According to a recent study’s findings, most men with prostate cancer that is small and restricted to the prostate gland, yet is at risk of growing and spreading, get better if they are treated with radiotherapy, in accordance with androgen deprivation therapy, which lowers their levels of the male hormone, testosterone.
The study’s findings, which were presented at the 33rd conference of the European Society for Radiotherapy and Oncology (ESTRO33) in Vienna, are expected to change medical practice and treatment options for prostate cancer.
"Although we need longer follow-up to assess the impact on these men's overall survival, these findings need to be taken into account in daily clinical practice. They show that three-dimensional conformal radiotherapy, whether intensity modulated or not, and regardless of the dose level, has to be combined with short-term androgen deprivation therapy in order to obtain a significant decrease in the risk of relapse. Therefore, during multidisciplinary team meetings to discuss a patient's treatment, this combined treatment approach should be one of the options proposed for men with localized prostate cancer that has an intermediate or high risk of growing and spreading,” said professor of radiation oncology at Grenoble University Hospital, Grenoble, France, Michel Bolla.
Bolla and his team from 37 centers in 14 countries recruited 819 men to a clinical trial. The patients had early stage prostate tumors, as verified by analyses of biopsy samples and levels of prostate specific antigen (PSA), that were in-between or high risk of metastasizing to other parts of the body.
Patients were randomized to undergo either radiotherapy alone or radiotherapy and two injections under the skin of hormone drugs called luteinizing hormone-releasing hormone analogues (LH-RH analogues), which lower levels of testosterone to cause reversible chemical castration. Each drug injection lasted three months; the first was administered on the first day of irradiation and the second three months later. When LH-RH analogues are first administered, testosterone levels go up temporarily before falling to very low levels. This effect is called flare and, in order to prevent it, the patients received an oral anti-androgen (bicalutamide, 50 mg per day) for 15 days prior to the first injection.
Physicians could select between one of three irradiation doses, 70, 74 or 78 Grays (Gy). They followed up the men for a mean of 7.2 years and discovered that, regardless of the radiotherapy dose and whether it was intensity modulated or not, the 403 men who had been treated with radiotherapy in conjunction with hormone treatment were considerably less likely to have suffered a relapse and progression of their cancer than the 407 men who had been treated with radiotherapy alone; whereas nine men did not receive the planned treatment.
Men undergoing the joint treatment had nearly half the risk (47%) of biochemical progression of their disease as opposed to men treated with radiotherapy alone. In the combined treatment group, 118 men had a biochemical progression of their disease as opposed to 201 men in the radiotherapy only group; biochemical progression was evaluated according to whether or not PSA values had risen above the lowest level plus two nanograms per milli-litre; if it had risen, then this required confirmation in subsequent checks.
Five years following treatment, the men in the joint treatment group were doing considerably better.
"They had better survival without biochemical progression. Among those receiving the combined treatment, 17.5% had progressed compared to 30.7% receiving radiotherapy alone,” said Bolla.
When the researchers examined clinical progression of the disease, whether the cancer had recurred, spread to other parts of the body (proven by biopsies and imaging) or the patients had died, they discovered that five years following their treatment 88.7% of the men in the combined treatment group had not progressed, as opposed to 80.8% of men undergoing radiotherapy only.
Over the course of the study, 152 patients have died, of which 25 died from prostate cancer. Side-effects, relating mainly to problems with urination, were accounted for in 5.9% of patients receiving the combined treatment compared to 3.6% of patients on radiotherapy alone. Problems with sexual function were higher in the combined treatment group: 27% versus 19.4%.
"These results show that, in men with localized prostate cancer that is at risk of recurring and spreading, the addition of six months of hormonal treatment to radiotherapy improves the time these men survive without their disease progressing. It is important to ensure that the radiation treatment is of the best quality; further clinical research is required to optimize radiation techniques and to find new hormonal treatments,” concluded Bolla.