Starting in April of 2006, patients of all risk categories were treated as part of a prospective trial of SBRT for prostate cancer. Initially, patients with high-risk disease received external beam pelvic radiotherapy (EBRT) prior to a SBRT boost, but as data emerged from other studies that pelvic radiotherapy was of dubious value, patients began receiving SBRT alone [
21,
22]. This study is a retrospective analysis of these patients. Median follow up was 60 months (range, 8–84 mos).
Radiation treatment
From April 2006 through May 2011, 97 patients with clinically localized prostate cancer were treated with either EBRT followed by SBRT boost (n = 45) or SBRT alone (n = 52). Stage was determined by physical exam, bone scan and CT scans. All patients had high-risk disease as defined by the National Comprehensive Cancer Network (NCCN). Specifically, patients with a Gleason score ≥ 8 or a PSA > 20 ng/ml were identified as high-risk, as were patients with 2 or more intermediate risk factors (T stage > T2a, Gleason 7,or PSA >10 but <20). 50 patients received hormone therapy for a median of 5 months (range, 1–13 months). 45 patients received SBRT as a boost and 52 received SBRT alone. All patients were informed of potential treatment related risks and signed informed consent. Patient characteristics are summarized in Table
1.
Table 1
Patient characteristics at diagnosis
| 40-49 | 1 (1.0) | | 0 | 1 |
| 50-59 | 13 (13.4) | | 9 | 4 |
| 60-69 | 31 (32.0) | | 12 | 19 |
| 70-79 | 39 (40.2) | | 20 | 19 |
| 80-89 | 13 (13.4) | | 4 | 9 |
Mean (range) | | 70.0 (43.2-85.7) | 0.039 | 69.5 (50.6-84.4) | 70.3 (43.2-85.7) |
PSA level at treatment | | ng/mL | | | |
Combined | Mean (range) | 14.4 (0.59-53.1) | | 14.7 | 14.2 |
| Median | 11.5 | 0.0056 | 12 | 11.25 |
PSA level at diagnosis | | No. patients | | | |
| <4 ng/mL | 5 (5.2) | | 1 | 4 |
| 4-10 ng/mL | 30 (30.9) | | 17 | 13 |
| >10-20 ng/mL | 39 (40.2) | | 16 | 23 |
| >20 ng/mL | 23 (23.7) | | 11 | 12 |
Clinical stage | | | | | |
| T1c | 73 (75.2) | 0.22 | 33 | 40 |
| T2x | 2 (2.1) | | 2 | 0 |
| T2a | 18 (18.6) | | 6 | 12 |
| T2b | 2 (2.1) | | 2 | 0 |
| T2c | 2 (2.1) | | 2 | 0 |
Gleason score | | | 0.55 | | |
| 6 | 4 (4.1) | | 1 | 3 |
| 7 (3 + 4) | 15 (15.5) | | 7 | 8 |
| 7 (4 + 3) | 16 (16.5) | | 7 | 9 |
| 8 | 46 (47.4) | | 22 | 24 |
| 9 | 16 (16.5) | | 8 | 8 |
Hormone treatment | | | 0.34 | | |
| No | 43 (44.3) | | 17 | 26 |
| Yes | 54 (55.7) | | 28 | 26 |
RT treatment | | | 0.86 | | |
| SBRT | 52 (53.6) | | | |
| EBRT + SBRT | 45 (46.4) | | | |
High risk assessment: criteria | | | 0.95 | | |
Gleason ≥ 8 or PSA > 20 | | 83 (85.6) | | 45 | 38 |
Multiple adverse factors*: | | 14 (14.4) | | 0 | 14 |
Patients treated with EBRT followed by SBRT boost received an initial course of EBRT to a total dose of 45 Gy in 25 fractions of 1.8 Gy with 15-MV photons, administered on consecutive work days. A 3D-conformal four-field box plan was utilized to include the prostate and pelvic nodes. Image-guided SBRT boost was planned using MultiPlan® (Accuray, Inc., Sunnyvale, CA) inverse planning, and delivered using the CyberKnife (Accuray, Inc.) with motion tracking of internal fiducial seeds. A detailed description of the CyberKnife system can be found elsewhere [
23]. Patients underwent transperineal implantation of four fiducial seeds during EBRT, with two seeds placed at the prostate apex and two at the base. Treatment planning images were obtained one week after fiducial implantation to account for possible seed migration. Treatment was planned on CT images (1.5-mm cuts) with MRI fusion to soft tissue anatomy in the vast majority of patients. The prostate and proximal seminal vesicles were delineated to specify the gross tumor volume (GTV). The planning target volume (PTV) was created by adding a 5-mm margin to the GTV throughout, except posteriorly by the rectum where a tighter 3-mm margin was used. In all patients, the bladder, prostate, rectum, seminal vesicles and penile bulb were contoured, but the urethra was not identified.
The SBRT boost began two weeks after completion of EBRT, and was administered in three fractions over three consecutive days. SBRT planning began at the end of external beam radiation and accounted for the two week delay. Dose escalation was performed after at least 8 patients had 5 months of follow-up and no Grade 3 or higher toxicities were observed. The first 17 treated patients (38%) received a total SBRT boost dose of 18 Gy (3 fractions of 6 Gy each), the next 17 (38%) patients received 19.5 Gy (3 fractions of 6.5 Gy each) and the remaining 11 patients (24%) received 21 Gy (3 fractions of 7 Gy each). The initial dose of 18 Gy was based on high dose rate (HDR) brachytherapy boost treatment. The dose was prescribed to the 83-87% isodose line to cover 95% of the PTV, which included the proximal seminal vesicles. The mean number of beams was 152 (range, 142–176). The average Dmax was 21.42 Gy, 23.21 Gy, and 24.99 Gy for the 18, 19.5 and 21 Gy doses, respectively. Typical V105 values ranged from 78-82% of the PTV. The V75 was typically less than or equal to 4 cc for the bladder and 3 cc for the rectum. The mean D50 to the bladder and rectum was 41% and 43% of the Dmax dose, respectively. When feasible, without compromising overall treatment plan quality, the mean D50 to the penile bulb and testes was kept to less than 40% and 15% of the Dmax, respectively.
For each morning prior to SBRT, patients underwent a bowel prep including Dulcolax® (Boehringer Ingelheim, Germany) and a Fleet® Enema (C.B. Fleet Company, Inc., Lynchburg, VA). In addition, at least 15–20 minutes before treatment, all patients received 1500 mg of Amifostine (MedImmune, LLC Gaithersburg, MD), mixed in saline and instilled into the rectum.
For the patients who received SBRT alone, the dose was 35 Gy in 5 patients and 36.25 Gy in 47 patients. The dose was prescribed to the 83–87% line to cover 95% of the PTV. The PTV included the proximal seminal vesicles and was created by a similar expansion as with the boost patients. The mean number of beams was 158 (range 144–188). The rest of the dosimetric parameters were the same as the boost patients.
Follow-up schedule and toxicity assessment
All post-treatment time intervals were calculated from the time of SBRT completion. All patients were scheduled for follow-up three weeks after final treatment, four months later and then every six months thereafter. PSA tests were performed three months and six months after treatment, and every six months thereafter. Quality of life (QOL) was assessed using the Expanded Prostate Cancer Index Composite (EPIC) questionnaire [
24] at every follow-up visit during the first year and at 24 months. EPIC scores were calculated as defined in Wei et al. [
24]. In addition, toxicity was assessed using the Radiation Therapy Oncology Group (RTOG) urinary and rectal toxicity scale [
25] at every follow-up visit.