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Re: Focal Therapy for Localised Unifocal and Multifocal Prostate Cancer: A Prospective Development Study
1768
PROSTATE CANCER
Re: Prostate-Specific Antigen Concentration in Young Men: New Estimates and Review of the Literature S. Sutcliffe, R. Pakpahan, L. J. Sokoll, D. J. Elliott, R. L. Nevin, S. B. Cersovsky, P. C. Walsh and E. A. Platz Department of Surgery, Division of Public Health Sciences, Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health and Department of Pathology, James Buchanan Brady Urological Institute and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore and U. S. Army Institute of Public Health, U. S. Army Public Health Command (Provisional), Aberdeen Proving Ground, Aberdeen, Maryland, and Department of Preventive Medicine, Bayne-Jones Army Community Hospital, Fort Polk, Louisiana BJU Int 2012; Epub ahead of print.
Objective: To provide race-specific prostate-specific antigen (PSA) reference distributions for young men less than 40 years of age who might have undergone non-recommended PSA testing because of their family history of prostate cancer or inadvertently as part of a standard panel of tests. Materials and Methods: We used data from a large existing study of young, male Caucasian- and AfricanAmerican members of the US military with stored serum in the Department of Defense serum repository. As part of this previous study, we selected a random sample of 373 Caucasian- and 366 African-American men aged 28 –36 years with an archived serum specimen collected for standard military purposes from 2004 to 2006. We measured serum total PSA concentration in this specimen using the Beckman Coulter Access Hybritech PSA assay. Results: The PSA level ranged from ⬍0.01 to 3.34 ng/mL among Caucasian-American men, with a median of 0.56 ng/mL and a 95th percentile of 1.42 ng/mL. The PSA level ranged from 0.12 to 6.45 ng/mL among African-American men, with a median of 0.64 ng/mL and 95th percentile of 1.89 ng/mL. The PSA level was significantly higher in African- than in Caucasian-American men (P ⫽ 0.001). Conclusion: The PSA estimates, together with those summarized from the literature, provide age- and race-specific PSA reference distributions for young men who might have undergone non-recommended PSA testing. Comparisons by race could also begin to inform the timing of divergence of prostate cancer risk by race. Editorial Comment: This article provides an important reference that may be useful under unusual circumstances. I was prompted to look into this problem when a patient of mine who was diagnosed with prostate cancer in his early 40s told me that his 21-year-old son had a PSA of 1.2. I knew offhand that the median PSA for men in their 40s was 0.6, and thus I was alarmed by this finding. However, the information in this article is reassuring. For men in their 20s and 30s the median PSA is also around 0.6 with very little variation. Why? Because prostate size for men beginning at age 20 and going through age 40 is relatively stable at around 20 cc.1 It remains to be seen whether men in their 20s who have high PSA levels, like the patient I mentioned, will eventually be shown to be at increased risk for developing cancer. Patrick C. Walsh, M.D. 1. Berry SJ, Coffey DS, Walsh PC et al: The development of human benign prostatic hyperplasia with age. J Urol 1984; 132: 474.
Re: Focal Therapy for Localised Unifocal and Multifocal Prostate Cancer: A Prospective Development Study H. U. Ahmed, R. G. Hindley, L. Dickinson, A. Freeman, A. P. Kirkham, M. Sahu, R. Scott, C. Allen, J. Van der Meulen and M. Emberton Division of Surgery and Interventional Science, University College London and Department of Urology, University College London Hospitals NHS Foundation Trust, London, United Kingdom Lancet Oncol 2012; 13: 622– 632.
