Trude B Wedde1, Milada C Småstuen2, Sigmund Brabrand3, Sophie D Fosså4, Stein Kaasa5, Gunnar Tafjord3, Kjell M Russnes6, Taran P Hellebust7, Wolfgang Lilleby3. 1. Department of Oncology, Oslo University Hospital and University of Oslo, Norway. Electronic address: t.b.wedde@studmed.uio.no. 2. Department of Health, Nutrition and Management, Oslo and Akershus University College of Applied Sciences, Norway. Electronic address: miladacv@medisin.uio.no. 3. Department of Oncology, Oslo University Hospital, Norway. 4. National Advisory Unit on Late Effects after Cancer Treatment, Oslo University Hospital, Norway. 5. Department of Oncology, Oslo University Hospital and University of Oslo, Norway. 6. Department of Oncology, Akershus University Hospital, Lørenskog, Norway. 7. Department of Medical Physics, Oslo University Hospital, Norway.
Abstract
BACKGROUND: The survival benefit of dose-escalation with High-Dose-Rate brachytherapy (HDR-BT) boost combined with External Beam Radiotherapy (EBRT) for the treatment of high-risk prostate cancer (PCa) remains debatable. We investigated 10-year PCa-specific mortality (PCSM) and overall mortality (OM) in high-risk patients treated with HDR-BT/EBRT (calculated EQD2 = 102 Gy) compared to EBRT alone (70 Gy). METHODS: HDR-BT boosts (10 Gy × 2) were given 2 weeks apart followed by 50 Gy conformal EBRT (2 Gy × 25) to the prostate and seminal vesicles. The HDR-BT/EBRT group (N:325) received Androgen Deprivation Therapy for a median duration of 2 years. The historical control group (N:296), received a median dose of 70 Gy (2 Gy × 35) to the prostate and seminal vesicles with lifelong Anti-Androgen Treatment. For each treatment group PCSM and OM were established by competing-risk analyses and Kaplan-Meier analyses respectively. Differences were evaluated by the logrank test. Independent associations were established by Cox regression analyses. Significance level set to p < 0.05. RESULTS: Median follow-up was 104 and 120 months for the HDR-BT/EBRT and the EBRT group respectively. A 3.6-fold decreased risk of PCSM (p < 0.01) and a 1.6-fold decreased risk of OM (p = 0.02) in the HDR-BT/EBRT cohort compared to the EBRT-only group were revealed. Ten-year OM and PCSM rates were 16% and 2.5% in the HDR-BT/EBRT group versus 23% and 8.2% in the EBRT-only group respectively. Both treatment modality (HR = 3.59, 95%CI 1.50-8.59) and Gleason score (HR = 2.48, 95%CI 1.18-5.21) were associated with PCSM. Only treatment modality (HR = 1.63, 95%CI = 1.08-2.44) was significantly associated with OM. CONCLUSIONS: Men with high-risk PCa have a significantly reduced PCSM and OM rates when treated with dose-escalated radiotherapy achieved by HDR-BT/EBRT compared to EBRT alone (70 Gy). A Gleason score of 8-10 was independently associated with increased risk of PCSM. Randomized studies are warranted. SUMMARY: Observational study of 10-year survival in high-risk Prostate Cancer (PCa) after High-Dose-Rate brachytherapy combined with External Beam Radiation Therapy (HDR-BT/EBRT) compared to EBRT alone. The combined HDR-BT/EBRT treatment was found to give a 3.6-fold decrease in Prostate Cancer Specific Mortality (PCSM) and a 1.6-fold decrease in Overall Mortality (OM). Gleason score and type of treatment strongly influenced PCSM whereas only treatment modality was associated with OM. The observed benefits of dose-escalation warrant future randomized trials.
