Prostate CancerCombination of Adjuvant Hormonal and Radiation Therapy Significantly Prolongs Survival of Patients With pT2–4 pN+ Prostate Cancer: Results of a Matched Analysis
Introduction
Radical prostatectomy (RP) is an effective treatment for patients with organ-confined prostate cancer (PCa) [1]. Large clinical series have demonstrated that RP also represents a valid treatment modality for patients with locally advanced disease [2], [3], [4], [5], [6], [7]. According to the European Association of Urology guidelines, RP is indicated in selected patients with low-volume, high-risk localised PCa (cT3a or Gleason score 8–10 or prostate-specific antigen [PSA] >20) [1].
Although in the PSA era the diagnosis of PCa has shifted to early clinical stages, nodal metastases are indeed still diagnosed in a wide range of patients [8], [9], [10], [11], [12]. Several studies reported excellent cancer-specific outcomes of patients with histologically proven nodal metastases submitted to RP [13], [14], [15], [16], [17], [18], especially in the presence of a low volume of nodal burden [18], [19]. Oncologic outcomes of surgically treated node-positive patients has improved by early administration of adjuvant hormonal therapy (HT) [20]. Nevertheless, the effect of adjuvant radiation therapy (RT) in node-positive PCa has never been prospectively assessed. Indeed, none of the most recent large prospective randomised studies supporting the role of adjuvant RT in preventing disease recurrence and death in locally advanced PCa included patients with concomitant nodal metastases [21], [22], [23]. The idea of testing adjuvant RT in the presence of lymph node invasion (LNI) came from the evidence that node-positive PCa is not always a systemic and noncurable disease [13], [14], [15], [16], [17], [18], [19]. Administration of adjuvant RT would aim at optimising local control, thus preventing distant metastases and death [21], [22], [23], [24]. A recent retrospective study reported a significant positive impact of RT in combination with HT in patients with PCa and nodal metastases treated with RP and extended pelvic lymph node dissection (PLND) [25]. However, this study was limited by a potential patient selection bias mainly due to its retrospective and unmatched design. In fact, patients treated with adjuvant RT were those affected by more aggressive disease. For this reason, no effect of adjuvant RT on cancer-specific survival (CSS) was demonstrated on univariate survival analyses. Whether adjuvant RT was effective in preventing progression and recurrence according to the extent of nodal invasion was not tested in that study. This is key, since the number of positive nodes represents a strong predictor of survival of patients with LNI [13], [14], [15], [16], [17], [18], [19]. To solve these issues, we assessed the effect of adjuvant RT in node-positive PCa including two homogeneous matched patient cohorts exposed to either adjuvant RT plus HT or adjuvant HT alone after surgery.
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Materials and methods
We analysed data on 703 consecutive pT2–4 pN+ M0 patients treated with RP, PLND, and adjuvant treatments at two large academic institutions between September 1988 and January 2003. All patients were preoperatively staged with abdominal computed tomography (CT) and bone scan to exclude the presence of visceral and bone metastases, respectively.
Of these patients, 171 (24.3%) received a combination of adjuvant HT and RT, and 532 (75.7%) received adjuvant HT alone. The decision to administer one or
Results
The study cohort characteristics are stratified according to the type of adjuvant treatment administered (namely adjuvant RT plus HT vs HT alone) as well as to analysis type (unmatched vs matched; Table 1). In the unmatched population, patients treated with adjuvant HT plus RT were younger and had higher Gleason score distribution, higher rate of pT4 disease, higher mean number of nodes removed, and higher rates of positive surgical margins (all p ≤ 0.05). Patients receiving adjuvant RT plus HT
Discussion
Although the incidence of PCa nodal metastases has dramatically decreased in the PSA era [1], [29], LNI is still diagnosed in up to 40% of patients submitted to extended PLND [8], [10]. Historically, patients with LNI were considered affected by a systemic and noncurable disease. They were therefore not considered suitable for a surgical approach. However, several surgical series have shown that the long-term outcome of surgically treated patients with LNI is not invariably poor. Overall, 10-yr
Conclusions
We demonstrated that the adjuvant combination treatment with long-term HT and RT after RP is associated with significantly better long-term survival as compared with adjuvant HT alone in node-positive PCa. This survival benefit was demonstrated regardless of the extent of nodal invasion. These results reinforce the need for a multimodal approach in the treatment of node-positive PCa patients. Further long-term randomised trials are needed to confirm the role of adjuvant RT in patients with PCa
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