Background: Radical whole-gland therapy can lead to significant genitourinary and rectal side-effects for men with localised prostate cancer. We report on whether selective focal ablation of unifocal and multifocal cancer lesions can reduce this treatment burden. Methods: Men aged 45– 80 years were eligible for this prospective development study if they had low-risk to high-risk localised prostate
PROSTATE CANCER
1769
cancer (prostate specific antigen [PSA] ⱕ15 ng/mL, Gleason score ⱕ4 ⫹ 3, stage ⱕT2), with no previous androgen deprivation or treatment for prostate cancer, and who could safely undergo multiparametric MRI and have a general anaesthetic. Patients received focal therapy using highintensity focused ultrasound, delivered to all known cancer lesions, with a margin of normal tissue, identified on multiparametric MRI, template prostate-mapping biopsies, or both. Primary endpoints were adverse events (serious and otherwise) and urinary symptoms and erectile function assessed using patient questionnaires. Analyses were done on a per-protocol basis. Findings: 42 men were recruited between June 27, 2007, and June 30, 2010; one man died from an unrelated cause (pneumonia) 3 months after treatment and was excluded from analyses. After treatment, one man was admitted to hospital for acute urinary retention, and another had stricture interventions requiring hospital admission. Nine men (22%, 95% CI 11–38) had self-resolving, mild to moderate, intermittent dysuria (median duration 5䡠0 days [IQR 2䡠5–18䡠5]). Urinary debris occurred in 14 men (34%, 95% CI 20 –51), with a median duration of 14䡠5 days (IQR 6䡠0 –16䡠5). Urinary tract infection was noted in seven men (17%, 95% CI 7–32). Median overall International Index of Erectile Function-15 (IIEF-15) scores were similar at baseline and at 12 months (p ⫽ 0䡠060), as were median IIEF-15 scores for intercourse satisfaction (p ⫽ 0䡠454), sexual desire (p ⫽ 0䡠644), and overall satisfaction (p ⫽ 0䡠257). Significant deteriorations between baseline and 12 months were noted for IIEF-15 erectile (p ⫽ 0䡠042) and orgasmic function (p ⫽ 0䡠003). Of 35 men with good baseline function, 31 (89%, 95% CI 73–97) had erections sufficient for penetration 12 months after focal therapy. Median UCLA Expanded Prostate Cancer Index Composite (EPIC) urinary incontinence scores were similar at baseline as and 12 months (p ⫽ 0䡠045). There was an improvement in lower urinary tract symptoms, assessed by International Prostate Symptom Score (IPSS), between baseline and 12 months (p ⫽ 0䡠026), but the IPSS-quality of life score showed no difference between baseline and 12 months (p ⫽ 0䡠655). All 38 men with no baseline urinary incontinence were leak-free and pad-free by 9 months. All 40 men pad-free at baseline were pad-free by 3 months and maintained pad-free continence at 12 months. No significant difference was reported in median Trial Outcomes Index scores between baseline and 12 months (p ⫽ 0䡠113) but significant improvement was shown in median Functional Assessment of Cancer Therapy (FACT)-Prostate (p ⫽ 0䡠045) and median FACT-General scores (p ⫽ 0䡠041). No histological evidence of cancer was identified in 30 of 39 men biopsied at 6 months (77%, 95% CI 61– 89); 36 (92%, 79 –98) were free of clinically significant cancer. After retreatment in four men, 39 of 41 (95%, 95% CI 83–99) had no evidence of disease on multiparametric MRI at 12 months. Interpretation: Focal therapy of individual prostate cancer lesions, whether multifocal or unifocal, leads to a low rate of genitourinary side-effects and an encouraging rate of early absence of clinically significant prostate cancer. Editorial Comment: This study looks at the use of high intensity focused ultrasound to deliver focal treatment of all known cancer lesions with a margin of normal tissue. These lesions were identified on multiparametric magnetic resonance imaging, template prostate mapping biopsies or both. Bloomberg Businessweek summarized the results with this exalting endorsement: “None of the 41 men in the trial reported urine incontinence and only one in 10 suffered from poor erections 12 months after the treatment . . . About 95% of the men were cancer-free after a year, meaning most had a ‘perfect outcome’ in terms of disease progression and side effects. . ..”1 As soon as I saw this report, I rushed to read the paper to determine how they proved these patients were cancer-free 12 months following surgery. I learned that the definition of “cancer-free” was “no evidence of clinically significant disease at 12 months on multiparametric MRI.” It is disappointing that a Lancet journal would permit authors to conclude that these patients were actually free of clinically significant cancer and for the authors to fool the public into believing it. Patrick C. Walsh, M.D. 1. Connolly A: Ultrasound may permit prostate lumpectomies, study says. Available at http://www.bloomberg.com/news/2012-04-16/ultrasound-may-permitprostate-lumpectomies-study-says.html. Accessed June 12, 2012.
