Intermittent androgen deprivation is as effective as continuous therapy for men with rising prostate-specific antigen (PSA) levels after primary or salvage radiotherapy, say researchers who believe the break from treatment improves quality of life.
Overall survival did not significantly differ in the 1386 men given luteinizing hormone-releasing hormone agonist plus nonsteroidal anti-androgen continuously or in 8-month cycles, at a median of 9.1 and 8.8 years, respectively. After 7 years, the estimated cumulative rates of disease-related death were 15% and 18%, respectively.
Ninety-five percent of men in the intermittent group achieved a PSA of below 4 ng/mL after 8 months of treatment and entered the first nontreatment period, which lasted for a median of 20.1 months. Second and third nontreatment periods were achieved by 58% and 32% of patients, lasting for 13.2 and 9.1 months, respectively. Up to nine nontreatment periods were reported.
Thus, men given continuous treatment had a median treatment duration of 43.9 months compared with just 15.4 months in the intermittent treatment group. During the median 37.6 months while off treatment, intermittent patients' PSA levels were measured every 2 months until a level of 10 ng/mL was reached or there was evidence of disease progression.
Pretreatment levels of testosterone were achieved by 35% of intermittently treated patients, with 79% reaching 5 nmol/L, say Juanita Crook (British Columbia Cancer Agency, Kelowna, Canada) and co-authors.
Furthermore, intermittent treatment was associated with significantly better quality of life than continuous treatment with regard to symptoms, including hot flashes, sexual activity, and urinary symptoms. There was also a trend toward improved fatigue with intermittent treatment, as well as physical, role, and global health function domains.
"Although the cost savings from the reduction in drug use in the intermittent-therapy group (approximately one-third of that in the continuous-therapy group) may be partially offset by the closer follow-up required, this follow-up may have undefined health benefits," the team reports in The New England Journal of Medicine.
In an accompanying commentary, however, Oliver Sartor (Tulane University School of Medicine, New Orleans, USA) emphasizes that it is still unclear which asymptomatic prostate cancer patients can expect clinical consequences from rising PSA levels or will benefit from androgen deprivation.
Sartor continues: "Does early androgen-deprivation therapy in asymptomatic men with rising PSA levels provide more benefit than treatment in symptomatic men with metastases? This question bedevils our field, and we are no closer to an answer now than we were before."
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