prostate biopsy patients? BJU Int. 2013;112(suppl 1):26. Abstract 25798. Evans SM, Millar JL, Wood JM, et al. Patterns of care for men diagnosed with prostate cancer in Victoria from 2008 to 2011. Med J Aust. 2013;198:540-545. Satasivam P, Vijayan S, Frydenberg M, Appu S. Contemporary management of prostate cancer at an Australian tertiary referral centre. BJU Int. 2013;112(suppl 1):17. Abstract 25094 Chan M, Yu C, Gheng C, Chu P. Be prepared for active surveillance. What should the patient and I expect? A review of 2-year radical prostatectomy specimen in a local hospital in Hong Kong. BJU Int. 2013;112(suppl 1):28. Abstract 30642. Koo Ha H. Predictive factors for locally advanced prostate cancer in prostate cancer patients with Gleason score of 6 or lower. BJU Int. 2013;112(suppl 1):16. Abstract 24978. Anderson J, Riciardelli L, Burney S, et al. Anxiety in men with prostate cancer treated by active surveillance. BJU Int. 2013;112(suppl 1):5. Abstract 22842. Gillatt D, Redaniel M, Wade J, et al. Waiting times from diagnosis to surgery and prostate cancer. BJU Int. 2013;112(suppl 1):20. Abstract 25562. Obertova Z, Scott N, Brown C, et al. Survival disparities between Māori and non-Māori men with non-localised prostate cancer in New Zealand. BJU Int. 2013;112(suppl 1):14. Abstract 24850. Smith D, Rodger J, Supramaniam R, et al. Treatment and survival outcomes for prostate cancer for Aboriginal men in New South Wales (NSW) Australia. BJU Int. 2013;112(suppl 1):10. Abstract 24710. Lawrenson R, Obertova Z, Hodgson F, et al. Screening for prostate cancer in rural men in New Zealand. BJU Int. 2013;112(suppl 1):14. Abstract 24858. Murphy D. Melbourne Consensus Statement on Prostate Cancer Testing. BJU Int. http://www.bjuinternational. com/bjui-blog/the-melbourne-consensus-statementon-prostate-cancer-testing/. Accessed 19 August 2013.
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