PROSTATE CANCER
Re: Prostate-Specific Antigen Concentration in Young Men: New Estimates and Review of the Literature S. Sutcliffe, R. Pakpahan, L. J. Sokoll, D. J. Elliott, R. L. Nevin, S. B. Cersovsky, P. C. Walsh and E. A. Platz Department of Surgery, Division of Public Health Sciences, Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health and Department of Pathology, James Buchanan Brady Urological Institute and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore and U. S. Army Institute of Public Health, U. S. Army Public Health Command (Provisional), Aberdeen Proving Ground, Aberdeen, Maryland, and Department of Preventive Medicine, Bayne-Jones Army Community Hospital, Fort Polk, Louisiana BJU Int 2012; Epub ahead of print.
Objective: To provide race-specific prostate-specific antigen (PSA) reference distributions for young men less than 40 years of age who might have undergone non-recommended PSA testing because of their family history of prostate cancer or inadvertently as part of a standard panel of tests. Materials and Methods: We used data from a large existing study of young, male Caucasian- and AfricanAmerican members of the US military with stored serum in the Department of Defense serum repository. As part of this previous study, we selected a random sample of 373 Caucasian- and 366 African-American men aged 28 –36 years with an archived serum specimen collected for standard military purposes from 2004 to 2006. We measured serum total PSA concentration in this specimen using the Beckman Coulter Access Hybritech PSA assay. Results: The PSA level ranged from ⬍0.01 to 3.34 ng/mL among Caucasian-American men, with a median of 0.56 ng/mL and a 95th percentile of 1.42 ng/mL. The PSA level ranged from 0.12 to 6.45 ng/mL among African-American men, with a median of 0.64 ng/mL and 95th percentile of 1.89 ng/mL. The PSA level was significantly higher in African- than in Caucasian-American men (P ⫽ 0.001). Conclusion: The PSA estimates, together with those summarized from the literature, provide age- and race-specific PSA reference distributions for young men who might have undergone non-recommended PSA testing. Comparisons by race could also begin to inform the timing of divergence of prostate cancer risk by race. Editorial Comment: This article provides an important reference that may be useful under unusual circumstances. I was prompted to look into this problem when a patient of mine who was diagnosed with prostate cancer in his early 40s told me that his 21-year-old son had a PSA of 1.2. I knew offhand that the median PSA for men in their 40s was 0.6, and thus I was alarmed by this finding. However, the information in this article is reassuring. For men in their 20s and 30s the median PSA is also around 0.6 with very little variation. Why? Because prostate size for men beginning at age 20 and going through age 40 is relatively stable at around 20 cc.1 It remains to be seen whether men in their 20s who have high PSA levels, like the patient I mentioned, will eventually be shown to be at increased risk for developing cancer. Patrick C. Walsh, M.D. 1. Berry SJ, Coffey DS, Walsh PC et al: The development of human benign prostatic hyperplasia with age. J Urol 1984; 132: 474.
Re: Focal Therapy for Localised Unifocal and Multifocal Prostate Cancer: A Prospective Development Study H. U. Ahmed, R. G. Hindley, L. Dickinson, A. Freeman, A. P. Kirkham, M. Sahu, R. Scott, C. Allen, J. Van der Meulen and M. Emberton Division of Surgery and Interventional Science, University College London and Department of Urology, University College London Hospitals NHS Foundation Trust, London, United Kingdom Lancet Oncol 2012; 13: 622– 632.
