Predictors for Late Urinary Toxicity After High-Dose Radiation Therapy for Localized Prostate Cancer

Volume 87  Number 2S  Supplement 2013 Whole-pelvic radiation therapy was not used. IPSS at baseline (i.e., before the initiation of ADT), 3, 6, 9, 12, and 24 months after IMRT were reviewed. Patients were evaluated in three groups of mild (baseline IPSS  7, n Z 124), moderate ( 8 and  19, n Z 70), and severe symptoms ( 20, n Z 22) according to the American Urological Association (AUA) classification. Toxicity was scored according to the Radiation Therapy Oncology Group morbidity grading scale. Results: The median follow-up was 34 months. GU mediations before any therapy were taken in 9.7% of the mild, 27.1% of the moderate, and 40.9% of the severe group (p Z 0.0002). Average planning target volumes (PTV) were 59.2 cc in the mild, 67.1 cc in the moderate, and 68.2 cc in the severe group (p Z 0.010). The average IPSS at baseline, 3, 6, 9, 12, and 24 months after IMRT were 3.5, 8.1, 5.4, 5.3, 5.4, 5.3 with the mild group, 12.6, 12.9, 10, 9.7, 10.1, 9.8 with the moderate group, and 23.8, 17.6, 13.5, 14.0, 13.8, 15.2 with the severe group. The rates of acute Grade 2 GU toxicities were 24.5%. No patients experienced acute  Grade 3 symptoms. The rates of acute Grade 2 GU toxicities were 16.9% with the mild, 31.4% with the moderate, and 36.4% with the severe group, and this AUA classification was associated with a higher incidence of acute GU toxicity (p < 0.0001). The rates of late Grade 2 and 3 GU toxicities were 8.3% and 1.2%. No patients experienced late Grade 4 toxicity. The AUA classification have no association with the risk of late GU toxicity (p Z 0.90). Conclusions: Patients with moderate to severe urinary symptoms can have improvement in urinary function after IMRT combined with ADT, whereas patients with mild symptoms may become worse slightly after treatment. Although patients can develop the acute GU toxicity with the increase of the AUA symptom classification, this has no association with the risk of late GU toxicity. Author Disclosure: N. Tomita: None. H. Tachibana: None. T. Kodaira: None. N. Soga: None. Y. Ogura: None. N. Hayashi: None.

2423 Successful Patient Acceptance of Randomization Within the Pace Study (Prostate Advances in Comparative Evidence) A. Tree,1 S. Aluwini,2 H. Bryant,1 E. Hall,3 L. Incrocci,2 I. Kaplan,4 P. Ostler,5 M. Sanda,4 A. Thompson,1 and N. van As1; 1Royal Marsden NHS Foundation Trust, London, United Kingdom, 2Erasmus Medical centre, Rotterdam, Netherlands, 3Institute of Cancer Research, London, United Kingdom, 4Beth Israel Deaconess Medical Centre, Boston, MA, 5 Mount Vernon Cancer Centre, London, United Kingdom Purpose/Objective(s): Robotic radiosurgery stereotactic body radiation therapy (SBRT) is successfully used to treat prostate cancer. As the a/b ratio for prostate cancer cells is likely to be <2 Gy, profound hypofractionation with SBRT should improve the therapeutic ratio. SBRT has been shown encouraging results, both in terms of biochemical relapse-free survival (b-RFS) and with low toxicity, but has not been compared to standard treatment options. Materials/Methods: The PACE study aims to answer two questions: Firstly, is robotic radiosurgery SBRT non-inferior to laparoscopic prostatectomy? Secondly, is robotic radiosurgery SBRT non-inferior to imageguided intensity modulated radiation therapy (IMRT)? The PACE study consists of two substudies: surgical candidates are randomized to prostatectomy vs robotic radiosurgery SBRT (Study A). Those who are not candidates for surgery are randomized to IMRT vs robotic radiosurgery SBRT (Study B). Eligible patients have T1c eT2c adenocarcinoma of the prostate, with Gleason 3+4 disease and a PSA of 20ng/mL or less. IMRT will be given to a dose of 78 Gy in 39 fractions without androgen deprivation therapy. Robotic radiosurgery SBRT can be given as 36.25 Gy in 5 fractions or 38 Gy in 4 fractions, both over 1-2 weeks. Radical prostatectomy must be done laparoscopically, robot-assistance is permitted. The study is led by a consortium of leading uro-oncologists and urologists. Data will be analyzed by the Institute of Cancer Research, UK and the study has been endorsed by Cancer Research UK and the National Cancer Research Network. Independent data monitoring and trial steering committees preside over the study. Over 1700 patients are required to rule out a 6% difference in b-RFS at 5 years, which is the primary end-point of

