Effect of a short course of neoadjuvant hormonal therapy on the response to subsequent androgen suppression in prostate cancer patients with relapse after radiotherapy: a secondary analysis of the randomized protocol RTOG 86-10.
OBJECTIVE
To compare, by a secondary analysis, the therapeutic benefits of androgen suppression in protocol prostate cancer patients with relapse after radiotherapy (RT) for locally advanced disease who, in the Phase III trial beginning in 1987, were assigned to receive or not receive a short course of neoadjuvant maximal androgen suppression before definitive RT.


METHODS
Between 1987 and 1991, 456 patients were entered in the Radiation Therapy Oncology Group trail 86-10 and randomized to receive (Arm I) or not to receive (Arm II) neoadjuvant hormonal therapy (HT), which was 4 months of goserelin (3.6 mg every 4 weeks) and flutamide (250 mg t.i.d.) before and during RT for bulky T2-T4 tumors. The overall and disease-specific survival after both randomization and salvage HT for patients with relapse was evaluated, as well as the duration of response in those patients undergoing salvage HT. The outcomes in patients who had received neoadjuvant HT vs. those who had not were compared. The median follow-up after randomization for all alive patients was 9.0 years and was 5.5 years for alive patients after beginning salvage HT.


RESULTS
Fewer patients received salvage HT on Arm I than on Arm II (45% vs. 63%, p <0.001). The outcomes by randomized treatment arm (I vs. II) from the time of beginning salvage HT were similar. At 5 years after salvage HT, the overall survival rates were 41% and 41% and the disease-specific survival rates were 50% and 50%. At 8 years after randomization, the overall survival rates were 47% and 44% and the disease-specific survival rates were 55% and 56%.


CONCLUSIONS
Although a 4-month course of neoadjuvant and concurrent maximum androgen suppression and RT (compared with RT alone) significantly increases the freedom from relapse rate and freedom from receiving salvage HT, it does not compromise the long-term beneficial effect of subsequent salvage HT, if needed for relapse. These findings with long follow-up in patients treated for locally advanced disease diagnosed 9-14 years previously should help allay concerns of the possible development of "resistance" to androgen suppression when 4-month courses of neoadjuvant HT are used before primary treatment.
Shipley
William U
WU
Massachusetts General Hospital, Boston, MA 02114, USA. wshipley@partners.org
Lu
J D
JD
Pilepich
Michael V
MV
Heydon
Kateri
K
Roach
Mack
M
Wolkov
Harvey B
HB
Sause
William T
WT
Rubin
Philip
P
Lawton
Colleen A
CA
Machtay
Mitchell
M
D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005485:Flutamide / Q000627:therapeutic use; D017273:Goserelin / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy*; D012008:Recurrence; D016879:Salvage Therapy; D013997:Time Factors; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D017273:Goserelin; D005485:Flutamide