Primary Androgen Deprivation Therapy for Nonmetastatic Prostate Cancer in Asia: Unique or Not?
Authors: Masaki Shiota
Journal: Journal of the National Comprehensive Cancer Network (2019)

ince the work of Huggins and Hodges in the mid 1900s, primary androgen deprivation therapy (PADT) has been the backbone therapy for metastatic prostate cancer.It has recently been combined with upfront docetaxel or abiraterone.Although PADT initially demonstrates excellent antitumor effects and palliates symptoms in most patients, castration-resistant disease often develops.Thus, PADT is recognized as being palliative rather than curative.Although the survival benefit of PADT is vague, this treatment modality has been commonly used in clinical practice for nonmetastatic disease, especially in the elderly.However, 2 large cohort studies using a nationwide US database recently suggested that PADT has no long-term survival benefits in elderly men with localized prostate cancer. 1,2ubsequently, in the randomized EORTC 30891 trial, PADT showed a comparable outcome to observation (deferred ADT) in most cases of nonmetastatic disease, but not in very aggressive disease with a 3-to 5-year prognosis. 3Meanwhile, in the randomized SPCG-4 trial in Europe, therapy with radical prostatectomy (RP) showed a superior outcome to observation. 4Furthermore, the addition of radiotherapy to PADT for locally advanced disease was shown to improve survival compared with PADT alone in the randomized PR3/ PR07 trial. 5Accordingly, it was suggested that radical therapies are likely to show superior survival to PADT or observation alone.Consequently, based on data obtained in Western countries, most guidelines, including the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer, recommend active surveillance, radical therapy, or observation for nonmetastatic prostate cancer based on disease status and patient life expectancy.However, these guidelines recommend PADT as an option only for locally advanced disease if life expectancy is #5 years and the patient is asymptomatic. 6ompared with white and black patients, PADT was suggested to be more effective in Asian populations. 7Furthermore, adverse effects associated with ADT, such as decreases in bone mineral density and possible increased risk of cardiovascular disease, are suggested to be milder in Asian versus Western populations. 8It was reported that the survival of patients with nonmetastatic prostate cancer was comparable to the life expectancy of the general population, 9 although careful interpretation is required; men undergoing prostate biopsy, even for localized prostate cancer, are so-called healthy, whereas the general population includes very sick men.As a result, noninferior survival with PADT compared with radical therapy can be hypothesized as possible in Asian populations.Accordingly, in addition to the recommendation of PADT in the NCCN Guidelines, the NCCN Guidelines-Asia Consensus Statement for Prostate Cancer 8 state that PADT may be considered as a possible treatment option for the following select patients: (1) low-and intermediate-risk patients with life expectancy $10 years if they are unable to commit to radical therapy or active surveillance; (2) low-and intermediate-risk patients with life expectancy ,10 years; and (3) high-risk patients, in whom ADT is suggested as a therapeutic option for those who are unfit or inaccessible for radical therapy, or have a short life expectancy.However, is it true that PADT is an alternative therapy for radical therapy such as RP for nonmetastatic prostate cancer in Asian populations?In their article in this issue, Ha et al 10 reported differential overall survival between RP and PADT using a health See page 441 for related article.