Elsevier

European Urology

Volume 59, Issue 5, May 2011, Pages 832-840
European Urology

Prostate Cancer
Combination of Adjuvant Hormonal and Radiation Therapy Significantly Prolongs Survival of Patients With pT2–4 pN+ Prostate Cancer: Results of a Matched Analysis

https://doi.org/10.1016/j.eururo.2011.02.024Get rights and content

Abstract

Background

Previous prospective randomised trials have shown a positive impact of adjuvant radiation therapy (RT) in patients with locally advanced prostate cancer. However, none of these trials included patients with lymph node invasion (LNI).

Objective

The aim of this study was to assess the impact of combination adjuvant hormonal therapy (HT) and RT on the survival of patients with prostate cancer and histologically documented lymph node metastases (pN+).

Design, setting, and participants

Data on 703 consecutive patients with LNI treated with radical prostatectomy, pelvic lymph node dissection, and adjuvant treatments between September 1986 and November 2002 at two large academic institutions were reviewed.

Measurements

For study purposes, patients treated with adjuvant HT plus RT and patients treated with adjuvant HT alone were matched for age at surgery, pathologic T stage and Gleason score, number of nodes removed, surgical margin status, and length of follow-up. Differences in cancer-specific survival (CSS) and overall survival (OS) were compared using the Kaplan-Meier method and life table analyses.

Results and limitations

Following the matching process, 117 pT2–4 pN1 patients of 171 (68.4%) treated with adjuvant HT plus RT (group 1) were compared with 247 pT2–4 pN1 patients of 532 (46.4%) receiving adjuvant HT alone (group 2). After matching, the two groups of patients were comparable in terms of pre- and postoperative characteristics (all p ≥ 0.07). Mean follow-up was 100.8 mo (median: 95.1 mo; range: 3.5–229.3 mo). Overall, prostate CSS and OS rates at 5, 8, and 10 yr were 90%, 82%, and 75%, and 85%, 70%, and 60%, respectively. Patients treated with adjuvant RT plus HT had significantly higher CSS and OS rates compared with patients treated with HT alone at 5, 8, and 10 yr after surgery (95%, 91%, and 86% vs 88%, 78%, and 70%, and 90%, 84%, and 74% vs 82%, 65%, and 55%, respectively; p = 0.004 and p < 0.001, respectively). Similarly, higher survival rates associated with the combination of HT plus RT were found when patients were stratified according to the extent of nodal invasion (namely, two or fewer vs more than two positive nodes; all p ≤ 0.006). Lack of standardised HT and RT protocols represents the main limitations of our retrospective study.

Conclusions

Adjuvant RT plus HT significantly improved CSS and OS of pT2–4 pN1 patients, regardless of the extent of nodal invasion. These results reinforce the need for a multimodal approach in the treatment of node-positive prostate cancer.

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.

Section snippets

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

References (32)

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