Poster Viewing Abstracts S365 the study. Measures of patient toxicity are also very important in localized prostate cancer and so toxicity and patient reported quality of life measurements are recorded regularly. Results: Recruitment has begun in 2 centers and is exceeding expectations. Within the first 5 months of recruitment at the first centre open, of 55 eligible patients, 52 were given patient information sheets and 28 consented to the study. Therefore the overall acceptance of randomization in this context is 54%. As expected, the acceptance of randomization rate is higher for study B (70%) compared with Study A (26%) but to date randomization milestones are being met. The major issues raised by patients who declined participation were based on having a bias towards specific therapy Conclusions: The PACE study is a ground-breaking study which will determine the role of robotic radiosurgery SBRT in organ-confined prostate cancer. Educating the patient on the therapeutic choices and the study hypothesis were instrumental to acceptance of participation in the study. Early recruitment at the first site open is encouraging but collaboration with many sites is needed to ensure success. Author Disclosure: A. Tree: E. Research Grant; The Royal Marsden NHS foundation trust is in receipt of an unrestricted educational grant to support a research fellow. The site is also participating in the PACE study which is supported by Accuray. H. Travel Expenses; Travel grant from Accuray to attend international conferences. S. Aluwini: None. H. Bryant: None. E. Hall: E. Research Grant; The Institute of Cancer research has received a grant from Accuray to support the data management and statistical analysis of the PACE trial. L. Incrocci: None. I. Kaplan: None. P. Ostler: H. Travel Expenses; Travel grants to facilitate attendance at international conferences. M. Sanda: None. A. Thompson: None. N. van As: E. Research Grant; Dr van As is the chief investigator of the PACE study which has received financial support from Accuray. H. Travel Expenses; Travel grants to facilitate attendance at international conferences.

2424 Predictors for Late Urinary Toxicity After High-Dose Radiation Therapy for Localized Prostate Cancer F. Garcia-Vicente, A. Zapatero, C. Martin de Vidales, G. Rodrı´guez, O. Leaman, A. Cruz-Conde, R. Bermudez, O. Lin˜an, L. Pe´rez, and J. Torres; Hospital Universitario La Princesa, Instituto de Investigacio´n Sanitaria Princesa, Madrid, Spain Purpose/Objective(s): To identify factors predictive for late urinary toxicity following high-dose three-dimensional and intensity modulated radiation therapy (IMRT) in patients with localized prostate cancer (PCa). Materials/Methods: This retrospective analysis included data from 671 consecutive patients with cT1-3 PCa treated with dose-escalation radiation therapy (median dose 79.7 Gy). Eligibility criteria were radiation dose >72 Gy, no pelvic radiation therapy and a minimum follow-up higher than 12 months. 437 patients were treated with 3 three-dimensional conformal radiation therapy (3DCRT) and 234 patients with IMRT using intra-prostate gold fiducial markers. Two hundred and fifty six patients also received long-term androgen deprivation (AD) for high-risk disease. Acute and late toxicities were classified and graded according to the Common Terminology Criteria for Adverse Events version 4.0 definition. Univariate and multivariate analysis (MVA) were performed to identify variables significantly associated with late GU toxicity. Analyses were carried out using statistical software. Results: The median follow-up was 58 months (range, 12-170 months). The incidence of late GU toxicity was significantly reduced in patients treated with IMRT compared to those treated with 3DCRT despite of the use of higher radiation dose. The rates of late grade 2 or more GU complications for IMRT and 3DCRT were 3.0% and 13.7% (p Z 0.000), respectively, with only 7 patients (1.0%) experiencing grade 3 complications. On MVA and adjusting by treatment type (3D-CRT or IMRT), prior transurethral resection of the prostate (TURP) (odds ratio Z 0.285; p Z 0.001), a reduce bladder volume(odds ratio Z 0.998 per cubic centimeter of bladder filling; p Z 0.051) and acute GU toxicity (odds ratio Z 0.367, p Z 0.028), were significantly associated with a higher risk of late GU

