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6. Klotz L: Active surveillance with selective delayedintervention for favorable risk prostate cancer. Urol

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REFERENCES

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7. Whitmore WF Jr: Natural history of low-stageprostatic cancer and the impact of early detection.

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8. Schroder FH, Hugosson J, Roobol MJ et al: Screeningand prostate-cancer mortality in a randomized Euro-

Oncol 2006; 24: 46. Urol Clin North Am 1990; 17: 689. pean study. N Engl J Med 2009; 360: 1320.

The statement that “less than two-thirds [of men]receiving delayed treatment after progression onsurveillance had organ confined disease” is mislead-ing. Depending on tumor grade, many tumors withEPE are still likely to be cured. For example, GS 6tumors with focal EPE have a 5-year biochemicalprogression-free rate almost identical to that seenwith organ confined cancers of the same grade.1 Oneneeds to make a distinction between the Universityof Toronto program described by Klotz (reference 6in comment), which allows men with GS 7 cancer tobe followed expectantly, and most other active sur-veillance programs, including our own, which wouldtypically recommend immediate definitive therapyfor men with this biopsy finding.

According to Catalona as long as preoperativeprediction of potentially insignificant cancer is notperfect, all men should be offered the benefit of im-mediate definitive therapy. This all or none ap-proach ignores the problem that in the UnitedStates many radical prostatectomies are performedfor limited disease that in retrospect likely couldhave been followed expectantly. For example, as of1997 between 26% and 29% of all prostate cancerstreated by radical prostatectomy at our institutionwere potentially insignificant, organ confined can-cers less than 0.5 cc with no GP 4 (reference 5 inarticle).2 This incidence has increased even furtherduring the last 10 years with lower PSA cut points totrigger prostate biopsy. Furthermore, in approxi-mately 5% of our RP cases pathologists have diffi-culty even identifying tumor.3 Surgeons are rela-tively isolated from these issues compared topathologists who weekly review cases with minimallow grade tumor. In addition, most radical prosta-tectomies in the United States are not performed athigh volume centers by high volume surgeons and,thus, the morbidity of surgical intervention cannot

We have been formally studying the preoperativeidentification of potentially insignificant prostatecancer to improve our predictive abilities. In ourinitial studies we recognized that the potential forunder recognizing more extensive or higher gradecancer was in part related to under sampling of theprostate. Based on these studies we changed ourselection criteria to require at least a 12-core sam-pling of the prostate at enrollment. Further studieshave shown that PSA and its derivative measure-ments have not been sufficiently predictive for theindividual patient, such that we continue to requireroutine followup prostate needle biopsies to assessfor progression (reference 7 in article). In the cur-rent study almost all large tumors were located an-teriorly at progression. Based on these findings wehave modified our surveillance biopsy protocol toinclude sampling of the anterior aspect of the pros-tate, particularly the transition zone.

While we recognize that there has been a learningcurve with this process, we are making strides tobetter select men who are candidates for active sur-veillance. Our approach with yearly biopsies recog-nizes the potential for future tumor growth andsampling error, and our data show that, with un-common exception, delayed definitive therapy inmen under active surveillance does not significantlyworsen the chance for cure. With careful selectionand improvements to our active surveillance proto-col, patients with low risk prostate cancer can bemonitored in a more effective manner while avoidingthe morbidity associated with cancer treatments.However, even with these modifications we realizethat as with anything in medicine, our specificityfor identifying potentially insignificant cancer willnever be 100%. Consequently we counsel men con-sidering active surveillance on the risk of progres-

be ignored. sion and the likelihood of cure if progression occurs.

1. Epstein JI, Carmichael M, Pizov G et al: Influenceof capsular penetration on progression followingradical prostatectomy: a study of 196 cases with

2. Carter HB, Sauvageot J, Walsh PC et al: Pro-spective evaluation of men with stage T1c ad-enocarcinoma of the prostate. J Urol 1997; 157:

3. DiGiuseppe JA, Sauvageot J and Epstein JI: In-creasing incidence of minimal residual cancer rad-ical prostatectomy specimens. Am J Surg Pathol

1997; 21: 174.