Antiandrogen hormonal therapy is frequently combined with different RT methods. Treatment concepts are often based on the results of randomized trials, particularly for high risk patients receiving EBRT as a single modality [9–11]. A longer duration of HT is usually favoured for high risk patients according to the results of prospective randomized trials, especially considering an adjuvant HT. Studies from the EORTC (European Organization for Research and Treatment of Cancer) and RTOG (Radiation Therapy Oncology Group) could demonstrate the survival benefit of the longer HT duration (three and two years) in comparison to a shorter duration (four and six months) [9, 10]. A secondary analysis of the RTOG 85–31 study reported improved survival for patients with HT treatment duration of more than five years (in comparison to one to five or less than one years) .
In contrast to HT, dose escalation studies did not show an overall survival benefit yet. A meta-analysis of randomized, controlled trials reported overall survival rates of 86% for both high-dose and low-dose radiotherapy , so that a relatively low total dose of 70.2Gy for patients treated with EBRT alone in this study can not explain a prognostic disadvantage in this respect. Accordingly - corresponding to the results of this study - randomized studies comparing a HDR-BT boost to EBRT in comparison to EBRT alone did not result in an overall survival benefit [15, 16].
Even six months of short-term neoadjuvant HT proved to be associated with increased overall survival in locally advanced prostate cancer (TROG, Trans-Tasman Radiation Oncology Group, 96.01 trial) . A Canadian multi-center trial comparing three months versus eight months of neoadjuvant HT in patients with localized prostate cancer has shown a significant overall survival benefit for high risk patients . However, a recently published analysis of this trial found the biochemical response to neoadjuvant HT to be the critical determinant of benefit in the setting of combined therapy. Multivariate analysis identified post-hormone PSA (PSA nadir before beginning of RT), Gleason score, initial PSA and T-stage, not HT duration, as independent predictors of biochemical disease free survival . The PSA level after 7 months of HT has also been found to be a strong independent predictor of survival in new metastatic prostate cancer in a Southwest Oncology Group (SWOG) trial . These results are in accordance with the results of our study, demonstrating the independent impact of prognostic factors and post-hormone PSA nadir on biochemical disease free survival. An additional independent prognostic risk factor was found in our patient population, namely a PSA progression during initial HT.
With a significant impact for biochemical recurrence free survival in multivariate analysis, the PSA nadir could probably become significant in multivariate analysis for disease and overall survival after a longer follow-up interval. Patients with PSA progression during initial HT appear to be a selection with extremely aggressive prostate cancer. These cancers have a considerable impact on short term survival rates in contrast to usually expected high disease specific survival rates after definitive curative RT (99% 5-year DSS for patients without initial HT in this study).
Two possible reasons can be attributed to this unfavourable prognosis. First, these tumours consist of a considerable amount of preselected aggressive cells that are resistant to antiandrogen therapy and apparently simultaneously resistant to radiation. Secondly, these tumours have a high metastatic potential, leading to the imminent threat to the patient’s life. A particularly unfavourable prognosis was found for patients with a PSA progression after only a few months of HT, indicating a fast resistance to treatment.
A comparable study of patients receiving irradiation for localized prostate cancer in case of a PSA progression after initial HT is presently not available in the literature. The survival rates that were found in our study after RT are comparable to studies evaluating the outcome of androgen independent prostate cancer without any recorded local treatment [23, 24]. Svatek et al.  reported a median disease specific and overall survival of 54 months and 51 months, respectively, for a population of 129 untreated consecutive patients with androgen independent prostate cancer. These data are well comparable to a median disease specific and overall survival of 54 months and 53 months in our study, so that a benefit of a local RT is not clear in this patient population. The decision for a local RT should be made considering this prognosis.
This is a retrospective analysis in a consecutively treated patient population, so that limitations exist due to a variety of underlying confounding factors. The generated hypothesis should be evaluated in other independent data sets. Imaging studies, like computed tomography of the abdomen, bone scan or choline-PET  might be useful not only at the time of the initial diagnosis but also before the decision for local RT even with smaller PSA levels, taking into account the high metastatic potential.