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Key Words

Prostate cancer, prostatectomy, radiotherapy, watchful waiting. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary ³.)

Summary

Men with locally advanced prostate cancer who underwent surgery to remove their prostate gland followed by radiotherapy were less likely to have their cancer return and spread than men who did not receive the additional radiotherapy.

Source

The Lancet, August 13, 2005 (see the journal abstract).

Background

Patients with advanced prostate cancer often undergo surgery to remove the diseased cells. Primary surgery to remove the prostate gland and related lymph nodes is called radical prostatectomy. This surgery is almost always curative when all of the cancer cells are confined within the prostate. However, for men with locally advanced, stage III cancer (cancer that has spread to the tissues beyond the prostate gland but not to other organs), the likelihood of the cancer returning (recurrence) after surgery tends to be high.

Radiotherapy (in which high-energy beams such as x-rays are used to shrink or kill cancer cells) is sometimes used instead of surgery to treat men with early stage prostate cancer. Researchers with the study described here wondered whether radiotherapy given immediately after surgery might help men with advanced prostate cancer do better than just surgery alone.

The prostate-specific antigen (PSA) test is a useful procedure to monitor recurrence. Most men have very low levels of PSA in their blood; prostate cancer causes these levels to rise.

The Study

In this European, multicenter phase III study (called EORTC 22911), researchers enrolled 1,005 men with locally advanced prostate cancer who had had a radical prostatectomy and were considered at high risk for having the disease return and spread. The men were randomly assigned to one of two groups. Half of them (502) received adjuvant (additional) radiation treatments over a six-week period starting within four months of their surgery, and the other half (503) were monitored through watchful waiting. PSA levels were taken at regular intervals to detect increased antigen levels.

The study’s lead author is Michel Bolla, M.D., Universitaire A. Michallon, Grenoble, France.

Results

After a median follow-up period of five years, 74 percent of men receiving radiation therapy after radical prostatectomy were cancer-free, based on their PSA levels, compared with 53 percent of the watchful-waiting group; these results were statistically significant. Clinical progression-free survival (survival without any symptoms) also was significantly improved in the radiotherapy group.

However, no significant difference was noted between the radiotherapy and watchful-waiting groups in terms of overall survival during the five-year follow-up period. Side effects were more frequent in the radiation group, and included severe diarrhea and greatly increased urinary frequency.

Comments

The results from this large clinical trial are “likely to change patterns of care in locally advanced prostate cancer,” wrote Stefan Höcht, M.D., and Wolfgang Hinkelbein, M.D. of Charité Universitätsmedizin in Berlin, Germany, in an accompanying commentary.

Limitations

This study examines the use of radiotherapy immediately after radical prostatectomy in men at high risk for recurrence. Currently, there are differences of opinion about whether this should be the standard of care or whether doctors should wait to see if PSA levels rise and only start radiotherapy at that time.

An advantage to the second approach (sometimes referred to as “early salvage treatment”) is that it allows some patients to avoid additional treatment (and its side effects) that they might not need anyway. According to Anurag Singh, M.D., a radiation oncologist with the National Cancer Institute’s Center for Cancer Research, studies of men at risk of prostate cancer recurrence estimate that for close to 50 percent of these patients, additional radiotherapy is not needed because the disease will not come back.

“This study proves the utility of postoperative radiotherapy in high-risk patients after radical prostatectomy,” said Singh. “It does not, however, address the question of the day; that is, is there any detriment to closely monitoring PSA levels and treating only if there is a rise in the PSA?” More studies are needed, he added, to determine which patients would likely benefit from the early salvage approach.

Höcht and Hinkelbein agree: “Salvage therapy is quite effective in the case of [PSA] relapse after prostatectomy,” they noted in their commentary. “The question still to be answered is whether adjuvant irradiation is superior to early salvage treatment as soon as [PSA] rises.”

Glossary Terms

Any substance that causes the body to make a specific immune response.

Cancer that has spread from where it started to nearby tissue or lymph nodes.

A statistics term. The middle value in a set of measurements.

A study to compare the results of people taking a new treatment with the results of people taking the standard treatment (for example, which group has better survival rates or fewer side effects). In most cases, studies move into phase III only after a treatment seems to work in phases I and II. Phase III trials may include hundreds of people.

After surgery.

An operation to remove part or all of the prostate. Radical (or total) prostatectomy is the removal of the entire prostate and some of the tissue around it.

The use of high-energy radiation from x-rays, gamma rays, neutrons, protons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body near cancer cells (internal radiation therapy). Systemic radiotherapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that travels in the blood to tissues throughout the body. Also called irradiation and radiation therapy.

In medicine, treatment that experts agree is appropriate, accepted, and widely used. Health care providers are obligated to provide patients with the standard of care. Also called best practice and standard therapy.

Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. Also called significant.

Having to do with urine or the organs of the body that produce and get rid of urine.

Closely monitoring a patient's condition but withholding treatment until symptoms appear or change. Also called active surveillance, expectant management, and observation.