Single blind randomized Phase III trial to investigate the benefit of a focal lesion ablative microboost in prostate cancer (FLAME-trial): study protocol for a randomized controlled trial

Background: The treatment results of external beam radiotherapy for intermediate and high risk prostate cancer patients are insufficient with five-year biochemical relapse rates of approximately 35%. Several randomized trials have shown that dose escalation to the entire prostate improves biochemical disease free survival. However, further dose escalation to the whole gland is limited due to an unacceptable high risk of acute and late toxicity. Moreover, local recurrences often originate at the location of the macroscopic tumor, so boosting the radiation dose at the macroscopic tumor within the prostate might increase local control. A reduction of distant metastases and improved survival can be expected by reducing local failure. The aim of this study is to investigate the benefit of an ablative microboost to the macroscopic tumor within the prostate in patients treated with external beam radiotherapy for prostate cancer.Methods/Design: The FLAME-trial (Focal Lesion Ablative Microboost in prostatE cancer) is a single blind randomized controlled phase III trial. We aim to include 566 patients (283 per treatment arm) with intermediate or high risk adenocarcinoma of the prostate who are scheduled for external beam radiotherapy using fiducial markers for position verification. With this number of patients, the expected increase in five-year freedom from biochemical failure rate of 10% can be detected with a power of 80%. Patients allocated to the standard arm receive a dose of 77 Gy in 35 fractions to the entire prostate and patients in the experimental arm receive 77 Gy to the entire prostate and an additional integrated microboost to the macroscopic tumor of 95 Gy in 35 fractions. The secondary outcome measures include treatment-related toxicity, quality of life and disease-specific survival. Furthermore, by localizing the recurrent tumors within the prostate during follow-up and correlating this with the delivered dose, we can obtain accurate dose-effect information for both the macroscopic tumor and subclinical disease in prostate cancer. The rationale, study design and the first 50 patients included are described.Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Patterns of outcome and toxicity after salvage prostatectomy, salvage cryosurgery and salvage brachytherapy for prostate cancer recurrences after radiation therapy:a multi-center experience and literature review

<p>Current salvage treatments for recurrent prostate cancer after primary radiation therapy include radical prostatectomy, cryosurgery and brachytherapy. Because toxicity and failure rates are considerable, salvage treatments are not commonly performed. As most centers perform only one preferred salvage technique, the literature only describes single-center outcomes from a single salvage technique with a limited number of patients. In this overview, five high-volume Dutch centers describe their toxicity and outcome data using different salvage techniques. This provides a view on how salvage is performed in clinical practice in the Netherlands.</p><p>A total of 129 patients from five different centers in the Netherlands were retrospectively analyzed. Biochemical failure (BF) was defined as PSA > 0.1 ng/ml for the salvage prostatectomy group (n = 44) and PSA nadir + 2.0 ng/ml (Phoenix definition) for the salvage cryosurgery (n = 54) and salvage brachytherapy group (n = 31). Toxicity was scored according to the Common Toxicity Criteria for Adverse events (CTCAE v3.0).</p><p>BF occurred in 25 (81 %) patients in the brachytherapy group (mean follow-up 29 +/- A 24 months), 29 (66 %) patients in the prostatectomy group (mean follow-up 22 +/- A 25 months) and 33 (61 %) patients in the cryosurgery group (mean follow-up 14 +/- A 11 months). Severe (grade > 3) genitourinary and gastrointestinal toxicity was observed in up to 30 % of patients in all three groups.</p><p>This overview shows clinical practice of prostate cancer salvage. Significant failure and toxicity rates are observed, regardless of salvage technique. Patients should be selected with great care before offering these salvage treatment strategies.</p>