Dual therapy best for nasty prostate cancer

Combination therapy that adds radiation to a standard medication for localized but aggressive prostate cancer results in longer survival and fewer signs of relapse than treatment with the drugs alone, Scandinavian scientists report online December 16 in The Lancet.

There hasn’t been a clear consensus on how best to treat such malignancies, which comprise roughly 10 to 20 percent of prostate cancer cases. Doctors call these growths locally advanced prostate cancers — tumors that are marked by fast growth and can even be felt by a doctor during a routine prostate examination. And although the cancer hasn’t spread to lymph nodes or organs beyond the prostate, it has often expanded to the outside of the gland and can be lethal.

For such patients, doctors can use radiation treatments to kill cancer cells, or prescribe drug therapy to suppress the testosterone that fuels prostate cancer growth. The benefits of using both hadn’t been ascertained until now.

“These are exciting results,” says radiation oncologist Colleen Lawton of the Medical College of Wisconsin, in Milwaukee. “This confirms what we’ve all been thinking. It’s pretty clear that dual therapy should be used” for such patients, she says.

Researchers at 47 medical centers in Sweden, Denmark and Norway enrolled 875 men with this form of prostate cancer, average age 66, into a trial lasting from 1996 to 2002. Half were randomly assigned to get drugs only, while the others also received radiation treatments, says study coauthor Anders Widmark, a medical and radiation oncologist at Umeå University in Sweden.

After an average follow-up of 7 ½ years, 79 men in the drugs-only group had died of prostate cancer or related causes, compared with 37 in the group that received radiation and drugs. Deaths from other causes were roughly equal between the groups.

What’s more, 285 men assigned to the drugs-only group — but only 77 men getting the combined therapies — experienced warning signs of a return of their prostate cancer as evidenced by an increase in their prostate specific antigen (PSA) score. This measurement, obtained by a blood test, is a proxy for cancer and a jump in the score reveals “a very early relapse stage,” says Widmark.

“[This] is a pivotal trial, and is the first to show an overall survival advantage for radiotherapy in the primary treatment of prostate cancer,” according to Alex Tan of the Noe Valley Clinic in San Francisco and Chris Parker of the Institute of Cancer Research in Sutton, U.K., writing in the same issue of The Lancet. “The results should change current practice, making long-term hormonal therapy plus radical radiotherapy the standard of care for men with locally advanced prostate cancer.”

Lawton agrees. “This says that radiation is playing a very significant role in local control” of the cancer, she says. “It’s pretty clear that dual therapy should be used.”

Whether dual therapy would help prostate cancer patients who have slower-growing malignancies, the vast majority, remains unclear, these researchers say. A course called “watchful waiting” may be best for elderly, frail men in that situation, Lawton says, whereas young or middle-aged men with slow-growing cancer have other options such as surgery or implantation of highly localized radioactive capsules.

In the new study, some well-known side effects of prostate cancer treatment showed up, and men getting the combined treatment experienced more of them than those on drugs alone. For example, five years into the follow-up period, roughly twice as many men in the combined therapy group than in the drugs-only group —7 percent versus 3 percent — reported urinary incontinence. And roughly 9 in 10 men receiving the dual therapy reported erectile problems, compared with 8 in 10 men getting drugs alone.

On a more positive note, Widmark says radiation therapy has advanced since these men were treated and can now deliver more specifically targeted doses that are 10 percent greater than those used in much of this trial. Research has shown an added clinical benefit from the higher doses, he says.

“Indeed, it is possible that the trial could underestimate the true benefit of radiotherapy,” Tan and Parker note.