ARE THE NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE GUIDELINES THAT PROMULGATE ACTIVE SURVEILLANCE FOR LOW-RISK PROSTATE CANCER JUSTIFIED BY THE AVAILABLE EVIDENCE?

Authors


Roger Kirby, The Prostate Centre, 32 Wimpole Street London W1G 8GT, UK.
e-mail: bjui@theprostatecentre.com

Abbreviations
NICE

National Institute for Health and Clinical Excellence

AS

active surveillance

RP

radical prostatectomy.

INTRODUCTION

Very recently, guidelines for the management of localized prostate cancer were issued by the National Institute for Health and Clinical Excellence (NICE) in the UK (http://www.nice.org.uk/guidance/index.jsp?action=byID&o=11924). Although sensible in many respects, they have emphasized the role of active surveillance (AS) for men with so called ‘low-risk’ prostate cancer. However, can we really define with certainty the men with ‘indolent’ cancers that have a minimal risk of progression? Moreover, can we truly recognize that progression is occurring at a time when the situation is still remediable?

The parameters of so-called ‘low-risk’ prostate cancers best managed by active surveillance include a presenting PSA level of <10 ng/mL, a Gleason score of ≤6, and no disease being palpable on a DRE [1]. Others have suggested protocols for AS; most include the number and percentage of cores involved by cancer, and a 3-monthly DRE and PSA determination, followed by a repeat TRUS-guided biopsy of the prostate and MRI at 1 year [2,3]. Provided that there is no evidence of progression of the cancer at that stage, the surveillance protocol is relaxed to 6-monthly follow-ups with a further biopsy at 3–5 years. Currently, there is little to suggest that men managed in this way suffer psychologically [4].

However, a note of caution comes from a recent study by Harnden et al.[5], who report a meta-analysis on whether patients with microfocal prostate cancer on biopsy have adverse pathological findings or any significant risk of PSA recurrence after undergoing radical prostatectomy (RP). In all, 238 articles were carefully evaluated by this group and in the final review, 29 articles addressed the specific question of the correlation between small-volume cancer on biopsy and pathological findings, biochemical or clinical progression, or mortality. Where possible, outcome data were pooled to estimate the overall risk associated with small-volume cancer at biopsy. A fixed-effect model was used if there was no evidence of heterogeneity. If heterogeneity was evident, then a random-effects model was used.

All the studies were retrospective and none randomized. Studies varied in the maximum number of biopsy cores that were allowed to qualify for the definition of microfocal prostate cancer, and whether the maximum length of cancer and highest Gleason score were specified. The most common values adopted were a single positive core and a threshold of 3 mm for the prostate cancer length. The occurrence rate of no cancer in the RP specimen (‘disappearing cancer’) was 0.8%. The overall estimate of the risk that patients with microfocal prostate cancer would have extracapsular extension at RP was 17.6%. The combined estimate for a positive surgical margin among men with microfocal prostate cancer was 12%. The range of PSA recurrences among this population was 0–26%, with an estimated risk of 8.6%. Among studies of watchful waiting, an increasing PSA level was reported in nine of 15 patients who had a microfocus of prostate cancer. There was conversion to definitive therapy in 30%. The overall conclusion was that a small volume of prostate cancer in prostatic biopsies is not necessarily indicative of a good prognosis.

Further important questions about the promulgation of AS as a management strategy for prostate cancer are raised by a recent publication of a study of prostate cancer mortality in the USA and UK in 1975–2004 [6]. This report highlights the four-fold greater decline in prostate cancer mortality in the USA compared with the UK since 1992. This period coincides with a much greater uptake of PSA screening in the USA; in 2001, 57% of men in America aged ≥50 years reported having a PSA test within the previous year [6]; by contrast in the UK, only 6% of men aged 45–84 years were tested [7,8]. The result of this has been to produce a pronounced stage shift in men presenting with prostate cancer towards localized disease in the USA, where in general the disease is treated more aggressively. It could certainly be argued that this is the reason for the markedly different reductions in prostate cancer death rates on the two sides of the Atlantic.

AS is a still experimental option for men with ‘indolent’ prostate cancer; moreover, there is no reliable method at present to identify this disease with certainty. Low-risk prostate cancer is not necessarily ‘indolent’ disease, particularly in younger men with a long life-expectancy. Currently, there is no good evidence to inform us what the best treatment is for low-risk prostate cancer, and while we can identify disease which has already progressed, we have unreliable methods to determine which patients are progressing within the ‘window of curability’ and who will benefit from treatment. Patients need to be informed about both AS and active intervention, and their respective risks and benefits equally. The NICE panel has failed to highlight the fact that there is currently little or no evidence in this area to suggest best practice. Ongoing trials are addressing the uncertainties and controversies, and it is therefore premature to make strong recommendations about ‘how best’ to manage prostate cancer without highlighting these uncertainties. There is a risk that promoting AS as a management strategy with no firm evidence that it is safe and effective might serve only to increase the already four-fold divergence in death rates from prostate cancer in the UK as compared with the USA.

CONFLICT OF INTEREST

None declared.

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