Prostate UK Logo

Prostate news article, June 2008


ARE THE 'NICE' GUIDELINES PROMULGATING ACTIVE SURVEILLANCE FOR LOW-RISK PROSTATE CANCER JUSTIFIED BY AVAILABLE EVIDENCE?

 

Article by:   Professor Roger Kirby, Chairman, Prostate UK

 Roger Kirby

Very recently, guidelines for the management of localised prostate cancer have been issued by the National Institute of 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 emphasised the role of active surveillance for men with so called “low risk” prostate cancer. But can we really define with certainty the men with “indolent” cancers which have a minimal risk of progression? And can we truly recognise 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 less than 10 ng/ml, a Gleason score of 6 or less, as well as no disease being palpable on digital rectal examination1. Others have suggested protocols for active surveillance. Most include the number and percentage of cores involved by cancer and three monthly digital rectal examination and PSA determination followed by a repeat ultrasound-guided biopsy of the prostate and MRI at one 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 men managed in this way suffer psychologically(4)

A note of caution however comes from a current paper in the online version of Cancer, Dr Patricia Harnden and colleagues(5) report a meta-analysis on whether patients with microfocal CaP on biopsy have adverse pathologic findings or any significant risk of PSA recurrence after undergoing radical prostatectomy.

A total of 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 pathologic 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 randomised. 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 cutoff value of 3mm for the prostate cancer length. The occurrence rate of no cancer at all in the radical prostatectomy specimen (“disappearing cancer”), was 0.8%. The overall estimate of the risk that patients with microfocal prostate cancer would have extracapsular extension (ECE) 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 watchful waiting studies, a rising PSA was reported in 9 of 15 patients who had a microfocus of prostate cancer. Conversion to definitive therapy occurred 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 question marks about the promulgation of active surveillance as a management strategy for prostate cancer are raised by the very recent publication online of a paper entitled “prostate-cancer mortality in the USA and UK in 1975-2004: an ecological study”. In this publication the four times greater decline in prostate cancer mortality in the USA compared with the UK since 1992 is highlighted. This period coincides with a much greater uptake of PSA screening in the USA: in 2001 57% of men in America of 50 years or older reported having a PSA test within the previous 12 months(6), by contrast in the UK, only 6% of men 45-84 were tested(7). The result of this has been to produce a pronounced stage shift in men presenting with prostate cancer towards localised disease in the United States, 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 opposite sides of the Atlantic.

Active surveillance 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, we do not have 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 active surveillance 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 active surveillance as a management strategy without firm evidence that it is safe and effective may serve only to increase the already four times divergence in death rates from prostate cancer in the UK as compared with the USA.

References:

  1. Epstein JL, Chan DW, Sokoll LJ et al (1998) Nonpalpable stage T1c prostate cancer: prediction of insignificant disease using free/total prostate specific antigen levels and needle biopsy findings. J Urol 160: 2407-2411.
  2. Klotz L. (2005) Active surveillance for prostate cancer: for whom? J Clin Oncol 23: 8165 – 8169.
  3. Klotz L. (2008) Low-risk prostate cancer can and should be managed by active surveillance and selected delayed intervention. Nat Clin Pract Urol 5: 2-3.
  4. Burnett KL, Parker C, Deanaley D et al. (2007) Does active surveillance for prostate cancer carry psychological morbidity? BJU Int 100: 540-543
  5. Harnden P, Naylor B, Shelley et al. The clinical management of patients with a small volume of prostatic cancer on biopsy: what are the risks of progression? A systematic review and meta-analysis.
  6. Cancer. 2008 Mar 1;112(5):971-81.
  7. Collin S, Martin RM, Metcalfe C et al. Prostate-cancer mortality in the USA and UK in 1975-2004: an ecological study. 2008 Oncology.the lancet.com DOI;10.1016/S1470-2045(08)70104-9.
  8. Sirovitch BE, Schwarz LM, Woolsin S. Screening men for prostate and colorectal cancer in the United States: does practice reflect the evidence? JAMA 2003;289:1414-20.
  9. Melia J, Moss S, Johns L, et al. Rates of prostate-specific antigen testing in England and Wales in asymptomatic and symptomatic patients. A cross sectional study. BJU Int 2004; 94:51-56.