A prospective phase III randomized trial of hypofractionation versus conventional fractionation in patients with high-risk prostate cancer.
OBJECTIVE
To compare the toxicity and efficacy of hypofractionated (62 Gy/20 fractions/5 weeks, 4 fractions per week) vs. conventional fractionation radiotherapy (80 Gy/40 fractions/8 weeks) in patients with high-risk prostate cancer.


METHODS
From January 2003 to December 2007, 168 patients were randomized to receive either hypofractionated or conventional fractionated schedules of three-dimensional conformal radiotherapy to the prostate and seminal vesicles. All patients received a 9-month course of total androgen deprivation (TAD), and radiotherapy started 2 months thereafter.


RESULTS
The median (range) follow-up was 32 (8-66) and 35 (7-64) months in the hypofractionation and conventional fractionation arms, respectively. No difference was found for late toxicity between the two treatment groups, with 3-year Grade 2 rates of 17% and 16% for gastrointestinal and 14% and 11% for genitourinary in the hypofractionation and conventional fractionation groups, respectively. The 3-year freedom from biochemical failure (FFBF) rates were 87% and 79% in the hypofractionation and conventional fractionation groups, respectively (p = 0.035). The 3-year FFBF rates in patients at a very high risk (i.e., pretreatment prostate-specific antigen (iPSA) >20 ng/mL, Gleason score >or=8, or T >or=2c), were 88% and 76% (p = 0.014) in the former and latter arm, respectively. The multivariate Cox analysis confirmed fractionation, iPSA, and Gleason score as significant prognostic factors.


CONCLUSIONS
Our findings suggest that late toxicity is equivalent between the two treatment groups and that the hypofractionated schedule used in this trial is superior to the conventional fractionation in terms of FFBF.
Arcangeli
Giorgio
G
Department of Radiotherapy, Regina Elena National Cancer Institute, Rome, Italy. arcangeli@ifo.it
Saracino
Biancamaria
B
Gomellini
Sara
S
Petrongari
Maria Grazia
MG
Arcangeli
Stefano
S
Sentinelli
Steno
S
Marzi
Simona
S
Landoni
Valeria
V
Fowler
Jack
J
Strigari
Lidia
L
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D000813:Anilides / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019583:Dose Fractionation, Radiation; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009570:Nitriles / Q000627:therapeutic use; D011446:Prospective Studies; D011467:Prostate / Q000528:radiation effects; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000517:prevention & control; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000379:methods*; D012669:Seminal Vesicles / Q000528:radiation effects; D014105:Tosyl Compounds / Q000627:therapeutic use
D000726:Androgen Antagonists; D000813:Anilides; D000970:Antineoplastic Agents; D009570:Nitriles; D014105:Tosyl Compounds; C053541:bicalutamide; D017430:Prostate-Specific Antigen