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toxicity, whereas long-term AD was correlated with a significantly decreased risk (odds ratio Z 2.291; p Z 0.023). Conclusions: The present study with a longer follow-up, confirms our previous data reporting a protecting effect of long-term hormones in late urinary toxicity after radiation therapy. These data also corroborate results from other institutions showing that the patient’s ability to fill the bladder has a major impact on late urinary toxicity. Despite the lower follow-up of the cohort of the patients treated with IMRT the reduction of GU toxicity is encouraging. Author Disclosure: F. Garcia-Vicente: None. A. Zapatero: None. C. Martin de Vidales: None. G. Rodrı´guez: None. O. Leaman: None. A. Cruz-Conde: None. R. Bermudez: None. O. Lin˜an: None. L. Pe´rez: None. J. Torres: None.

Oncology, Kobe University Graduate School of Medicine, Kobe, Japan, 2 Department of Radiation Oncology, Kobe Minimally Invasive Cancer Center, Kobe, Japan, 3Department of Urology, Kobe University Graduate School of Medicine, Kobe, Japan

2425 A New Dietary and Laxative Protocol Reduces Rectal Distension and Acute Rectal Toxicity in Prostate Cancer Patients Treated by Radiation Therapy J. Lozano, O. Pera, P. Foro, J. Lio, I. Membrive, A. Reig, X. Sanz, N. Rodrı´guez, E. Ferna´ndez-Velilla, and M. Algara; Parc de Salut Mar. Hospital de l’Esperanc¸a. Servei d’Oncologia Radiotera`pica, Barcelona, Spain Purpose/Objective(s): The position of PTV in prostate cancer radiation therapy is affected by rectal distension. A distended rectum at the planning CT scan reduces disease control in this scenario. The introduction of dietary and laxative protocols significantly decreases feces and rectal gas and reduces rectum distension at the CT planning scan. We tried to work with foreign dietary protocols but they had not result in our environment. As a result we have implemented a local protocol in our population of prostate cancer patients treated by external-beam radiation therapy. Objectives are to study the feasibility of the new protocol and to compare rectal distension and rectal toxicity in patients before and after the implementation of the protocol. Materials/Methods: We designed a “Mediterranean adaptation” of the Dutch protocol published by Smitsmans et al. The protocol consists of a local antiflatulent diet and the intake of 1 g/5 mL of magnesium hydroxide daily, starting 4 days before acquisition of the planning CT scan and 4 days before radiation therapy treatment up to the end of treatment. Patients were treated by three-dimensional conformal radiation therapy or intensity-modulated radiation therapy without image-guided radiation therapy techniques. CT planning scans of patients before the implementation of the protocol were compared against scans of patients subject to the new protocol. Rectal volume between the two groups was compared. Rectal distension was assessed calculating the average of the CrossSectional Area (CSA defined as the rectal volume divided by the length). Rectal toxicity was assessed according to RTOG scoring criteria. Results: Eighty-seven no-protocol patients were compared against 92 patients subject to the new protocol. The rectal distension were significantly lower among the protocol patients with an average CSA of 7.39 (+/- 0.54) cm2 vs 9.29 (+/- 0.92) cm2; a Z 0.05, p Z 0.0027. On the other hand, grade 3 rectal toxicity (rectal bleeding during radiation therapy), were significantly lower among the protocol patients (3% vs13%) a Z 0.05, p Z 0.034. Conclusions: This protocol is feasible in our population and reduces rectum distension at the CT planning scan. In addition rectal bleeding during radiation therapy is significantly lower in protocol patients. Author Disclosure: J. Lozano: None. O. Pera: None. P. Foro: None. J. Lio: None. I. Membrive: None. A. Reig: None. X. Sanz: None. N. Rodrı´guez: None. E. Ferna´ndez-Velilla: None. M. Algara: None.

