Update From the ASCO 2015 Genitourinary Cancers Symposium

Aaron Falchook, MD

At this year’s American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium in Orlando, