P108 Helical tomotherapy in prostate cancer: Minimizing toxicity

posters / european urology supplements 11 (2012) 191–235

Material & Methods: We reviewed the clinical records of all pts with BM referred at Santa Chiara Hospital ORDs from 1994 to 2011: since DOC was introduced into our clinical practice in 2003, we separately evaluated two periods (P1: 1994–2002; P2: 2003–2011). We limited our search to male pts to avoid the bias due to the incidence of BM from breast cancer. For each pt we assess the primary tumor diagnosis and in the case of PC diagnosis we recorded all relevant issues of the clinical history. Results: In the study period 490 males with BM were referred to our ORDs (P1 = 241 pts; P2 = 249). The most frequent recognized primary tumor was lung cancer, with a similar percentage of BM for P1 and P2 (58.9 vs 60.6%). Concerning PC we collected a series of 9 pts with BM: 2 pts in P1 and 7 in P2 (0.8% and 2.8%, respectively). The median age at the diagnosis of PC was 64 yrs (range 65–78). All but 2 pts had a CRPC: among them, 6 pts developed BM during or after a DOC-based chemotherapy and 1 before first line DOC start. The median interval from the PC diagnosis and the achievement of CRPC was 25 mos (range 5–84) while the appearance of BM was documented after 0–111 mos (median 36) from diagnosis. The median survival after BM was 8 wks (range 1–54). Conclusions: Our data appear to confirm that: 1) the BM from PC pts are more frequent than in the past; 2) this finding could be related to a survival improvement due to DOC introduction in the clinical practice; 3) a special attention should be reserved to the appearance of neurological symptoms in a long-term CRPC survivor due to a possible relation with BM. P107 Dosimetric evaluation of the feasibility of an intraprostatic boost according to gross-tumor-volumes (GTVs) location for prostate cancer patients treated with combined external beam radiotherapy (EBRT) and high-dose-rate brachytherapy (HDR-BT) J. Helou1 , R. Verstraet2 , P. Blanchard1 , A. Rodriguez2 , D. Lefkopoulos2 , J. Bourhis1 , L. Calmel2 , F. Azoury1 , A. Bossi1 . 1 Institut Gustave Roussy, Dept. of Radiation Oncology, Villejuif, France; 2 Institut Gustave Roussy, Dept. of Medical Physics, Villejuif, France Introduction & Objectives: HDR-BT allows for dose escalation to the whole prostatic gland volume and for a selective intraprostatic GTV boost. Short and long term urethral and rectal toxicity may limit intra-prostatic dose escalation. Our study aims to identify the dosimetric feasibility and limitations of an intra-prostatic boost to different GTVs locations according to 4 dose levels. Material & Methods: The study was conducted on 18 patients treated on an institutional protocol of combined HDR-BT single fraction of 9.5 Gy (= Prescribed dose, PD) followed by EBRT delivered with Intensity modulated technique (IMRT). The GTV locations studied for the intra-prostatic boost were; posterolateral, total posterior, antero-lateral, total anterior and 3 volumes in the apical zone characterized by different heights in the apex-base direction: 15, 20 and 25 mm. All patients had a standard optimization with the 90% of the CTV receiving 100 to 105% of the PD. Four boost-dose levels were studied: 100%, 120%, 135% and 150% of the PD. The urethral and rectal D0.1 and D0.5 cc were reported for every dose level. Results: An intraprostatic dose escalation on the postero-lateral GTV had no significant impact on the urethral D0.1 cc and D0.5 cc, while a significant increase in the rectal D0.1 cc (74, 77, 80 and 84% for every dose level respectively) and D0.5 cc (68, 70, 72 and 75%) was noted (p < 0.05). Similarly, a boost on the total posterior GTV had a significant impact on the rectal D0.1 cc (74, 77, 78 and 81%) and D0.5 cc (67, 70, 71 and 73%) (p < 0.05), while the urethral D0.1 cc increased significantly only for a boost of 150% (p = 0.013). An antero-lateral and total

