Introduction

Prostate cancer is the second-leading cause of cancer deaths in men in the USA. The optimal treatment for early stage disease remains controversial. A new study from Scandinavia has stirred the debate. The findings show that radical prostatectomy, compared with 'watchful waiting', is associated with an approximately 50% reduction in cancer-specific mortality at 8 years after surgery, and a similar reduction in the frequency of distant metastases. The study reports, together with an accompanying editorial¹, are the basis of this summary.

The Scandinavian Study

Over a ten-year period, 695 Swedish men aged 60 to 70 with early prostate cancer were enrolled. Adenocarcinoma was verified by cytology or histology. Tumors were classified by the International Union against Cancer (IUC) stages as T1b, T1c, or T2. Histology of biopsy material had to show less than 25% as Gleason grade 4, and less than 5% as Gleason grade 5. Patients were randomized to a watchful-waiting group or a radical prostatectomy group, with stratification according to degree of differentiation and study center. The watchful-waiting group patients received no immediate treatment, but transurethral resection was recommended for local progression.

The median follow-up period was 6.2 years. During follow-up, 16 of the 347 (4.6%) radical prostatectomy men died of prostate cancer, compared with 31 of the 348 (8.9%) men who were allocated to watchful waiting. The relative hazard was 0.5 (95% CI, 0.27-0.91). In those who had surgery, 35 men (10.1%) had distant metastases, compared with 54 (15.5%) in the watchful-waiting group; the relative hazard was 0.63 (95% CI, 0.41-0.96).

The overall death rate from all causes was not significantly different in the two groups. A total of 53 men (15.3%) who had prostatectomy died, compared to 62 men (17.8%) in the watchful-waiting group. The study was probably insufficiently powered to demonstrate a significant difference in this respect.

Adverse events during 4 years of follow-up

Men in the study were assessed for 'quality of life' symptoms and signs involving sexual, urinary, and bowel function, as well as psychological factors, during the first 4 years of follow-up. Information was obtained from 326 men (166 from the radical prostatectomy and 187 from the watchful-waiting groups), using a mailed questionnaire.

Regarding sexual function, 45% in the watchful-waiting group experienced erectile dysfunction, compared with 80% in the prostatectomy group; the relative risk after prostatectomy was 1.8 (95% CI, 1.5-2.2). Distress from compromised sexual function was reported as moderate or great in 40% of the watchful-waiting men, and in 56% of the prostatectomy men; the relative risk after prostatectomy for distress was 1.4 (95%CI, 1.1-1.8).

Urinary leakage was more common after prostatectomy than with watchful waiting - 49% vs. 21% (relative risk 2.3; 95%CI, 1.6-3.2). On the other hand, symptoms of urinary obstruction were more frequent in the watchful-waiting men; a weak stream was reported by 44% of them, compared with 28% in the post-prostatectomy group (relative risk after prostatectomy 0.6; 95%CI, 0.5-0.9).

Bowel function, anxiety, depression, well-being, and subjective quality of life were similar in the two study groups.

Relevance of the study findings

The findings in this rigorous study provide clear evidence that surgical treatment of localized prostate cancer reduces the risk of death and the distant spread of the cancer. The actual benefit may appear small; to prevent one death from prostate cancer over an 8-year period, 17 men would have to have surgery.

However, the degree of benefit cannot be generalized to the US population, as the diagnosis was made clinically. Typically, the tumors had grown enough to cause symptoms (e.g. dysuria) and 75% of the patients had palpable disease; only 10% were diagnosed because of a raised prostate-specific antigen (PSA) level. Such a population is not representative of the US situation, where 75% of men diagnosed as having prostate cancer are detected by biopsy because of an elevated PSA level. It's known that PSA screening finds tumors 5 to 7 years before they would cause symptoms. Consequently, the Swedish patients were probably considerably older than their US counterparts. Earlier diagnosis (with the help of PSA screening) followed by radical prostatectomy treatment may well widen the advantage of surgery found here over watchful waiting. Large-scale studies along these lines are now running in the USA and Europe.

It's possible, also, that the frequency of erectile dysfunction may be considerably higher in the Swedish men who had prostatectomies than in men in the USA treated by surgery. Nerve-sparing surgery was not routinely done in the Scandinavian study. In US series, potency rates of 62% to 86% are commonly reported.

It's important to remember that other treatments for prostate cancer - e.g. external beam radiation, radioactive seed implants - have not yet been evaluated in a similar rigorous fashion as that used in this study.

Consequences

While the findings of the Swedish study appear conclusive, they should not lead to the practice that all prostate cancers require radical prostatectomy. Many patients are best treated by watchful waiting - those that are too old or too ill to survive longer than 10 years. Further, some men with a slight increase in their PSA but no palpable tumor -- about 10% to 20% -- are candidates for watchful waiting. And for those with larger tumors, radiotherapy may be the most appropriate treatment.

Randomized and cohort studies that compare radical prostatectomy with radiotherapy are being developed. Until results of these, and other, studies are available, physicians should fully inform men with prostate cancer about their treatment options, and help them find the best specialist for the treatment they choose.