(UroToday.com) The 2024 American Society for Radiation Oncology (ASTRO) annual meeting held in Washington D.C., between September 29 and October 2 was host to the session EDU 16 - Management of Unfavorable Intermediate-Risk Prostate Cancer: Role of SBRT, Brachytherapy and Androgen Deprivation Therapy. Dr. Jason Efstathiou presented the Prostate Advanced Radiation Technologies Investigating Quality of Life (PARTIQoL): Phase III Randomized Clinical Trial of Proton Therapy vs IMRT for Localized Prostate Cancer
Dr. Efstathiou began his presentation by highlighting the various management options available for patients with localized prostate cancer, which include external beam radiation therapy (EBRT) using either photons or protons. Proton beam therapy (PBT) offers unique physical and biological properties, enabling the delivery of highly conformal dose distributions when compared to conventional photon EBRT. This modality provides significant dosimetric advantages, with the potential to minimize morbidity by sparing healthy tissues and improving oncological outcomes. However, PBT facilities are more resource-intensive to establish and maintain than intensity-modulated radiation therapy (IMRT) facilities, requiring substantial infrastructure and resulting in lower patient throughput.
To investigate the hypothesis that PBT leads to enhanced patient-reported outcomes (PROs), the PARTIQoL trial (NCT01617161) a multi-center phase 3 randomized study compared the two radiation therapy modalities (PBT vs. IMRT).
The study inclusion criteria were:
- Males ≥ 18 years old
- Histologically confirmed adenocarcinoma of the prostate
- Clinical stage T1c-T2c
- Gleason score ≤ 7
- PSA <20 ng/mL
- ECOG-PS 0 or 1
Exclusion criteria were as follows:
- Nodal involvement (N1) or distant metastases (M1)
- Prior surgery for prostate cancer
- Prior treatment with pelvic RT or ADT
- Bilateral hip prostheses
- Inflammatory bowel disease
- Major medical illnesses
- Other malignancy within 5 years
Study stratification was based on study site, age (<65 years vs. ≥ 65 years), the use of a rectal spacer, and whether moderate hypofractionation was used. A total of 450 men were randomized to receive either PBT or IMRT, with the primary endpoint being bowel function at 24 months, assessed using the EPIC questionnaire. The study design diagram is shown below:
For the statistical analysis, 450 patients were required to be enrolled to provide 90% power with a two-sided 0.05-level t-test, accounting for 37% of unevaluable data at 24 months. Mean changes from baseline to 24 months in EPIC bowel, urinary, and sexual scores were compared using a t-test. Progression-free survival was analyzed using Cox proportional hazards models.
Dr. Efstathiou presented a timeline of major milestones for the study, beginning with the first activated site in June 2012 and the enrollment of the first patient in July 2012. The study successfully reached its goal of enrolling 450 patients by December 2019, with the last patient enrolled in November 2021. A total of 12 main proton centers and 29 recruiting centers collaborated on the study, fostering unity within the radiation community. The pragmatic trial design allowed investigators to incorporate changes in prostate cancer treatment (i.e. rectal spacers, hypofractionation) that inevitably occur over the course of a study. The details of this timeline are illustrated below:
Between July 2012 and November 2021, a total of 450 patients were accrued. The rate of patient enrollment varied over time, particularly following the publication of the ProtecT trial and during the COVID-19 pandemic. There was a notable decline in the number of low-risk prostate cancer patients enrolled, alongside an increase in the accrual of intermediate-risk prostate cancer patients.
.
A total of 515 patients were assessed for eligibility and 450 randomized of the randomized patients 226 received PBT and 224 IMRT, of whom 221 and 216 started RT on the respective arms. 167 and 162, respectively, informed the primary endpoint reflecting a 27% rate of missing data which was better than what was anticipated or planned for in the design (37%).