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anterior boost significantly increased the urethral D0.1 cc for a dose ≥135% (p = 0.007 and 0.01 respectively) while significantly decreasing the rectal doses. No significant impact of an apical dose escalation was seen on the urethra whereas the rectal doses increased significantly for a boost ≥135% (p < 0.05). No major increase on rectal and urethral doses was observed with the 120 % boost level except for the posterior GTV (D0.1 cc = 77%). However, this increase is still within acceptable limits. Conclusions: Delivering an intra-prostatic boost dose of 120 % of the PD with HDR-BT is feasible and safe regardless of the GTV location. Further increases of the intra-prostatic boost dose may be possible only by carefully evaluating the spatial distribution of the GTV as well as the rectal and urethral doses. P108 Helical tomotherapy in prostate cancer: Minimizing toxicity C. Acebedo1 , J.L. Lopez ´ Guerra1 , E. Rivin Del Campo2 , R. Matute1 , N. Isa1 , F. Puebla1 , M. Russo3 , A. Sanchez-Reyes4 , C. Beltran ´ 1, 1 5 1 J. Jaen ´ , H. Marsiglia . Instituto Madrile˜ no De Oncolog´ıa/Grupo IMO, Dept. of Radiation Oncology, Madrid, Spain; 2 Hospital General De Elche. ERESA, Dept. of Radiation Oncology, Elche, Spain; 3 Radiomedicine Institute IRAM, Dept. of Radiation Oncology, Santiago, Chile; 4 Instituto Madrile˜ no De Oncolog´ıa/Grupo IMO, Dept. of Radiation Physics, Madrid, Spain; 5 Institut De Canc´erologie Gustave Roussy, Dept. of Radiation Oncology, Villejuif, Paris, France Introduction & Objectives: Radiation-induced toxicity is an important adverse event that affects most patients receiving radiation therapy (RT) for prostate cancer (PC), especially for those who underwent prior treatment such as surgery. Intensity modulated radiation therapy has been shown to decrease acute toxicity. We present the clinical results of intensity-modulated radiation therapy with helical tomotherapy (HT) for clinically localized and recurrent PC, as well as post-prostatectomy adjuvant treatment. Material & Methods: From May 2006 to January 2011, 70 cT1-T3 cN0 cM0 PC patients were treated with HT (primary diagnosis, n = 48; post-prostatectomy biochemical recurrence, n = 15; post-brachytherapy biochemical recurrence, n = 2; and post-prostatectomy adjuvance, n = 5). The dose prescribed to the prostate ranged between 72–78 Gy, except for one case (post-brachytherapy recurrence, 66 Gy) with conventional fractionation (2 Gy/fraction). The seminal vesicles received between 50–56 Gy, the surgical bed 66–74 Gy, and the pelvic lymph nodes 46–50.4 Gy (n = 20), respectively when applicable, with conventional fractionation. Minimum follow-up was 3 months. Demographic, tumor and treatment characteristics were recorded and analyzed. The follow-up was calculated from the HT start date to the last contact date. For patients with a primary diagnosis or those receiving adjuvant HT, survival time was measured from the diagnosis date to the last contact date for alive patients or the date of death if the patient had died. For patients receiving HT for biochemical recurrence, survival time was measured from the recurrence diagnosis date to the last contact date for alive patients or the date of death for deceased patients. Genitourinary (GU) and gastrointestinal (GI) toxicity was scored using the Radiation Therapy Oncology Group (RTOG) scoring system. Results: The median age was 68 years (range 51–87 years). The median follow-up was 37 months (range 3–74 months). The mean initial Gleason score was 6±1 and the mean initial PSA was 17.11±35 ng/ml. The mean total dose was 75.48±2.88 Gy for prostate, 54.04±1.13 Gy for seminal vesicles, 67.8±3.7 Gy for the surgical bed, and 46.32±1.4 for pelvic lymph nodes. The mean vesical and rectal volumes were 149±90 cc and 79.05±28 cc, respectively. For patients with a primary diagnosis or those receiving adjuvant HT, median overall survival was 45 months (range, 8–82 months). For patients receiving HT for

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posters / european urology supplements 11 (2012) 191–235

biochemical recurrence, overall survival was 24 months (range, 3–73 months). Overall, only 3 patients died, and none of them due to a cancer-related cause. Local recurrence was seen in 1 patient which had been treated for a biochemical recurrence after initial prostatectomy. Regional recurrence and bone disease only occurred in one patient with primary intermediate risk PC. The rates of acute grade 2 gastrointestinal (GI) and genitourinary (GU) toxicities were 13% and 10 %, respectively. Only one patient experienced acute grade 3 GU toxicity. The rates of late grade 2 GI toxicities were 1.5%, and those of late grade 2 GU toxicities were 1.2%. No patients experienced late Grade ≥3 toxicity. Conclusions: This preliminary report confirms the feasibility of HT. Tomotherapy is associated with a very low risk of toxicity and a low recurrence rate. Acute and late gastrointestinal and genitourinary toxicities were tolerable without any grade >3 side effects. Further research is necessary to assess definitive late toxicity and tumor control outcome.

