The Relationship Between the Occurrence of Bone Metastases and Dose/Volume of Prior Prostate Radiation Therapy in Patients With Localized Prostate Cancer

Purpose/Objective(s): The RTOG 94-13 phase III trial showed that Whole Pelvic nodal Radiation therapy (WPRT) improved progression-free survival (including distant failures). We hypothesized that WPRT may have a beneficial impact on pelvic bone metastatic burden in localized prostate cancer at high risk of harboring bone micrometastases. Materials/Methods: We reviewed the charts of 228 metastatic prostate cancer patients who were referred to our facility between 01/1981 and 07/ 2012. One hundred and thirteen of the 228 patients (49.6%) who were M0 at diagnosis and had a bone scintigraphy at time of the occurrence of first bone metastases (B-mets) were selected. B-mets in pelvic nodal fields were defined as any B-met found between L5-S1 and the upper border of pubic symphysis. B-mets in prostate fields were defined as any B-met beyond pelvic B-mets and above the lesser trochanter of femoral heads. The number and the location (in-field vs. out-field) of B-mets were compared with respect to the prior treatment delivered to the prostate using Chi tests. Results: Group 1 (No pelvic RT, n Z 57): 17 patients (23.3%) had radical prostatectomy (RP), 1 patient had brachytherapy, 33 patients (29.2%) had hormones and 7 patients (6.2%) a bilateral orchiectomy. Group 2 (External pelvic RT, n Z 56): 39 patients (53.4%) underwent RT while 17 patients (23.3%) had RP followed by RT. Forty patients (70.2%) and 26 patients (46.4%) had hormones in groups 1 and 2, respectively (p Z 0.01). The median doses to the pelvis and the prostate bed were 46Gy [46-60] and 70Gy [60-80], respectively. The mean PSA values at the time of distant failure were 201.5 370.1 ng/mL and 165.6 698.8 ng/mL in groups 1 and 2, respectively (pZ 0.25). The median times between the diagnosis of prostate cancer and the occurrence of B-mets were 3.6y [0.7-18.7] and 5.0y [1-20.6] in groups 1 and 2, respectively (p Z 0.06). Eighty three patients (73.5%) developed 2 out-field B-mets, 42 patients (73.7%) in group 1 and 41 patients (73.2%) in group 2 (pZ 0.955). Eighteen (32.1%) patients treated in group 2 developed 2 in-field B-mets versus 33 patients (57.9%) in group 1 (p Z 0.006). This difference was more pronounced in prostate fields ( 2 B-mets: 1 (1.8%) in group 2 vs. 19 (33.3%) in group 1, p<0.0001) whereas there was no difference in the number of B-mets in pelvic fields (( 2B-mets: 17 (30.4%) in group 2 vs. 24 (42.1%) in group 1, p Z 0.194). In multivariate logistic regression analysis, patients treated with prior RT were more likely to develop 0-1 pelvic B-mets (OR Z 0.3 [95% CI: 0.12-0.77], p Z 0.011) (adjusted on the number of out-field Bmets and D’Amico risk groups). Conclusions: We found unsuspected stochastic benefits from external pelvic radiation therapy on distant failure in localized prostate cancer patients. B-met radio-prevention with external RT needs to be validated through a randomized phase III trial. Author Disclosure: G. Crehange: None. G. Laporte: None. C. Dalban: None. E. Martin: None. A. Cochet: None. L. Cormier: None. C. Mirjolet: None. I. Desmoulins: None. S. Ladoire: None. P. Maingon: None.