Active surveillance versus watchful waiting for prostate cancer: UK study early results

April 27, 2005 -- UK medical researchers at the Institute of Cancer Research (UK) and Royal Marsden NHS Foundation Trust say that early results from a study they conducted suggest that many men with prostate cancer can safely avoid the need for treatment.

In the study, 80 men with early prostate cancers detected by prostate specific antigen (PSA) test and confirmed by biopsy were monitored with active surveillance, a revamped version of the old watchful waiting.

Active surveillance is described as "a new strategy aiming to individualize the management of early prostate cancer by selecting only those men with significant cancers for curative therapy." The present study was designed to demonstrate active surveillance in contrast with a policy of watchful waiting (WW).

The 80 men were diagnosed with prostate cancer between 1993 and 2002. During most of this period, prostate cancer survival rates were abysmal for men in the UK, where 30,000 cases are diagnosed each year and the disease kills 10,000 men a year. This is a much higher death rate from this cancer than in the USA and some parts of Europe.

In 1999, only 53 percent of men in England and Scotland and 48 percent in Wales were alive 5 years after diagnosis with prostate cancer compared with 83 percent in Austria, 75 percent in France and 76 percent in Iceland (See Grassroots, Man with the Hesitant Stream -- UK Prostate Cancer Survival Rates in the Toilet)

Eligibility for this UK active surveillance study included biopsy confirmed prostatic adenocarcinoma, fitness for radical treatment, clinical stage T1/T2, no nodal or metastatic cancer, PSA at or below 20 ng/mL and a Gleason score at or below 7.

PSA was measured and a digital rectal examination conducted at 3-6 month intervals. The decision between continued monitoring or radical treatment was informed by the rate of rise of PSA, and was made according to the judgment of each patient and clinician.

At a median follow-up of 42 months, 64 (80%) of the 80 patients on AS remained under observation, 11 (14%) received radical treatment and five (6%) died from other causes. No patient developed evidence of metastatic disease, none started palliative hormone therapy, and there were no deaths from prostate cancer. Of the 11 patients who received radical treatment all remained biochemically controlled with no clinical evidence of recurrent disease. The median PSA doubling time while on AS was 12 years.

Only 14 per cent of patients who took part in the study of "active surveillance" received any treatment for their cancer, which means that the remainder have avoided the risks of treatment side-effects, such as impotence and incontinence.

For contrast, a control group of 32 patients with similar disease characteristics were treated with traditional "watchful waiting" methods. These 32 men with localized prostate cancer (any T stage, N0/X, M0/X, any PSA, Gleason score </= 7) were observed until they developed symptomatic disease progression, then put on hormonal treatment. In this group, twenty (62%) of the 32 patients on WW remained on observation, eight (25%) received palliative hormonal therapy and four (12%) died, including one from prostate cancer.

By the age of 65 about half of all men will have some cancer cells in the prostate, but most will live out their natural span without the disease ever causing them any ill effects. However it is not possible to accurately predict cancer behavior in an individual, so until now treatment has been typically offered to all men diagnosed with prostate cancer.

Active surveillance aims to target treatment only to those men who need it. Patients are closely monitored using serum PSA levels with or without repeat prostate biopsies. The choice between radical treatment and observation is based on evidence of disease progression defined in terms of the PSA doubling time (PSADT) or "upgrading" at repeat biopsy.

Compared with a policy of immediate treatment in all cases, it is hoped that "active surveillance" will reduce the burden of treatment side effects without compromising survival.

The investigators say there is a marked contrast between "active surveillance" (with radical treatment for biochemical progression, e.g. rapid rise in PSA) and watchful waiting (with hormonal or other palliative treatment for symptomatic progression, e.g. urinary retention, kidney failure, bone metastatis, pain).

A prospective study is now ongoing at The Royal Marsden NHS Foundation Trust, with the support of the National Cancer Research Institute, which aims to optimize the active surveillance protocol.