Background: Radical whole-gland therapy can lead to significant genitourinary and rectal side-effects for men with localised prostate cancer. We report on whether selective focal ablation of unifocal and multifocal cancer lesions can reduce this treatment burden. Methods: Men aged 45– 80 years were eligible for this prospective development study if they had low-risk to high-risk localised prostate
PROSTATE CANCER
1769
cancer (prostate specific antigen [PSA] ⱕ15 ng/mL, Gleason score ⱕ4 ⫹ 3, stage ⱕT2), with no previous androgen deprivation or treatment for prostate cancer, and who could safely undergo multiparametric MRI and have a general anaesthetic. Patients received focal therapy using highintensity focused ultrasound, delivered to all known cancer lesions, with a margin of normal tissue, identified on multiparametric MRI, template prostate-mapping biopsies, or both. Primary endpoints were adverse events (serious and otherwise) and urinary symptoms and erectile function assessed using patient questionnaires. Analyses were done on a per-protocol basis. Findings: 42 men were recruited between June 27, 2007, and June 30, 2010; one man died from an unrelated cause (pneumonia) 3 months after treatment and was excluded from analyses. After treatment, one man was admitted to hospital for acute urinary retention, and another had stricture interventions requiring hospital admission. Nine men (22%, 95% CI 11–38) had self-resolving, mild to moderate, intermittent dysuria (median duration 5䡠0 days [IQR 2䡠5–18䡠5]). Urinary debris occurred in 14 men (34%, 95% CI 20 –51), with a median duration of 14䡠5 days (IQR 6䡠0 –16䡠5). Urinary tract infection was noted in seven men (17%, 95% CI 7–32). Median overall International Index of Erectile Function-15 (IIEF-15) scores were similar at baseline and at 12 months (p ⫽ 0䡠060), as were median IIEF-15 scores for intercourse satisfaction (p ⫽ 0䡠454), sexual desire (p ⫽ 0䡠644), and overall satisfaction (p ⫽ 0䡠257). Significant deteriorations between baseline and 12 months were noted for IIEF-15 erectile (p ⫽ 0䡠042) and orgasmic function (p ⫽ 0䡠003). Of 35 men with good baseline function, 31 (89%, 95% CI 73–97) had erections sufficient for penetration 12 months after focal therapy. Median UCLA Expanded Prostate Cancer Index Composite (EPIC) urinary incontinence scores were similar at baseline as and 12 months (p ⫽ 0䡠045). There was an improvement in lower urinary tract symptoms, assessed by International Prostate Symptom Score (IPSS), between baseline and 12 months (p ⫽ 0䡠026), but the IPSS-quality of life score showed no difference between baseline and 12 months (p ⫽ 0䡠655). All 38 men with no baseline urinary incontinence were leak-free and pad-free by 9 months. All 40 men pad-free at baseline were pad-free by 3 months and maintained pad-free continence at 12 months. No significant difference was reported in median Trial Outcomes Index scores between baseline and 12 months (p ⫽ 0䡠113) but significant improvement was shown in median Functional Assessment of Cancer Therapy (FACT)-Prostate (p ⫽ 0䡠045) and median FACT-General scores (p ⫽ 0䡠041). No histological evidence of cancer was identified in 30 of 39 men biopsied at 6 months (77%, 95% CI 61– 89); 36 (92%, 79 –98) were free of clinically significant cancer. After retreatment in four men, 39 of 41 (95%, 95% CI 83–99) had no evidence of disease on multiparametric MRI at 12 months. Interpretation: Focal therapy of individual prostate cancer lesions, whether multifocal or unifocal, leads to a low rate of genitourinary side-effects and an encouraging rate of early absence of clinically significant prostate cancer. Editorial Comment: This study looks at the use of high intensity focused ultrasound to deliver focal treatment of all known cancer lesions with a margin of normal tissue. These lesions were identified on multiparametric magnetic resonance imaging, template prostate mapping biopsies or both. Bloomberg Businessweek summarized the results with this exalting endorsement: “None of the 41 men in the trial reported urine incontinence and only one in 10 suffered from poor erections 12 months after the treatment . . . About 95% of the men were cancer-free after a year, meaning most had a ‘perfect outcome’ in terms of disease progression and side effects. . ..”1 As soon as I saw this report, I rushed to read the paper to determine how they proved these patients were cancer-free 12 months following surgery. I learned that the definition of “cancer-free” was “no evidence of clinically significant disease at 12 months on multiparametric MRI.” It is disappointing that a Lancet journal would permit authors to conclude that these patients were actually free of clinically significant cancer and for the authors to fool the public into believing it. Patrick C. Walsh, M.D. 1. Connolly A: Ultrasound may permit prostate lumpectomies, study says. Available at http://www.bloomberg.com/news/2012-04-16/ultrasound-may-permitprostate-lumpectomies-study-says.html. Accessed June 12, 2012.