Phase 1 Trial of Neoadjuvant Radiation Therapy Before Prostatectomy for High-Risk Prostate Cancer

Duke Prostate Center, Duke Cancer Institute, Durham, North Carolina. Electronic address: .
International journal of radiation oncology, biology, physics (Impact Factor: 4.26). 06/2013; 87(1). DOI: 10.1016/j.ijrobp.2013.05.014
Source: PubMed


To evaluate, in a phase 1 study, the safety of neoadjuvant whole-pelvis radiation therapy (RT) administered immediately before radical prostatectomy in men with high-risk prostate cancer.
Twelve men enrolled and completed a phase 1 single-institution trial between 2006 and 2010. Eligibility required a previously untreated diagnosis of localized but high-risk prostate cancer. Median follow-up was 46 months (range, 14-74 months). Radiation therapy was dose-escalated in a 3 × 3 design with dose levels of 39.6, 45, 50.4, and 54 Gy. The pelvic lymph nodes were treated up to 45 Gy with any additional dose given to the prostate and seminal vesicles. Radical prostatectomy was performed 4-8 weeks after RT completion. Primary outcome measure was intraoperative and postoperative day-30 morbidity. Secondary measures included late morbidity and oncologic outcomes.
No intraoperative morbidity was seen. Chronic urinary grade 2+ toxicity occurred in 42%; 2 patients (17%) developed a symptomatic urethral stricture requiring dilation. Two-year actuarial biochemical recurrence-free survival was 67% (95% confidence interval 34%-86%). Patients with pT3 or positive surgical margin treated with neoadjuvant RT had a trend for improved biochemical recurrence-free survival compared with a historical cohort with similar adverse factors.
Neoadjuvant RT is feasible with moderate urinary morbidity. However, oncologic outcomes do not seem to be substantially different from those with selective postoperative RT. If this multimodal approach is further evaluated in a phase 2 setting, 54 Gy should be used in combination with neoadjuvant androgen deprivation therapy to improve biochemical outcomes.

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Available from: Judd W Moul, Mar 05, 2014
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    ABSTRACT: Objectives: Men with localized high-risk prostate cancer carry significant risk of prostate cancer-specific mortality. The best treatment approach to minimize this risk is unclear. In this review, we evaluate the role of radiation before and after radical prostatectomy. Methods and materials: A critical review of the literature was performed regarding the application of external radiation therapy (RT) in combination with prostatectomy for high-risk localized prostate cancer. Results: Up to 70% of men with high-risk localized disease may require adjuvant therapy because of adverse pathologic features or biochemical recurrence in the absence of systemic disease. The utility of adjuvant RT among men with adverse pathologic features are well established at least regarding minimizing biochemical recurrence risk. The optimal timing of salvage radiation is the subject of ongoing studies. Neoadjuvant RT requires further study but is a potentially attractive method because of decreased radiation field sizes and potential radiobiologic benefits of delivering RT before surgery. Salvage prostatectomy is effective at treating local recurrence after radiation but is associated with significant surgical morbidity. Conclusions: Combining local therapies including radical prostatectomy and RT can be a reasonable approach. Care should be taken at the initial presentation of high-risk localized prostate cancer to consider and plan for the likelihood of multimodality care.
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