Is Comment Free? Ethical, editorial and political problems of
Editorial Comment
1
risk prostate cancer in the United States. J Natl Cancer Inst 2006; 98: 1134. 2. Cooperberg MR, Lubeck DP, Mehta SS and Carroll PR: Time trends in clinical risk stratification for prostate cancer: implications for outcomes (data from CaPSURE). J Urol 2003; 170: S21. 3. Carter HB, Walsh PC, Landis P and Epstein JI: Expectant management of nonpalpable prostate cancer with curative intent: preliminary results. J Urol 2002; 167: 1231. 4. Frankel S, Smith GD, Donovan J and Neal D: Screening for prostate cancer. Lancet 2003; 361: 1122. 5. Warlick C, Trock BJ, Landis P, Epstein JI and Carter HB: Delayed versus immediate surgical intervention and pros- tate cancer outcome. J Natl Cancer Inst 2006; 98: 355. 6. Klotz L: Active surveillance with selective delayed intervention for favorable risk prostate cancer. Urol Oncol 2006; 24: 46. 7. Patel MI, DeConcini DT, Lopez-Corona E, Ohori M, Wheeler T and Scardino PT: An analysis of men with clinically local- ized prostate cancer who deferred definitive therapy. J Urol 2004; 171: 1520. 8. Martin RM, Gunnell D, Hamdy F, Neal D, Lane A and Donovan J: Continuing controversy over monitoring men with localized prostate cancer: a systematic review of programs in the prostate specific antigen era. J Urol 2006; 176: 439. 9. Choo R, Klotz L, Danjoux C, Morton GC, DeBoer G, Szumacher E et al: Feasibility study: watchful waiting for localized low to intermediate grade prostate carcinoma with selective delayed intervention based on prostate specific antigen, histological and/or clinical progression J Urol 2002; 167: 1664. 10. Mohler JL, Williams BT and Freeman JA: Expectant manage- ment as an option for men with stage T1c prostate cancer: a preliminary study. World J Urol 1997; 15: 364. 11. Karakiewicz PI, Eastham JA, Graefen M, Cagiannos I, Stricker PD, Klein E et al: Prognostic impact of positive surgical margins in surgically treated prostate cancer: multi-institutional assessment of 5831 patients. Urology 2005; 66: 1245. EDITORIAL COMMENT Griffin et al report on the pathological findings of men undergoing radical prostatectomy for low volume Gleason 3 3 adenocarcinoma of the prostate, and demonstrate that approximately a third of patients who may have been poten- tial candidates for active surveillance will have adverse pathological features (reference 7 in article). 1 However, sev- eral critical issues should be raised when interpreting the data from this study. All retrospective radical prostatectomy series are influenced by selection bias as to which patients are offered and treated with radical prostatectomy. In addi- tion, an unknown number of patients in this study would not have been candidates for active surveillance without further evaluation because several men had pretreatment serum PSA greater than 10 ng/dl and inadequate pretreatment prostate biopsies with the total number of biopsy cores as low as 4. Lastly, no central pathological review was per- formed of the initial biopsy specimens, which may lead to upgrading in approximately 20% to 30% of cases, thereby further selecting patients who may not be appropriate can- didates for active surveillance. Thus, these data may not represent the true incidence of adverse pathological features in a cohort of currently selected active surveillance candi- dates. The question still remains as to how urologists appropri- ately and safely select patients for active surveillance pro- tocols, and when delayed definitive therapy should be im- plemented. To answer these questions requires a refined understanding of and development of pretreatment predic- tors for pathological and clinical outcomes, advances in ra- diological imaging, and novel molecular markers. Addition- ally, genetic and molecular studies may provide causative insight into the diverse biological differences in prostate tumorigenesis. Ultimately the therapeutic safety and effi- cacy of active surveillance protocols must be evaluated through well designed clinical trials with precise enrollment criteria and indications for definitive therapy. Brett S. Carver Department of Urology Memorial Sloan-Kettering Cancer Center New York, New York 1. Klotz L: Active surveillance for prostate cancer: for whom? J Clin Oncol 2005; 23: 8165. REPLY BY AUTHORS We agree that men with a PSA greater than 10 ng/ml are less likely to be considered as candidates for active monitor- ing. However, excluding these 13 patients from our analysis yielded similar results. That is, even among men with 1 or 2 cores of Gleason 3 3 prostate cancer and a PSA less than 10 ng/ml, 26% were upgraded and 7% had extracapsular tumor extension. Although there were a few patients who underwent a limited biopsy initially, the median number of biopsy cores was 11.3 and some men had up to 24 cores. Furthermore, this analysis includes a contemporary popu- lation (2003 to 2006), making the Will Rogers phenomenon less of a concern. That notwithstanding, despite the poten- tial pitfalls in evaluating upgrading, the 8% overall rate of extracapsular extension (7% for men with a PSA less than 10 ng/ml) is concerning for such a low risk group. It is noteworthy that Bastian et al similarly reported that non- organ confined disease was present in 8.4% of men who met the Epstein preoperative criteria for potentially insignifi- cant cancer (PSAD less than 0.15 ng/ml/gm, Gleason score 6 or less, fewer than 3 positive cores and 50% or less core involvement). 1 Overall these studies underscore the ongoing need for better preoperative markers of prostate cancer ag- gressiveness to safely defer definitive treatment. 1. Bastian PJ, Mangold LA, Epstein JI and Partin AW: Charac- teristics of insignificant clinical T1c prostate tumors. A con- temporary analysis. Cancer 2004; 101: 2001. SURGICAL OUTCOMES IN POTENTIAL ACTIVE MONITORING CANDIDATES 863
Transcript of Editorial Comment
risk prostate cancer in the United States. J Natl CancerInst 2006; 98: 1134.
