The 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO-GU 2023) kicked off on February 16th in San Francisco, USA. In the field of prostate cancer radiation therapy, two phase 3 clinical studies were selected for oral presentation: The PACE-A study explores stereotactic body radiation therapy (SBRT) compared to surgery for localized prostate cancer; The CHHiP study further reports survival and comorbidity outcomes with a 12-year follow-up.
PACE-A: An International Phase 3 Randomized Controlled Trial (RCT) Comparing Stereotactic Body Radiation Therapy (SBRT) to Surgery for Localized Prostate Cancer (LPCa) – Primary Endpoint Analysis
Patients with LPCa can undergo radiation or surgery, but there is a lack of head-to-head research comparing the two. The PACE study (NCT01584258) is a Phase 3 open-label, multi-cohort RCT. In the PACE-A cohort, patients with resectable LPCa (T1-T2, Gleason ≤3+4, PSA ≤20ng/mL) were randomized (1:1) to the SBRT group (36.25Gy/5 times) or the surgery group (laparoscopic or robot-assisted radical surgery). None of the patients underwent androgen deprivation therapy (ADT). The study’s primary endpoint was patient-reported outcomes (PROs), assessed by the Expanded Prostate Cancer Index Composite-26 (EPIC-26) for 2-year incontinence and bowel symptoms.
The study enrolled a total of 123 patients, with a median age of 66 years, a median PSA of 8ng/ml, 52% of tumors ≥T2b, 79% being Gleason 3+4, and 93% of patients were white. 58/63 patients in the SBRT group and 48/60 in the surgery group received treatment. With a median follow-up of 50 months, the incontinence rate in the SBRT group was significantly lower than that in the surgery group, at 4.5% (2/43) and 46.9% (15/32) respectively (P<0.001). However, the bowel symptom scores in the SBRT group were worse compared to the surgery group (88.4 vs 97.3, P<0.001); the proportion of moderate/severe bowel symptoms reported in the SBRT group was also significantly higher (15.6% vs 0%; P=0.04). Additionally, the sexual function scores were higher in the SBRT group (58.0 vs 29.3, P<0.001). Urination symptom scores were similar between the two groups (85.5 vs 80.5, P=0.29).
At the 2-year mark, there was no significant difference between the two groups in the observed Grade ≥2 genitourinary adverse events (Common Terminology Criteria for Adverse Events, CTCAE GU) (9.3% vs 9.5%, P=0.97). Neither group experienced Grade ≥2 gastrointestinal adverse events.
Summary:
PACE-A provides the first randomized study data comparing SBRT to surgical treatment for LPCa. In comparisons with PROs as the primary endpoint, it’s evident that SBRT offers better urinary control and sexual function. Overall, gastrointestinal toxicity is lower, but gastrointestinal symptoms in SBRT patients are worse than in those who underwent surgery.
Prostate Cancer Conventional Radiation vs Large Fraction High Dose Intensity Modulated Radiation: A 10-year Efficacy and Comorbidity Outcome of a Phase III Randomized Trial (CHHiP; CRUK/06/016)
Large fraction radiation can reduce the number of radiation sessions, improving patient quality of life while ensuring efficacy. CHHiP is a randomized, Phase 3, non-inferiority trial that, from October 18, 2002, to June 17, 2011, enrolled 3,216 lymph node-negative, T1b-T3a stage prostate cancer patients with a risk of seminal vesicle involvement of ≤30%. They were randomized (1:1:1) to receive conventional radiation (74Gy/37f) or large fraction radiation (60Gy/20f group and 57Gy/19f group).
Results published in “The Lancet Oncology” in 2016 showed that the biochemical recurrence-free or clinical failure (BCF) survival rate of patients in the 60Gy/20f group was not inferior to those in the 74Gy/37f group (88.3% vs 90.6%; HR 0.84, 90%CI: 0.68~1.03, P=0.0018).
For patient groups that still have a risk of recurrence years after treatment, reporting long-term efficacy and side effects is crucial. This year’s ASCO-GU conference reported the 10-year efficacy and comorbidity outcomes of this study.
With a median follow-up time of 12.1 years, the 10-year BCF-free survival rates for patients in the 74Gy, 60Gy, and 57Gy groups were 76.0% (95%CI: 73.1%~78.6%), 79.8% (77.1%~82.3%), and 73.4% (70.5%~76.1%), respectively. Consistent with the initial analysis, the 60Gy group was not inferior to the 74Gy group (HR 0.84, 90%CI: 0.72~0.97), while the 57Gy group did not achieve non-inferiority (HR 1.13, 90%CI: 0.98~1.30).
The 10-year overall survival (OS) rates for the 74Gy, 60Gy, and 57Gy groups were 78.5% (95%CI: 75.9%~81.0%), 82.9% (80.4%~85.0%), and 79.9% (77.3%~82.2%), respectively.
At the 10-year follow-up, 2% (15/700) of patients in the 74Gy group, 2% (19/771) in the 60Gy group, and 3% (22/719) in the 57Gy group reported bone fracture events. The most commonly reported intervention for adverse events was sigmoidoscopy, with incidence rates in the three groups being 12% (79/681), 8% (60/739), and 9% (65/702) respectively. Among these, 81% (63/78) in the 74Gy group, 81% (48/59) in the 60Gy group, and 85% (55/65) in the 57Gy group underwent sigmoidoscopy due to gastrointestinal symptoms. Other pre-specified comorbidities or related interventions (ureteral obstruction, intestinal stricture, transurethral prostatectomy, urethrotomy, urethral dilation or long-term catheterization, or use of corticosteroids, sucralfate, formalin, laser coagulation, or rectal bypass for rectal disease) mostly occurred in <1% of patients in each group.
Summary: With a median follow-up time of 12 years, the oncological outcomes of the 60Gy/20f group continue to be non-inferior to the 74Gy/37f group. The incidence of late-onset comorbidities is very low in all treatment groups. These data suggest that moderate hypofractionated radiotherapy has good long-term safety.
References:
1. PACE-A: An international phase 3 randomised controlled trial (RCT) comparing stereotactic body radiotherapy (SBRT) to surgery for localized prostate cancer (LPCa) – Primary endpoint analysis. ASCO-GU 203; Abstract: 298.
2. 10-Year efficacy and co-morbidity outcomes of a phase III randomised trial of conventional vs. hypofractionated high dose intensity modulated radiotherapy for prostate cancer (CHHiP; CRUK/06/016). ASCO-GU 203; Abstract: 304.
3. Dearnaley D, Syndikus I, Mossop H, et al. Conventional versus hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial [published correction appears in Lancet Oncol. 2016 Aug; 17(8):e321]. Lancet Oncol. 2016; 17(8): 1047-1060. doi:10.1016/S1470-2045(16)30102-4.
