Early localised prostate cancer may accelerate after 15 years

Watchful waiting is not a good idea for some patients with early localised prostate cancer because local progression and aggressive metastatic disease may develop after 15 years. This finding comes from a 20 year study—one of the largest and longest yet—from a Swedish group and published in JAMA (2004;291: 2713-9)

“We had not anticipated this increased risk after 15 years,” the lead author, Dr Jan-Erik Johansson of Örebro University Hospital, told the BMJ.

The study followed 223 patients with early stage, localised prostate cancer. They received no initial treatment if the cancer was localised to the prostate as judged by digital rectal examination and there were no distant metastases. If the cancer progressed to symptomatic disease, patients were treated with oestrogens or orchidectomy. Local progression without generalised disease may cause substantial suffering, the authors wrote. About 70 patients received hormonal treatment, Dr Johansson told the BMJ.

During the first 15 years, most cancers followed an indolent course: 25 (11%) of patients died of prostate cancer. Ten more died during follow up.

Follow up from 15 years to 20 years showed a “substantial decrease in cumulative progression-free survival (from 45% to 36%), survival without metastases (from 76.9% to 51.2%), and prostate-cancer-specific survival (from 78.7% to 54.4%).” Mortality from prostate cancer increased from 15 per 1000 (95% confidence interval 10 to 21 per 1000) person years during the first 15 years to 44 per 1000 (22 to 88 per 1000) person years beyond 15 years of follow up (P=0.01).

Dr Johansson and colleagues followed the group for a mean of 21 years, beginning in 1977. About half the patients were diagnosed as a result of cancer being found during resection for supposedly benign prostatic enlargement. The mean age at diagnosis was 72 (range 41 to 91) years.

All 223 patients were followed until death or September 2001; none were lost to follow up. Patients who agreed had a new fine needle biopsy every other year during the first six years of follow up.

During the study period, 89 patients (40%) had progression of disease, with 39 of them (17% of the entire cohort) developing generalised disease; 203 patients (91%) died—35 (16%) of prostate cancer. Patients younger than 70 and those with poorly differentiated cancer were more likely to die of cancer than older patients.

The unexpected finding was that disease and death from prostate cancer accelerated after 15 years, regardless of the stage at which the tumours were first diagnosed.