A randomized trial of 79.2Gy versus 70.2Gy radiation therapy (RT) for localized prostate cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 4-4 ◽  
Author(s):  
Jeff M. Michalski ◽  
Jennifer Moughan ◽  
James Purdy ◽  
Walter Bosch ◽  
Jean-Paul Bahary ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dose Escalation ◽  
Late Toxicity ◽  
Phase Iii ◽  
Localized Prostate Cancer ◽  
Rank Test ◽  
High Dose ◽  
Local Progression ◽  
Gu Toxicity ◽  
Grade 3

4 Background: RTOG 0126 is a phase III trial for localized prostate cancer (PC) testing whether dose escalation to 79.2Gy with 3DCRT or IMRT will improve overall survival (OS). Methods: Stage cT1b-T2b with Gleason Score (GS) 2-6 and PSA ≥ 10 and <20 or GS 7 and PSA <15 were eligible and randomized to receive 79.2Gy or 70.2Gy. No androgen withdrawal was used. Treatment was 3DCRT or IMRT to 79.2Gy in 44 fractions or 70.2Gy in 39 fractions. The objective was to detect a 23% reduction in mortality hazard (HR=0.77) for 79.2Gy. ASTRO and Phoenix definition was used for biochemical failure (BF). Time to local progression (LP), distant metastases (DM), PC death, and late GI/GU toxicity was calculated from date of registration. OS was estimated by Kaplan Meier and arms compared with log rank test. BF, LP, DM, time to late GI/GU, and PC death were estimated by cumulative incidence method and arms compared with Gray’s test. Results: 1,532 men were randomized, 763 to 79.2Gy and 769 to 70.2Gy. 1,499 were eligible, 751 and 748 in the 79.2Gy and 70.2Gy arms respectively. Median age was 69, 70% had PSA < 10 ng/ml, 84% with GS 7, 57% had T1 disease, and 66% used 3D-CRT. With a median of 7.0 years follow up, the 5 and 10-yr rates of OS are 88% and 67% with 79.2Gy and 89% and 66% with 70.2Gy (p=0.87; HR (95%CI)=0.98 (0.79,1.21)). The ASTRO (Phoenix) BF rates at 5 and 10 yr are 25% (16%) and 30% (26%) with 79.2Gy and 40% (21%) and 45% (43%) with 70.2Gy (both p<0.0001). The 5 and 10-yr rates of LP are 1% and 4% with 79.2Gy and 2% and 8% with 70.2Gy (p=0.0059; HR (95%CI)=0.46 (0.27,0.81)). The 5 and 10 yr rates of DM are 2% and 5% with 79.2Gy and 3% and 8% with 70.2Gy (p=0.026; HR (95%CI)=0.57 (0.35,0.94)). The high dose arm had lower rate of salvage therapy, 13.5% vs 21%, p=0.0002. The 10 yr rates for time to late grade ≥ 2 GI/GU are 22%/15% with 79.2Gy and 16%/10% with 70.2Gy (p=0.0063/p=0.001). Time to late grade ≥ 3 GI was higher for the 79.2Gy arm (p=0.035) but time to late grade ≥ 3 GU toxicity was not (p=0.14). Conclusions: Despite significant improvement in BF, DM, and LP rates, dose escalation did not improve OS. Patients receiving high dose radiation experience more late toxicity. Clinical trial information: NCT00033631.

scholarly journals Sequencing of Androgen-Deprivation Therapy With External-Beam Radiotherapy in Localized Prostate Cancer: A Phase III Randomized Controlled Trial

2020 ◽  
Vol 38 (6) ◽  
pp. 593-601 ◽  
Author(s):  
Shawn Malone ◽  
Soumyajit Roy ◽  
Libni Eapen ◽  
Choan E ◽  
Robert MacRae ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Androgen Deprivation ◽  
Phase Iii ◽  
Localized Prostate Cancer ◽  
Definitive Treatment ◽  
Rank Test ◽  
Log Rank Test ◽  
Significant Difference ◽  
Grade 3

