European Urology

4. Discussion

Today, clinicians recognize that a growing number of cancers detected by PSA screening are likely to be LRPC and may never be life-threatening during the patient's lifetime. Nevertheless, LRPC patients are often subjected to treatment and its HRQoL consequences without bettering their chances for progression-free survival (PFS) [14] x S. Roemeling, M.J. Roobol, M.W. Kattan, T.H. van der Kwast, E.W. Steyerberg, F.H. Schroder. Nomogram use for the prediction of indolent prostate cancer: impact on screen-detected populations. Cancer. 2007;110:2218-2221 Crossref. .

Although the percentage of patients who have treatment for LRPC after initial AS ranges from 17% to 33%, no markers accurately define which tumors “progress”[15] x R.M. Martin, D. Gunnell, F. Hamdy, D. Neal, A. Lane, J. Donovan. Continuing controversy over monitoring men with localized prostate cancer: a systematic review of programs in the prostate specific antigen era. J Urol. 2006;176:439-449 Crossref. . There is concern among urologists that tumors, while being monitored, may progress beyond the opportunity for cure. Ploussard et al suggested that PCa patients initially diagnosed by a 21-core biopsy who then select AS had a higher likelihood of more favorable disease on TP [16] x G. Ploussard, E. Xylinas, L. Salomon, et al. The role of biopsy core number in selecting prostate cancer patients for active surveillance. Eur Urol. 2009;56:891-898 Abstract, Full-text, PDF, Crossref. . Others have argued, though, that men diagnosed based on a more limited initial biopsy have also demonstrated favorable outcomes at treatment following AS [17] x R.C.N. van den Bergh, S. Roemeling, M.J. Roobol, et al. Outcomes of men with screen-detected prostate cancer eligible for active surveillance who were managed expectantly. Eur Urol. 2009;55:1-8 Abstract, Full-text, PDF, Crossref. .

Several critical factors should have influenced support of AS. Change in the technique of prostate biopsies and increased numbers of cores obtained have moderated grade migration on the surgical specimen. Over the past 15 yr, we found 20% fewer (from 47% to 27%) “under-graded” tumors than previously observed [18] x A. Rajinikanth, M. Manoharan, C.T. Soloway, F.J. Civantos, M.S. Soloway. Trends in Gleason score: concordance between biopsy and prostatectomy over 15 years. Urology. 2008;72:177-182 Crossref. .

By carefully selecting the AS cohort to include only those patients who have been compliant with the guidelines of close surveillance and who have low-volume disease (≤20% of tumor in two or fewer cores), a relatively small percentage (14% in this cohort) have required treatment. Among those eventually treated with surgery or RT, no patient has progressed or died from PCa. Progression was defined as BCR. In the AS cohort treated with TP (12 of 32), tumor volume ≤20% was reported in 100% of the patients and a positive margin in 3 of 12 patients. All patients were free of SVI, and one patient had EPE (Fig. 1).

As in other reported studies 19 x F.H. Schröder, M.J. Roobol, T.H. van der Kwast, R. Kranse, C.H. Bangma. Does PSA velocity predict prostate cancer in pre-screened populations?. Eur Urol. 2006;49:460-465 discussion 465 , and 20 x M.F. O’Brien, A.M. Cronin, P.A. Fearn, et al. Pretreatment prostate-specific antigen (PSA) velocity and doubling time are associated with outcome but neither improves prediction of outcome beyond pretreatment PSA alone in patients treated with radical prostatectomy. J Clin Oncol. 2009;27:3591-3597 Crossref. , neither PSA DT nor PSA velocity was an indication for treatment in our cohort. Increase in Gleason score or tumor volume was the threshold to urge treatment. Even though our mean post-TP follow-up is only 27 mo (range: 2–47; median: 35), we are cautiously optimistic that the prognosis will likely be as good as those with initial TP. Change in clinical stage coupled with a rising PSA level triggered treatment in older patients (>80 yr of age after being followed) who elected HT. Only one patient elected treatment because of distress over living with untreated PCa.

Waning sexual function may be a common disease-specific concern for patients with PCa 21 x A.R. Helgason, J. Adolfsson, P. Dickman, M. Fredrikson, S. Arver, G. Steineck. Waning sexual function—the most important disease-specific distress for patients with prostate cancer. Br J Cancer. 1996;73:1417-1421 , and 22 x M.S. Soloway, C.T. Soloway, S. Williams, R. Ayyathurai, B. Kava, M. Manoharan. Active surveillance; a reasonable management alternative for patients with prostate cancer: the Miami experience. BJU Int. 2008;101:165-169 . Beginning in 2007, all men with a diagnosis of PCa were asked to complete the SHIM. Of this subset of our AS cohort, 44% (first SHIM) and 56% (last SHIM) had at least moderate (≤16) ED. The significant increase in ED was seen in three of four age groups. The median follow-up was <3 yr; thus, age may not be the significant factor that affects ED in this AS cohort (Table 3).

Why are few men offered AS, and of those patients who are, why do so few choose it as an alternate strategy? There appears to be a lack of acceptance for AS [23] x K.S. Tseng, P. Landis, J.I. Epstein, B.J. Trock, H.B. Carter. Risk stratification of men choosing surveillance for low risk prostate cancer. J Urol. 2010;183:1779-1785 Crossref. . In a study of 110 of our AS cohort, 67% reported that the physician who diagnosed their PCa did not offer AS as an alternative to treatment. This offer is critical because it was reported that as many as 57–70% of patients chose treatment based on physician recommendation [24] x S.B. Zeliadt, S.D. Ramsey, D.F. Penson, et al. Why do men choose one treatment over another?: a review of patient decision making for localized prostate cancer. Cancer. 2006;106:1865-1874 Crossref. .

Before PSA screening, nearly half of PCa patients were diagnosed with advanced disease (T3–T4) [10] x A.V. D’Amico, R. Whittington, S.B. Malkowicz, et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA. 1998;280:969-974 Crossref. and had a poor prognosis. The problem, therefore, is not in diagnosing PCa but in educating patients about risk-adapted alternatives. Patients have the right to know they have LRPC, and physicians should not feel compelled to treat every PCa patient. With comprehensive educational information and supportive care from the physician, as many as 45% of PCa patients could postpone treatment—maybe indefinitely [1] x H. O’Donnell, C. Parker. What is low-risk prostate cancer and what is its natural history?. World J Urol. 2008;26:415-422 Crossref. .

Our study has some limitations. AS patients with no ED were evaluated to see whether repeated biopsies might alter erectile function, as suggested by Fujita et al [25] x K. Fujita, P. Landis, B.K. McNeil, C.P. Pavlovich. Serial prostate biopsies are associated with an increased risk of erectile dysfunction in men with prostate cancer on active surveillance. J Urol. 2009;182:2664-2669 Crossref. . Because we only started collecting data on QoL objectively in 2007, we are lacking sufficient data to draw conclusions because of the short time span and the small number of repeated biopsies between the first and last questionnaire. Another limitation of our study is the small number of patients treated with TP. A larger number of patients treated and longer follow-up are essential to better define the outcome of treatment following AS. Merging the data from multiple institutions might provide the most accurate outcome of treated AS patients.