Advanced prostate cancer P109 Efficacy and safety of a 3-monthly depot formulation of degarelix compared with goserelin in prostate cancer B. Tombal1 , T.L.J. Tammela2 , J.M. Wolff3 , H. Payne4 , E.D. Crawford5 , N. Shore6 , M.C. Gittelman7 , T.K. Olesen8 , B. Persson9 , L. Klotz10 . 1 Cliniques Universitaires Saint Luc/Universit´e Catholique De Louvain, Service D’Urologie, Brussels, Belgium; 2 Tampere University Hospital, Division of Urology, Tampere, Finland; 3 Viersen General Hospital, Dept. of Urology, Viersen, Germany; 4 University College Hospital, Dept. of Clinical Oncology, London, United Kingdom; 5 University of Colorado Cancer Center, Dept. of Urologic Oncology, Aurora, United States of America; 6 Carolina Urologic Research Center and Atlantic Urology Clinics, Dept. of Urology, Myrtle Beach, United States of America; 7 South Florida Medical Research, Dept. of Urology, Aventura, United States of America; 8 Ferring Pharmaceuticals, Clinical R&D, Copenhagen, Denmark; 9 Ferring Pharmaceuticals, Medical Sciences, St-Prex, Switzerland; 10 University of Toronto, Dept. of Surgery, Toronto, Canada Introduction & Objectives: Once-monthly degarelix 240/80 mg significantly improved prostate-specific antigen (PSA) progression-free survival vs. leuprolide in prostate cancer (PCa). This 1-year, open-label, randomised study (CS35, NCT00946920) evaluated a 3-monthly degarelix formulation. Material & Methods: Patients received degarelix (240 mg, then 480 mg every 3 months) or goserelin (3.6 mg, then 10.8 mg every 3 months) ± bicalutamide. Co-primary endpoints were cumulative probability of testosterone ≤0.5 ng/mL: from Days 3–364 for degarelix vs. goserelin and from Days 28–364 with degarelix. Results: Overall, 848 patients received treatment (degarelix, n = 565; goserelin, n = 283). The first endpoint (castrate from Days 3–364 vs. goserelin) was met; indeed, degarelix was statistically superior to goserelin (cumulative probability, 85% [81.6–87.8%] and 5.3% [3.1–8.4%], respectively). The second endpoint (castrate from Days 28–364) was not met as the lower bound of the 95% CI was below the predefined 90% threshold (cumulative probability, 90% [95% CI, 87.0–92.3%]). This reflects testosterone escape in some patients as a result of insufficient trough plasma degarelix levels at the end of the 3-month dosing period. Compared with goserelin, degarelix was not associated with initial testosterone surge and microsurges; it demonstrated a significantly faster PSA suppression and lower urinary tract symptom relief (in locally advanced disease) as well as lower incidence of arthralgia; and a significantly lower

risk of disease progression (in those with high baseline PSA; i.e. >50 ng/ml) (Table 1). Overall incidences of adverse events (AEs) were similar for degarelix vs. goserelin (75% vs. 71%). Injection site reactions were more common with degarelix (39% vs. 2%), while renal/urinary (9% vs. 17%) and musculoskeletal AEs (14% vs. 20%) were more common with goserelin. Table 1. Degarelix vs. goserelin ± bicalutamide in PCa

Testosterone Median level, Day 3 (ng/mL) PSA Median % reduction, Day 28 Probability of PSA failure, % Overall population Baseline PSA >50 ng/mL Disease progressiona Probability of disease progression, % Overall population Baseline PSA >50 ng/mL Symptom control Change in IPSS, Day 28 Overall population Locally advanced PCa Arthralgiab Change at Day 28 Overall population Metastatic disease

Degarelix (n = 565)

Goserelin ± bicalutamide (n = 283)

0.27

6.9

84†

66

13.5 34.9

13.5 45.0

21.0 42.2*

22.7 59.2

−0.99 −1.44*

−0.20 0.22

−3.76 −11.2*

−3.16 −5.94

*p < 0.05; † p < 0.0001 vs. goserelin. a PSA failure, death or additional PCa therapy. b Visual analogue scale. IPSS, International Prostate Symptom Score.

Conclusions: Treatment with 3-monthly degarelix was associated with a number of clinical benefits vs. goserelin in patients with PCa. These benefits are consistent with the results obtained in previous studies with once-monthly degarelix and confirm its role as a first-line androgen-deprivation therapy in PCa. P110 Efficacy and tolerability of 3- and 6-month depot formulations of leuprorelin acetate for advanced prostate cancer in daily clinical practice: Pooled data from 2 non-interventional studies C.H. Ohlmann1 , M. Gross-Langenhoff2 , U.W. Tunn3 . 1 Saarland University, Dept. of Urology, Homburg/Saar, Germany; 2 Astellas Pharma GmbH, Medical Department, Munich, Germany; 3 Urological Clinic Facharztzentrum Klinikum Offenbach, Urological Department, Offenbach/Main, Germany Introduction & Objectives: Androgen-deprivation therapy is the current standard therapy for advanced prostate cancer (PCa). This therapy often consists of injections of luteinising-hormone-releasing-hormone (LHRH) agonists. The LHRH agonist leuprorelin acetate (LA) is available in several formulations, including 1-, 3- and 6-month biodegradable polymer matrix depot formulations (Eligard® ), which have been shown to reduce testosterone and PSA levels in several clinical trials (Crawford ED et al. J Urol 2006;175:533–6/PerezMarrero R et al. Clin Ther 2002;24:1902–14/Chu FM et al. J Urol 2002;168:1199–203). The current study aimed at monitoring efficacy and tolerability of these formulations in PCa patients seen in daily clinical practice. Material & Methods: Two prospective, open-label, noninterventional studies were conducted in Germany. 1,906 advanced PCa patients starting treatment with either the 3-month (22.5 mg) or the 6-month (45 mg) LA depot formulation (Eligard® ) were followed during 12 months by 662 office-based urologists. Primary efficacy parameters total serum testosterone and PSA were measured at baseline and every 3 (for