2426 Efficacy of Salvage Radiation Therapy in Men With Biochemical Recurrence After Radical Prostatectomy: A Comparison With Endocrine Therapy N. Suleiman,1 K. Yoshida,1 D. Miyawaki,1 Y. Ejima,1 H. Nishimura,2 J. Furukawa,3 M. Fujisawa,3 and R. Sasaki1; 1Division of Radiation

Purpose/Objective(s): Most of the recurrences after radical prostatectomy (RP) are detected only by a rise in the prostate-specific antigen (PSA) level without a radiographic recurrence site. For such men it is unknown whether salvage radiation therapy (SRT) to the prostate bed confers a survival benefit compared with systemic therapy. The standard treatment for PSA failure after RP has not yet been determined. This study aims to compare the outcomes of SRT and endocrine therapy (ET) for PSA failure after RP with regard to biochemical control, rate of clinical failure and survival. Materials/Methods: A cohort of 80 men undergoing prostatectomy from 2001 to 2009 who experienced postoperative PSA failure and received salvage treatment were retrospectively reviewed. Median age at prostatectomy was 69 years old. The majority had intermediate-risk (32%) or high-risk (66%) prostate cancer. As salvage treatment, 31 patients (39%) received SRT and 49 patients (61%) received ET. For ET, 28 patients (57%) received luteinizing hormone-releasing hormone, 9 patients (18%) received androgen blockade and 12 patients (24%) received MAB therapy. SRT was directed to the prostatic fossa with a median dose of 64.8 Gy (range, 60-70 Gy) in 30-36 fractions. Results: After a median follow-up of 88 months after prostatectomy and 61 months after recurrence, 3 men (4%) died, including 1 who died from prostate cancer and 2 from other cause. The 10-year overall survival rate for SRT group and ET group were 96% and 90%, respectively. The 10-year clinical failure-free rate for SRT group and ET group were 100% and 91%, respectively. The 10-year biochemical failure-free rate for SRT group and ET group were 59% and 84%, respectively. The SRT group had significantly poorer biochemical failure-free rate (p Z 0.002). Eleven patients (35%) from the SRT group who failed to maintain durable PSA control were treated with adjuvant ET. The median duration of ET in the SRT group was 50 months compared to 61 months in the ET group. There were no significant differences in outcomes based on clinical and pathology findings in both groups. No grade 3 or worse RT-related toxicity was observed. Conclusions: To date, the only potentially curative treatment option that exists for PSA failure after RP is SRT. In our study, the biochemical failure-free rate in the SRT group was higher than the ET group. However, both clinical failure-free and overall survival rates in the SRT group became comparable to those in the ET group by adding ET with shorter duration to only 11 patients (35%) who experienced 2nd biochemical failure. No severe RT-related toxicity was observed. Our results indicate that SRT is an effective and safe treatment tool for men with biochemical failure after prostatectomy. These preliminary findings should be validated in randomized controlled trials comparing SRT and ET. Author Disclosure: N. Suleiman: None. K. Yoshida: None. D. Miyawaki: None. Y. Ejima: None. H. Nishimura: None. J. Furukawa: None. M. Fujisawa: None. R. Sasaki: None.

2427 Dosimetric and Clinical Predictors of Acute Urinary Symptoms After Radiation Therapy for Prostate Cancer: Preliminary Results of a Prospective Cohort Study (DUE-01) V. Carillo,1 C. Cozzarini,2 T. Rancati,3 B. Avuzzi,4 P. Franco,5 C. Degli Esposti,6 G. Girelli,7 V. Vavassori,8 R. Valdagni,3 and C. Fiorino1; 1 Medical Physics, San Raffaele Scientific Institute, Milano, Italy, Milan, Italy, 2Radiotherapy, San Raffaele Scientific Institute, Milano, Italy, Milan, Italy, 3Prostate Cancer Program, Scientific Director’s Office, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, Milan, Italy, 4 Radiotherapy 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, Milan, Italy, 5Radiotherapy, USL Aosta, Aosta, Italy, Aosta, Italy, 6 Radiotherapy, Bellaria Hospital, Bologna, Italy, Bologna, Italy, 7 Radiotherapy, Ivrea Hospital, Ivrea, Italy, Ivrea, Italy, 8Radiotherapy, Cliniche Humanitas Gavazzeni, Bergamo, Bergamo, Italy