Long-term outcomes of prostate radiotherapy for newly-diagnosed metastatic prostate cancer.

BACKGROUND: In patients presenting with metastatic prostate cancer, the role of local therapy is evolving. Two recently reported large-scale randomized trials suggest that radiotherapy (RT) directed at the prostate improves overall survival (OS) in patients with low metastatic burden. We reviewed the experience of prostate RT in this setting at our center. METHODS: The study population consisted of men with newly-diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) referred to a comprehensive cancer center between 2005 and 2015 and treated initially with androgen deprivation therapy. Patients were eligible for inclusion if they received (1) prostate RT with biological effective dose (BED) at least that of a course of 40 Gy in 15 fractions or (2) no prostate RT. The association between receipt of prostate RT and OS was studied. OS was estimated using the Kaplan-Meier method and Cox regression was used to identify factors associated with OS. RESULTS: The cohort consisted of 410 patients, of whom 128 received prostate RT. Median follow-up 61.0 months. On univariate analysis, receipt of prostate RT was associated with improved OS (HR 0.59, 95% CI 0.45-0.77, p = 0.0001). Median OS in those patients receiving prostate RT was 47.4 months versus 26.3 months in those not receiving prostate RT. In a multivariate Cox model, receipt of prostate RT remained associated with improved OS (HR 0.69, 95% CI 0.50-0.94, p = 0.02). In those treated with prostate RT, increasing BED was also associated with improved OS (HR 0.87 per 10 Gy increase, 95% CI 0.76-0.99, p = 0.03). CONCLUSIONS: This cohort represents the largest single-center experience of primary tumor-directed RT in mHSPC reported to date. In this population, receipt of prostate RT was associated with improved OS and the magnitude of the OS benefit was clinically significant. The possibility of an RT dose-response gradient in this setting merits further study.

Reducing errors in prostate tracking with an improved fiducial implantation protocol for CyberKnife based stereotactic body radiotherapy (SBRT).

PURPOSE: Ultra-hypofractionated radiotherapy with SBRT is an established technique for treating localized prostate cancer. CyberKnife based SBRT requires implantation of fiducial markers for soft tissue target tracking by the orthogonal KV X-ray imaging system. The spatial distribution of fiducial markers must allow accurate calculation of a 3D transformation that describes the position of the prostate within the reference frame of the planning CT scan. Accuray provides a fiducial implantation guideline for tracking soft tissue lesions. Despite using the guideline we experienced an unacceptably high rate of rotational tracking failure due to problems with fiducial placement. We adapted the Accuray guideline to prostate SBRT for improved fiducial placement and more reliable target tracking.Methods and materials: 54 patients with prostate adenocarcinoma were treated with ultra-hypofractionated radiotherapy on CyberKnife. Patients had platinum fiducial markers implanted transrectally under ultrasound guidance by a Radiologist. For the first 26 patients, fiducial markers were positioned following the Accuray fiducial placement guidelines for soft tissue lesions (cohort 1). The initial rotational tracking error rate was unacceptably high (23%). On review, inappropriate fiducial placement was identified as the cause of error (especially insufficient spacing between seeds). In October 2016 we developed a seed placement protocol specifically for implanting fiducial markers within the prostate and a second cohort of patients was treated thereafter (cohort 2, 28 patients). The stipulations of the original guideline are maintained while the modified protocol requires that 4 fiducial markers be implanted in the postero-lateral peripheral zone in a single coronal plane. RESULTS: In cohort 1, patients had a median age of 64 years (50 - 74), PSA of 6.6mcg/L (1.1 - 14.7), and prostate volume of 56 cc (22 - 125), while in cohort 2 they had a mean age of 65 years (53 - 75), PSA of 6.2 mcg/L (1 - 12) and prostate volume of 47 cc (21 - 106). The fiducial markers were easily visualized and there were no cases of urosepsis related to fiducial implantation. In 6 of 26 patients (23%) from cohort 1, only translational mapping without accurate spatial rotations could be calculated. After adopting the prostate specific fiducial implantation protocol, rotational tracking error was eliminated. Accurate 6 degree tracking (accounting for translations and rotations) was achieved in all 28 patients from cohort 2. Using an in-house computer script we analyzed the dose distributions resulting from rotational misalignments of -10, -5, -3, 3, 5, and 10 degrees along all three rotational axes (pitch, roll and yaw). Rotational misalignments result in decreased minimum dose to the PTV and increased maximum dose to OARs. CONCLUSION: Implementing a prostate specific fiducial placement protocol for SBRT significantly improved our ability to track prostate motion in 6 degrees 77% to 100% reliability. Failure to track rotations can potentially lead to underdosing and overdosing of portions of the prostate and OARs respectively.