PURPOSE Dose-escalated radiotherapy (RT) with androgen-deprivation therapy (ADT) is a standard definitive treatment of localized prostate cancer (LPCa). The optimal sequencing of these therapies is unclear. Our phase III trial compared neoadjuvant versus concurrent initiation of ADT in combination with dose-escalated prostate RT (PRT). PATIENTS AND METHODS Patients with newly diagnosed LPCa with Gleason score ≤ 7, clinical stage T1b to T3a, and prostate-specific antigen < 30 ng/mL were randomly allocated to neoadjuvant and concurrent ADT for 6 months starting 4 months before RT (neoadjuvant group) or concurrent and adjuvant ADT for 6 months starting simultaneously with RT (concurrent group). The primary end point was biochemical relapse-free survival (bRFS). Stratified log-rank test was used to compare bRFS and overall survival (OS). Incidence of grade ≥ 3 late RT-related toxicities was compared by log-rank test. RESULTS Overall, 432 patients were randomly assigned to the neoadjuvant (n = 215) or concurrent group (n = 217). At 10 years, bRFS rates for the two groups were 80.5% and 87.4%, respectively. Ten-year OS rates were 76.4% and 73.7%, respectively. There was no significant difference in bRFS ( P = .10) or OS ( P = .70) between the two groups. Relative to the neoadjuvant group, the hazard ratio for the concurrent group was 0.66 (95% CI, 0.41 to 1.07) for bRFS and 0.94 (95% CI, 0.68 to 1.30) for OS. No significant difference was observed in the 3-year incidence of late RT-related grade ≥ 3 GI (2.5% v 3.9%) or genitourinary toxicity (2.9% v 2.9%). CONCLUSION In our study, there was no statistically significant difference in bRFS between the two treatment groups. Similarly, no difference was seen in OS or late RT-related toxicities. On the basis of these results, both neoadjuvant and concurrent initiations of short-term ADT with dose-escalated PRT are reasonable standards of care for LPCa.

Late toxicity and quality of life from GETUG-AFU 22 study.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 331-331
Author(s):  
Igor Latorzeff ◽  
Stephane Guerif ◽  
Sandra Pelissier ◽  
Emmanuel Meyer ◽  
Julien Fraisse ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Prostate Cancer ◽  
Late Toxicity ◽  
Localized Prostate Cancer ◽  
Efficacy Analysis ◽  
Prostate Bed ◽  
Gu Toxicity ◽  
Significant Difference ◽  
Grade 3

331 Background: Radical prostatectomy (RP) is recommended as a standard treatment for localized prostate cancer. However no recommendations exist for pts with immediate detectable PSA after RP. Methods: Pts with localized prostate cancer, treated by RP (R0 or R1), with a PSA level post-RP ≥0.2 ng/mL and ≤2 ng/mL at randomization and N0 M0 on imaging were included. Pts were randomized (1:1) to radiotherapy (RT) alone (RT arm) or 6 months degarelix hormone therapy (HT) with RT (RT+HT arm). RT consisted of pelvic irradiation (46 Gy in 23 Fr) with a boost on the prostate bed (66 Gy in 33 Fr). The primary endpoint was event-free survival (EFS). Acute and late toxicities were evaluated as secondary endpoints and scored using CTCAE V4.0 scale. Quality of life (QOL) was assessed with QLQ-C30 and QLQ-PR25 questionnaires at 12 and 24 months. Late toxicity was reported at 24 months. Results: From Jan-2013 to Sept-2015, 125 pts were included (RT arm: 64 pts; RT+HT arm: 61). Median follow up is 38 months (31.4; 44). The baseline characteristics are well-balanced between two arms: median age was 66 yrs (50-77), all men having an ECOG ≤1 (ECOG 0 in 92%), a median Gleason score of 7 (3-9), a median PSA of 0.3 ng/mL (0.09-1.82) post-RP and 0.6 ng/mL (0.12-3.65) at randomization. All pts received 33 Fr of RT. In the RT+HT arm 98.4% of pts received the 6 months of HT planned. All pts were eligible for safety analysis. At 24 months, no difference in late genitourinary (GU) or gastrointestinal (GI)toxicity was observed between the two arms (p=0.145) Grade 3 late toxicities were reported for 15/125 pts (12%): 8/64 pts (6.5%) in the RT arm and 7/61 pts (5.5%) in RT+HT arm (NS) and no toxicity grade >3 was observed. Evaluation of QOL was assessable at 12 and 24 months of FU for 80%/89% pts and 59%/77% pts in RT/RT-HT arms respectively. At 12 months QLQ-PR25 HT related symptoms was significantly more important in the RT-HT arm (p=0.04). At 24 months no significant difference in QLQC-30 or QLQ-PR25 analysis was reported. Conclusions:, At 24 months in this phase II trial no significant difference in GI/GU toxicity and.QOL was observed between the two arms. GETUG-AFU 22 efficacy analysis is still pending. Clinical trial information: NCT01994239.

