Platinum Priority – Prostate CancerEditorial by Bruce J. Trock on pp. 251–252 of this issueAdjuvant Radiotherapy Versus Wait-and-See After Radical Prostatectomy: 10-year Follow-up of the ARO 96–02/AUO AP 09/95 Trial
Introduction
For patients with localized prostate cancer (PCa), radical prostatectomy (RP) and external-beam radiotherapy (RT) enable an adjusted 10-yr overall survival (OS) of 83% and 89%, respectively [1]. After prostatectomy, 15–25% of the patients experience recurrence [2]. With adverse risk factors such as high serum levels of prostate-specific antigen (PSA), pT3, positive surgical margins (R1), and Gleason score ≥8, the 10-yr biochemical recurrence rates may grow to 75% [3]. Although not all PSA-relapsing patients will develop clinical progression, surgery alone may be inadequate for specific subgroups [4].
Three randomized prospective trials—SWOG 8794, European Organization for Research and Treatment of Cancer (EORTC) 22911 (10-yr data), and ARO 96–02 (5-yr data)—reported improved (biochemical) progression-free survival (PFS) after adjuvant RT (ART) with hazard ratios (HRs) between 0.43 and 0.53 [5], [6], [7]. Only SWOG also found a profit in OS and metastasis-free survival (MFS). As PSA recurrence precedes clinical progression by a median of 8 yr, long-term results of these studies are of major interest [8]. In this paper, we report the 10-yr follow-up of the ARO/AUO trial. Exclusively including patients who achieved an undetectable PSA after RP, the ARO/AUO trial is the one truly adjuvant trial among the three. Different from the two older trials, ARO 96–02 consistently incorporated three-dimensional (3D) conformal treatment planning, improving comparability with recent techniques.
Section snippets
Trial design and participants
Tumor stages were determined according to the 1992 International Union Against Cancer criteria [9]. Patients had histologically proven cT1–cT3N0 PCa preoperatively. Before entry, all patients underwent preoperative and postoperative PSA testing, bone scan, and chest radiography. Eligible patients had histologically proven adenocarcinoma of the prostate with no known distant metastases and a pathologic stage pT3–4 pN0 with positive or negative surgical margins. Patients had to be <76 yr, with a
Results
From 1997 to 2004, 388 patients entered the trial after RP but before achieving an undetectable PSA: 194 patients were assigned to the WS policy (arm A), and 194 patients were assigned to ART (arm B). Three patients were excluded because of immediate HT (Fig. 1). Seventy-eight patients (20%) who did not achieve an undetectable PSA were stated to have progressive disease (arm A, 33 patients; arm B, 45 patients). Of these 78 patients, 74 underwent RT; 4 patients refused RT. In this paper, we
Discussion
Concordant with earlier results and other prospectively randomized clinical trials, our data show an improved PFS after ART that reduced the relative risk of long-term biochemical relapse by 51% [5], [6], [7]. Our study differs from the SWOG and the EORTC trials in that achieving an undetectable PSA after RP (<0.5 ng/ml) was mandatory for inclusion. Thus, the ITT2 cohort demonstrates directly that PSA-negative patients do profit from ART after RP. Indirectly, this finding had also been deduced
Conclusions
We demonstrated that ART can improve biochemical PFS after RP for pT3 PCa. RT-related toxicity was rare and largely mild to moderate. Men with positive surgical margins are the most likely candidates to profit from adjuvant treatment. However, proving an effect on hard end points may require larger patient cohorts and longer follow-up.
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