The baseline characteristics were well balanced as anticipated, the median follow-up was 60.3 months; 58% of patients in the PBT arm and 59% in the IMRT arm classified as having intermediate-risk prostate cancer, while 41% of patients in both arms were identified as having low-risk prostate cancer. The use of rectal spacers was similar across both groups, with 49% in the PBT arm compared to 47% in the IMRT arm. Details are presented in Table 1 below:
The primary endpoint of bowel function was assessed using the EPIC questionnaire, which ranges from 0 to 100. There was no significant difference in the mean change of the EPIC bowel score at 24 months between the PBT and IMRT groups (p=0.836), with both arms showing only a small, clinically insignificant decline from baseline. Furthermore, no differences in bowel function were observed at earlier time points (3, 6, 9, 12, and 18 months) or at later time points (36, 48, and 60 months).
Dr. Efstathiou noted that upon closer examination of the y-axis, there was a slight fluctuation in mean EPIC bowel scores between the PBT and IMRT groups; however, these fluctuations did not reach statistical significance at any time point. 
No differences were observed in the urinary domains at any timepoint, including urinary incontinence (p=0.99) and urinary irritation (p=0.85) as illustrated below:
There were some random fluctuations in the EPIC sexual domain mean change at 24 months (IMRT -6.0 vs. -10.6 PBT). However, curves are overlapping after 2 years (p=0.05).
In terms of disease control endpoints for the composite biochemical + clinical failure-free time endpoint (biochemical failure, local and non-local recurrence) the investigators tracked outcomes out to 5 years which was the median follow-up for these patients. The event-free survival at 60 months was 94.1% for IMRT compared to 96.7% for PBT; however, this difference was not statistically significant (p=0.31). It's important to note that the follow-up data remains immature, reflecting a very small number of events overall.
Similarly, there were no differences in terms of biochemical failure-free survival at 24 or 60 months (HR 1.14, p=0.71). 
The progression-free survival was 93.7% in the IMRT arm compared to 93.4% in the PBT arm at 60 months, the difference was not significant (p=0.71). The investigators examined cancer outcomes in 3 different ways and found no difference in cancer control out to 5 years in any. 
There was no sustained difference in any health-related quality of life (HRQoL) domain—specifically bowel, urinary, or sexual function—nor in cancer control between the PBT and IMRT arms when analyzed based on stratification factors such as age, fractionation schedule, and use of rectal spacers. This lack of significant differences persisted across key subgroups, including those categorized by intermediate versus low risk.
Dr. Efstathiou acknowledged several limitations of the trial, noting that the disease scope was restricted to localized low/intermediate risk prostate cancer. This study excluded patients with higher-risk disease, those undergoing nodal therapy, androgen deprivation therapy (ADT), or other systemic therapies, as well as local recurrences and retreatments. Furthermore, both PBT and IMRT technologies continue to evolve. Ongoing advancements in the field include improved imaging, adaptive delivery, and evolving practices such as ultrahypofractionation/SBRT, urethral sparing, and intraprostatic boosts, none of which were included in this trial.
To conclude the presentation Dr. Efstathiou delivered the following conclusions:
- Patients treated with contemporary radiotherapy for localized prostate cancer achieve excellent HRQoL alongside highly effective tumor control.
- In this Phase III randomized clinical trial comparing PBT and IMRT for patients with low and intermediate-risk prostate cancer, no significant differences were observed in HRQoL endpoints or cancer control outcomes between the two modalities.
- The investigators continue to monitor participants for longer-term follow-up and secondary endpoints. Additionally, they are analyzing results from a companion registry that includes participants who declined randomization or were denied insurance coverage.
Written by: Julian Chavarriaga, MD – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @chavarriagaj on Twitter during the 2024 American Society for Radiation Oncology (ASTRO) annual meeting held in Washington D.C., between the 29th of September and the 2nd of October.
Related content: Radiation Therapy Options for Localized Prostate Cancer Compared in Major Trial - Jason Efstathiou