scholarly journals Radiation therapy dose and androgen deprivation therapy in localized prostate cancer: a meta-regression of 5-year outcomes in phase III randomized controlled trials

2021 ◽  
Author(s):  
Tommy Jiang ◽  
Daniela Markovic ◽  
Jay Patel ◽  
Jesus E. Juarez ◽  
Ting Martin Ma ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiation Therapy ◽  
Androgen Deprivation Therapy ◽  
Dose Escalation ◽  
Low Dose ◽  
Androgen Deprivation ◽  
Phase Iii ◽  
Localized Prostate Cancer ◽  
Treatment Intensification ◽  
Meta Regression

Abstract Background While multiple randomized trials have evaluated the benefit of radiation therapy (RT) dose escalation and the use and prolongation of androgen deprivation therapy (ADT) in the treatment of prostate cancer, few studies have evaluated the relative benefit of either form of treatment intensification with each other. Many trials have included treatment strategies that incorporate either high or low dose RT, or short-term or long-term ADT (STADT or LTADT), in one or more trial arms. We sought to compare different forms of treatment intensification of RT in the context of localized prostate cancer. Methods Using preferred reporting items for systemic reviews and meta-analyses (PRISMA) guidelines, we collected over 40 phases III clinical trials comparing different forms of RT for localized prostate cancer. We performed a meta-regression of 40 individual trials with 21,429 total patients to allow a comparison of the rates and cumulative proportions of 5-year overall survival (OS), prostate cancer-specific mortality (PCSM), and distant metastasis (DM) for each treatment arm of every trial. Results Dose-escalation either in the absence or presence of STADT failed to significantly improve any 5-year outcome. In contrast, adding LTADT to low dose RT significantly improved 5-year PCSM (Odds ratio [OR] 0.34, 95% confidence interval [CI] 0.22–0.54, p < 0.001) and DM (OR 0.35, 95% CI 0.20–0.63. p < 0.001) over low dose RT alone. Adding STADT also significantly improved 5-year PCSM over low dose RT alone (OR 0.55, 95% CI 0.41–0.75, p < 0.001). Conclusion While limited by between-study heterogeneity and a lack of individual patient data, this meta-analysis suggests that adding ADT, versus increasing RT dose alone, offers a more consistent improvement in clinical endpoints.

scholarly journals Simulation of an HDR “Boost” with Stereotactic Proton versus Photon Therapy in Prostate Cancer: A Dosimetric Feasibility Study

2020 ◽  
Author(s):  
Jill S. Remick ◽  
Pouya Sabouri ◽  
Mingyao Zhu ◽  
Søren M. Bentzen ◽  
Kai Sun ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dose Escalation ◽  
Locally Advanced ◽  
High Dose Rate ◽  
Rank Test ◽  
High Dose ◽  
Prostate Brachytherapy ◽  
High Risk Prostate Cancer ◽  
Prostate Size ◽  
Ct Simulation

Abstract Purpose/Objectives To compare the dose escalation potential of stereotactic body proton therapy (SBPT) versus stereotactic body photon therapy (SBXT) using high-dose rate prostate brachytherapy (HDR-B) dose-prescription metrics. Patients and Methods Twenty-five patients previously treated with radiation for prostate cancer were identified and stratified by prostate size (≤ 50cc; n = 13, &gt; 50cc; n = 12). Initial CT simulation scans were re-planned using SBXT and SBPT modalities using a prescription dose of 19Gy in 2 fractions. Target coverage goals were designed to mimic the dose distributions of HDR-B and maximized to the upper limit constraint for the rectum and urethra. Dosimetric parameters between SBPT and SBXT were compared using the signed-rank test and again after stratification for prostate size (≤ 50cm3 and &gt;50cm3) using the Wilcoxon rank test. Results Prostate volume receiving 100% of the dose (V100) was significantly greater for SBXT (99%) versus SBPT (96%) (P ≤ 0.01), whereas the median V125 (82% vs. 73%, P &lt; 0.01) and V200 (12% vs. 2%, P &lt; 0.01) was significantly greater for SBPT compared to SBXT. Median V150 was 49% for both cohorts (P = 0.92). V125 and V200 were significantly correlated with prostate size. For prostates &gt; 50cm3, V200 was significantly greater with SBPT compared to SBXT (14.5% vs. 1%, P = 0.005), but not for prostates 50cm3 (9% vs 4%, P = 0.11). Median dose to 2cm3 of the bladder neck was significantly lower with SBPT versus SBXT (9.6 Gy vs. 14 Gy, P &lt; 0.01). Conclusion SBPT and SBXT can be used to simulate an HDR-B boost for locally advanced prostate cancer. SBPT demonstrated greater dose escalation potential than SBXT. These results are relevant for future trial design, particularly in patients with high risk prostate cancer who are not amenable to brachytherapy.