2. Cooperberg MR, Lubeck DP, Mehta SS and Carroll PR: Timetrends in clinical risk stratification for prostate cancer:implications for outcomes (data from CaPSURE). J Urol2003; 170: S21.
3. Carter HB, Walsh PC, Landis P and Epstein JI: Expectantmanagement of nonpalpable prostate cancer with curativeintent: preliminary results. J Urol 2002; 167: 1231.
4. Frankel S, Smith GD, Donovan J and Neal D: Screening forprostate cancer. Lancet 2003; 361: 1122.
5. Warlick C, Trock BJ, Landis P, Epstein JI and Carter HB:Delayed versus immediate surgical intervention and pros-tate cancer outcome. J Natl Cancer Inst 2006; 98: 355.
6. Klotz L: Active surveillance with selective delayed interventionfor favorable risk prostate cancer. Urol Oncol 2006; 24: 46.
7. Patel MI, DeConcini DT, Lopez-Corona E, Ohori M, Wheeler Tand Scardino PT: An analysis of men with clinically local-ized prostate cancer who deferred definitive therapy. J Urol2004; 171: 1520.
8. Martin RM, Gunnell D, Hamdy F, Neal D, Lane A andDonovan J: Continuing controversy over monitoring menwith localized prostate cancer: a systematic review ofprograms in the prostate specific antigen era. J Urol2006; 176: 439.
9. Choo R, Klotz L, Danjoux C, Morton GC, DeBoer G, SzumacherE et al: Feasibility study: watchful waiting for localized lowto intermediate grade prostate carcinoma with selectivedelayed intervention based on prostate specific antigen,histological and/or clinical progression J Urol 2002; 167:1664.
10. Mohler JL, Williams BT and Freeman JA: Expectant manage-ment as an option for men with stage T1c prostate cancer:a preliminary study. World J Urol 1997; 15: 364.
11. Karakiewicz PI, Eastham JA, Graefen M, Cagiannos I,Stricker PD, Klein E et al: Prognostic impact of positivesurgical margins in surgically treated prostate cancer:multi-institutional assessment of 5831 patients. Urology2005; 66: 1245.
EDITORIAL COMMENT
Griffin et al report on the pathological findings of menundergoing radical prostatectomy for low volume Gleason3 � 3 adenocarcinoma of the prostate, and demonstrate thatapproximately a third of patients who may have been poten-tial candidates for active surveillance will have adversepathological features (reference 7 in article).1 However, sev-eral critical issues should be raised when interpreting thedata from this study. All retrospective radical prostatectomyseries are influenced by selection bias as to which patientsare offered and treated with radical prostatectomy. In addi-tion, an unknown number of patients in this study would nothave been candidates for active surveillance without furtherevaluation because several men had pretreatment serumPSA greater than 10 ng/dl and inadequate pretreatmentprostate biopsies with the total number of biopsy cores aslow as 4. Lastly, no central pathological review was per-formed of the initial biopsy specimens, which may lead to
upgrading in approximately 20% to 30% of cases, therebyfurther selecting patients who may not be appropriate can-didates for active surveillance. Thus, these data may notrepresent the true incidence of adverse pathological featuresin a cohort of currently selected active surveillance candi-dates.
The question still remains as to how urologists appropri-ately and safely select patients for active surveillance pro-tocols, and when delayed definitive therapy should be im-plemented. To answer these questions requires a refinedunderstanding of and development of pretreatment predic-tors for pathological and clinical outcomes, advances in ra-diological imaging, and novel molecular markers. Addition-ally, genetic and molecular studies may provide causativeinsight into the diverse biological differences in prostatetumorigenesis. Ultimately the therapeutic safety and effi-cacy of active surveillance protocols must be evaluatedthrough well designed clinical trials with precise enrollmentcriteria and indications for definitive therapy.
Brett S. CarverDepartment of Urology
Memorial Sloan-Kettering Cancer CenterNew York, New York
1. Klotz L: Active surveillance for prostate cancer: for whom?J Clin Oncol 2005; 23: 8165.
REPLY BY AUTHORS
We agree that men with a PSA greater than 10 ng/ml areless likely to be considered as candidates for active monitor-ing. However, excluding these 13 patients from our analysisyielded similar results. That is, even among men with 1 or 2cores of Gleason 3 � 3 prostate cancer and a PSA less than10 ng/ml, 26% were upgraded and 7% had extracapsulartumor extension. Although there were a few patients whounderwent a limited biopsy initially, the median number ofbiopsy cores was 11.3 and some men had up to 24 cores.Furthermore, this analysis includes a contemporary popu-lation (2003 to 2006), making the Will Rogers phenomenonless of a concern. That notwithstanding, despite the poten-tial pitfalls in evaluating upgrading, the 8% overall rate ofextracapsular extension (7% for men with a PSA less than10 ng/ml) is concerning for such a low risk group. It isnoteworthy that Bastian et al similarly reported that non-organ confined disease was present in 8.4% of men who metthe Epstein preoperative criteria for potentially insignifi-cant cancer (PSAD less than 0.15 ng/ml/gm, Gleason score 6or less, fewer than 3 positive cores and 50% or less coreinvolvement).1 Overall these studies underscore the ongoingneed for better preoperative markers of prostate cancer ag-gressiveness to safely defer definitive treatment.
1. Bastian PJ, Mangold LA, Epstein JI and Partin AW: Charac-teristics of insignificant clinical T1c prostate tumors. A con-temporary analysis. Cancer 2004; 101: 2001.
SURGICAL OUTCOMES IN POTENTIAL ACTIVE MONITORING CANDIDATES 863
