Active surveillance of early prostate cancer

Up to 80% of men with PSA screen detected prostate cancer are overdiagnosed, that is, their cancer would never have caused any symptoms [1] .   Overdiagnosis would not matter if treatment had no adverse effects.   It would be acceptable to treat all cases, including those destined never to cause symptoms, if treatment was problem-free.   However, while radical treatment for prostate cancer may or may not improve a man’s longevity, it can certainly have a big impact on his lifestyle.    Ideally, such intervention should be restricted to those who need it.   Active surveillance aims to individualise the management of early prostate cancer by selecting only those men with significant cancers for curative treatment [2] .  

Patients on active surveillance are closely monitored using serum PSA levels and repeat prostate biopsies.   The choice between curative treatment and continued observation is based on evidence of disease progression during this monitoring.   Active surveillance must be distinguished from watchful waiting, which for decades has described a policy of observation with the use of palliative treatment for symptomatic progression.   Put another way in order to emphasise the differences between these two contrasting approaches, whereas watchful waiting involves relatively lax observation with late, palliative treatment for those who develop symptoms of progressive disease, active surveillance involves close monitoring with early, curative treatment in those with evidence of biochemical or histological progression.

The concept of active surveillance was formally described for the first time in 2001 by Richard Choo from Toronto, in a report of ‘watchful observation with selective delayed intervention for clinical, histologic, or PSA progression’ [3] .   Eligibility was restricted to men with clinical stage T1b-T2b disease with a Gleason Score < 7, and initial PSA < 15 ng/ml.   Men were followed every 3 months for the first 2 years and then six-monthly, with digital rectal examination and PSA testing on each visit. Repeat biopsy was performed at 18 months.   Indications for radical treatment were PSA progression, defined as a PSA doubling time < 2 years; histologic progression, defined as upgrading to Gleason score > 8 on re-biopsy; or clinical progression.   The latest update of this study included data on 206 men, with a median initial PSA of 6.5 ng/ml [4] .   At a median follow-up of 29 months, 48 had received curative treatment, 4 had died of unrelated causes, and 154 men remained on observation.

Our own initial experience is similarly encouraging.     Between 1993 and 2001, 80 men with early prostate cancer were managed using active surveillance at the Marsden. To date, ten have received curative treatment, three have died from unrelated causes, and 67 continue on observation. No patient has developed metastatic disease, and none has died of prostate cancer.    It is interesting to note that the median PSA doubling time in the Marsden series is as long as 12 years, suggesting an indolent course of disease in most cases.  

In the light of these encouraging initial results, a prospective clinical trial of active surveillance was started at the Royal Marsden Hospital in 2002.   To date, over 200 men with early prostate cancer have been recruited.   Men in the trial are closely monitored with monthly PSA levels for the first 12 months, MRI scans of the prostate, and repeat prostate biopsies.   Preliminary results suggest that approximately 80% of men in the trial will avoid the need for curative treatment of their prostate cancer.

Active surveillance is not just an attractive alternative to immediate treatment, but also an opportunity for clinical and translational research [5] .   Active surveillance can provide a unique insight into the natural history of prostate cancer, and so will make it possible to identify new markers of prostate cancer behaviour.   Men on active surveillance at the Royal Marsden are invited to give samples of blood and urine for this type of research.   The PROACTIV trial, which is under development, will aim to study the effect of nutritional interventions on the rate of prostate cancer progression in men with early prostate cancer managed by active surveillance.   It is hoped that this ‘tertiary prevention’ approach using well-tolerated nutritional supplements might avoid the need for conventional curative treatments in some patients.

In summary, active surveillance is an attractive approach to the management of early prostate cancer, which may spare men the side effects of treatment, without compromising survival. Active surveillance also provides an ideal setting for research to identify new markers, which, in the future, could improve our ability to determine which men need, and which men do not need, treatment for their prostate cancer.  

Men with early prostate cancer (PSA less than 15, Gleason score less than or equal to 7) aged less than 80 years who would like to find out more about the active surveillance research program at the Institute of Cancer Research and the Royal Marsden Hospital should contact Dr. Chris Parker

(Chris.Parker@rmh.nhs.uk ).

References

1.                Yao, S.L. and G. Lu-Yao, Understanding and appreciating overdiagnosis in the PSA era. J Natl Cancer Inst, 2002. 94 (13): p. 958-60.

2.                Parker, C., Active surveillance: an individualized approach to early prostate cancer. BJU Int, 2003. 92 (1): p. 2-3.

3.                Choo, R., et al., PSA Doubling time of prostate carcinoma managed with watchful observation alone. Int. J. Radiat. Oncol. Biol. Phys., 2001. 50 (3): p. 615-620.

4.                Choo, R., 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 (4): p. 1664-9.

5.                Parker, C., Active surveillance: towards a new paradigm in the management of early prostate cancer. Lancet Oncol, 2004. 5 (2): p. 101-6.