Long-term versus short-term androgen deprivation combined with high-dose radiotherapy for localized prostate cancer: A Spanish multicenter phase III trial.

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. e15036-e15036 ◽  
Author(s):  
A. Zapatero ◽  
A. Guerrero ◽  
X. Maldonado ◽  
A. Alvarez ◽  
C. González San Segundo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation ◽  
Phase Iii ◽  
Localized Prostate Cancer ◽  
High Dose ◽  
Short Term ◽  
Phase Iii Trial ◽  
Multicenter Phase

Comparison of hypofractionated high-dose intensity-modulated radiotherapy schedules for prostate cancer: Results from the phase III randomized CHHiP trial (CRUK/06/016).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 2-2 ◽  
Author(s):  
David P. Dearnaley ◽  
Isabel Syndikus ◽  
Helen Mossop ◽  
Alison J. Birtle ◽  
DJ Bloomfield ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Intensity Modulated Radiotherapy ◽  
Dose Intensity ◽  
Late Toxicity ◽  
Phase Iii ◽  
High Dose ◽  
Significant Difference ◽  
Patient Reported ◽  
Free Rate

2 Background: We aimed to explore the dose response relationship for two 3 Gray (Gy) hypofractionated radiotherapy (hRT) schedules for localised prostate cancer (PCa). Methods: hRT schedules of 60Gy/20 fractions (f) and 57Gy/19f were compared with conventional RT (cRT) 74Gy/37f; iso-effective for alpha-beta ratios of 2.5Gy and 1.5Gy respectively. The trial was powered to demonstrate non-inferiority between each hRT schedule and cRT, with 3,213 patients (pt) needed to rule out 5% inferiority (80% power, 1-sided alpha 5%) assuming 70% event-free rate in cRT, corresponding to a critical hazard ratio (HR) of 1.21. The trial was not formally powered to directly compare the two hRT schedules. Pt with N0 T1b-T3a localised PCa were randomized (1:1:1 ratio). The primary endpoint was PCa progression (freedom from biochemical failure by Phoenix consensus guidelines or PCa recurrence). Acute toxicity was assessed up to 18 weeks post treatment and late side effects to 5 years (yr) by RTOG, LENT-SOM and patient reported outcomes (PROs). Results: 3,216 pts were randomized between 2002 and 2011; 1,065 (74Gy), 1,074 (60Gy), 1,077 (57Gy). Baseline characteristics were well balanced across groups: median age 69 yr; NCCN risk group 15% low, 73% intermediate, 12% high. With median follow up 5.2yr, 5yr progression-free rate (95% CI) was 74Gy: 88.3% (86.0%, 90.2%); 60Gy: 90.6% (88.5%, 92.3%), 57Gy: 85.9 (83.4, 88.0); HR60/74: 0.83, 90% CI (0.68, 1.03), HR57/74: 1.20, 90% CI (0.99, 1.45). Significantly more events were observed with 57Gy compared to 60Gy; HR57/60: 1.44, 90% CI (1.18, 1.75), log-rank p=0.003. No significant difference in acute RTOG bladder or bowel toxicity was observed between hRT schedules. Late toxicity profile was favorable; with grade 2+ RTOG bladder (60Gy: 16/960 (1.7%); 57Gy: 11/962 (1.1%), p=0.34) and bowel (60Gy: 28/960 (2.9%); 57Gy: 17/962 (1.8%), p=0.10) toxicity at 2yr. Analysis of LENT-SOM and PROs supported these results. Conclusions: With 5 yr follow-up treatment with a 3Gy schedule of 60Gy/20f shows improved treatment efficacy compared to 57Gy/19f and is non-inferior to 74Gy/37f with a similar low level of acute and late normal tissue damage. Clinical trial information: ISRCTN97182923.

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