BACKGROUND: The survival benefit of dose-escalation with High-Dose-Rate brachytherapy (HDR-BT) boost combined with External Beam Radiotherapy (EBRT) for the treatment of high-risk prostate cancer (PCa) remains debatable. We investigated 10-year PCa-specific mortality (PCSM) and overall mortality (OM) in high-risk patients treated with HDR-BT/EBRT (calculated EQD2 = 102 Gy) compared to EBRT alone (70 Gy). METHODS: HDR-BT boosts (10 Gy × 2) were given 2 weeks apart followed by 50 Gy conformal EBRT (2 Gy × 25) to the prostate and seminal vesicles. The HDR-BT/EBRT group (N:325) received Androgen Deprivation Therapy for a median duration of 2 years. The historical control group (N:296), received a median dose of 70 Gy (2 Gy × 35) to the prostate and seminal vesicles with lifelong Anti-Androgen Treatment. For each treatment group PCSM and OM were established by competing-risk analyses and Kaplan-Meier analyses respectively. Differences were evaluated by the logrank test. Independent associations were established by Cox regression analyses. Significance level set to p < 0.05. RESULTS: Median follow-up was 104 and 120 months for the HDR-BT/EBRT and the EBRT group respectively. A 3.6-fold decreased risk of PCSM (p < 0.01) and a 1.6-fold decreased risk of OM (p = 0.02) in the HDR-BT/EBRT cohort compared to the EBRT-only group were revealed. Ten-year OM and PCSM rates were 16% and 2.5% in the HDR-BT/EBRT group versus 23% and 8.2% in the EBRT-only group respectively. Both treatment modality (HR = 3.59, 95%CI 1.50-8.59) and Gleason score (HR = 2.48, 95%CI 1.18-5.21) were associated with PCSM. Only treatment modality (HR = 1.63, 95%CI = 1.08-2.44) was significantly associated with OM. CONCLUSIONS:Men with high-risk PCa have a significantly reduced PCSM and OM rates when treated with dose-escalated radiotherapy achieved by HDR-BT/EBRT compared to EBRT alone (70 Gy). A Gleason score of 8-10 was independently associated with increased risk of PCSM. Randomized studies are warranted. SUMMARY: Observational study of 10-year survival in high-risk Prostate Cancer (PCa) after High-Dose-Rate brachytherapy combined with External Beam Radiation Therapy (HDR-BT/EBRT) compared to EBRT alone. The combined HDR-BT/EBRT treatment was found to give a 3.6-fold decrease in Prostate Cancer Specific Mortality (PCSM) and a 1.6-fold decrease in Overall Mortality (OM). Gleason score and type of treatment strongly influenced PCSM whereas only treatment modality was associated with OM. The observed benefits of dose-escalation warrant future randomized trials.
Authors: Anna Rita Alitto; Luca Tagliaferri; Valentina Lancellotta; Andrea D'Aviero; Antonio Piras; Vincenzo Frascino; Francesco Catucci; Bruno Fionda; Christian Staackmann; Simonetta Saldi; Vincenzo Valentini; Gyorgy Kovacs; Cynthia Aristei; Giovanna Mantini Journal: In Vivo Date: 2020 May-Jun Impact factor: 2.155
Authors: Sophie D Fosså; Alv A Dahl; Tom Børge Johannesen; Ylva M Gjelsvik; Anne Holck Storås; Tor Å Myklebust Journal: Clin Transl Radiat Oncol Date: 2022-08-06
Authors: Andreas Pettersson; Daniel Alm; Hans Garmo; Marie Hjelm Eriksson; Enrique Castellanos; Lennart Åström; Jon Kindblom; Anders Widmark; Adalsteinn Gunnlaugsson; Ingela Franck Lissbrant; Per Nilsson; Pär Stattin Journal: JNCI Cancer Spectr Date: 2020-02-14
Authors: Amit Roy; Randall J Brenneman; Jacob Hogan; Justin M Barnes; Yi Huang; Robert Morris; Sreekrishna Goddu; Michael Altman; Jose Garcia-Ramirez; Harold Li; Jacqueline E Zoberi; Arnold Bullock; Eric Kim; Zachary Smith; Robert Figenshau; Gerald L Andriole; Brian C Baumann; Jeff M Michalski; Hiram A Gay Journal: Clin Transl Radiat Oncol Date: 2021-05-13