PURPOSE: To determine the long-term outcomes for prostate adenocarcinoma when escalating radiation dose from 70 Gy to 78 Gy. METHODS AND MATERIALS: Between 1993 and 1998, 301 patients with biopsy-proven clinical stage T1b-T3 prostate adenocarcinoma, any prostate-specific antigen level, and any Gleason score were randomized to 70 Gy in 35 fractions versus 78 Gy in 39 fractions of photon radiation therapy using a 4-field box technique without hormone deprivation therapy. The primary outcome was powered to detect a 15% difference in biochemical or clinical failure. Secondary outcomes included survival, prostate cancer mortality, biochemical failure, local failure, nodal failure, distant failure, and secondary malignancy rates. RESULTS: With a median follow-up of 14.3 years, the cumulative incidence of 15-year biochemical or clinical failure was 18.9% versus 12.0% in the 70 Gy versus 78 Gy arms, respectively (subhazard ratio [sHR], 0.61; 95% confidence interval [CI], 0.38-0.98; Fine-Gray P = .042). The 15-year cumulative incidence of distant metastasis was 3.4% versus 1.1%, respectively (sHR, 0.33; 95% CI, 0.13-0.82; Fine-Gray P = .018). The 15-year cumulative incidence of prostate cancer-specific mortality was 6.2% versus 3.2%, respectively, (sHR, 0.52; 95% CI, 0.27-0.98; Fine-Gray P = .045). There were no differences in overall survival (HR, 1.10; 95% CI, 0.84-1.45; log rank P = .469) or other-cause survival (sHR, 1.33; 95% CI, 0.99-1.79; Fine-Gray P = .061). Salvage therapy was more common in the 70 Gy arm, at 38.7% versus 21.9% in the 78 Gy arm (P = .002). There was a 2.3% secondary solid malignancy rate (1 bladder, 6 rectal) within the radiation treatment field, which was not significantly different between treatment arms. CONCLUSIONS: Dose escalation by 8 Gy (78 Gy vs 70 Gy) provided a sustained improvement in biochemical and clinical failure, which translated into lower salvage rates and improved prostate cancer-specific mortality, but not overall survival. Long-term follow-up demonstrated a low incidence of potential solid tumor secondary malignancies.
RCT Entities:
PURPOSE: To determine the long-term outcomes for prostate adenocarcinoma when escalating radiation dose from 70 Gy to 78 Gy. METHODS AND MATERIALS: Between 1993 and 1998, 301 patients with biopsy-proven clinical stage T1b-T3 prostate adenocarcinoma, any prostate-specific antigen level, and any Gleason score were randomized to 70 Gy in 35 fractions versus 78 Gy in 39 fractions of photon radiation therapy using a 4-field box technique without hormone deprivation therapy. The primary outcome was powered to detect a 15% difference in biochemical or clinical failure. Secondary outcomes included survival, prostate cancer mortality, biochemical failure, local failure, nodal failure, distant failure, and secondary malignancy rates. RESULTS: With a median follow-up of 14.3 years, the cumulative incidence of 15-year biochemical or clinical failure was 18.9% versus 12.0% in the 70 Gy versus 78 Gy arms, respectively (subhazard ratio [sHR], 0.61; 95% confidence interval [CI], 0.38-0.98; Fine-Gray P = .042). The 15-year cumulative incidence of distant metastasis was 3.4% versus 1.1%, respectively (sHR, 0.33; 95% CI, 0.13-0.82; Fine-Gray P = .018). The 15-year cumulative incidence of prostate cancer-specific mortality was 6.2% versus 3.2%, respectively, (sHR, 0.52; 95% CI, 0.27-0.98; Fine-Gray P = .045). There were no differences in overall survival (HR, 1.10; 95% CI, 0.84-1.45; log rank P = .469) or other-cause survival (sHR, 1.33; 95% CI, 0.99-1.79; Fine-Gray P = .061). Salvage therapy was more common in the 70 Gy arm, at 38.7% versus 21.9% in the 78 Gy arm (P = .002). There was a 2.3% secondary solid malignancy rate (1 bladder, 6 rectal) within the radiation treatment field, which was not significantly different between treatment arms. CONCLUSIONS: Dose escalation by 8 Gy (78 Gy vs 70 Gy) provided a sustained improvement in biochemical and clinical failure, which translated into lower salvage rates and improved prostate cancer-specific mortality, but not overall survival. Long-term follow-up demonstrated a low incidence of potential solid tumor secondary malignancies.
Authors: Freddie C Hamdy; Jenny L Donovan; J Athene Lane; Malcolm Mason; Chris Metcalfe; Peter Holding; Michael Davis; Tim J Peters; Emma L Turner; Richard M Martin; Jon Oxley; Mary Robinson; John Staffurth; Eleanor Walsh; Prasad Bollina; James Catto; Andrew Doble; Alan Doherty; David Gillatt; Roger Kockelbergh; Howard Kynaston; Alan Paul; Philip Powell; Stephen Prescott; Derek J Rosario; Edward Rowe; David E Neal Journal: N Engl J Med Date: 2016-09-14 Impact factor: 91.245
Authors: David P Dearnaley; Gordana Jovic; Isabel Syndikus; Vincent Khoo; Richard A Cowan; John D Graham; Edwin G Aird; David Bottomley; Robert A Huddart; Chakiath C Jose; John H L Matthews; Jeremy L Millar; Claire Murphy; J Martin Russell; Christopher D Scrase; Mahesh K B Parmar; Matthew R Sydes Journal: Lancet Oncol Date: 2014-02-26 Impact factor: 41.316
Authors: Jianqing Lin; Robert B Den; Jacob Greenspan; Timothy N Showalter; Jean H Hoffman-Censits; Costas D Lallas; Edouard J Trabulsi; Leonard G Gomella; Mark D Hurwitz; Benjamin Leiby; Adam P Dicker; W Kevin Kelly Journal: Int J Radiat Oncol Biol Phys Date: 2020-02-03 Impact factor: 7.038
Authors: William A Hall; Snehal Deshmukh; Deborah W Bruner; Jeff M Michalski; James A Purdy; Walter Bosch; Jean-Paul Bahary; Maltibehn P Patel; Matthew B Parliament; Michael I Lock; Harold Y Lau; Luis Souhami; Scot A Fisher; Young Kwok; Michael J Seider; Eric Vigneault; Seth A Rosenthal; Gary S Gustafson; Hiram A Gay; Stephanie L Pugh; Howard M Sandler; Benjamin Movsas Journal: Int J Radiat Oncol Biol Phys Date: 2022-01-01 Impact factor: 7.038
Authors: Juanita Crook; Joseph P Rodgers; Thomas M Pisansky; Edouard J Trabulsi; Mahul B Amin; William Bice; Gerard Morton; Albert D Murtha; Eric Vigneault; Joelle Helou; Jeff M Michalski; Mack Roach; David Beyer; Ashesh B Jani; Eric M Horwitz; Adam Raben; Stephanie Pugh; Howard Sandler Journal: Int J Radiat Oncol Biol Phys Date: 2021-11-03 Impact factor: 7.038
Authors: Katharina Beyer; Vera Straten; Sebastiaan Remmers; Steven MacLennan; Sara MacLennan; Giorgio Gandaglia; Peter-Paul M Willemse; Ronald Herrera; Muhammad Imran Omar; Beth Russell; Johannes Huber; Markus Kreuz; Alex Asiimwe; Tom Abbott; Alberto Briganti; Mieke Van Hemelrijck; Monique J Roobol Journal: J Pers Med Date: 2022-05-05
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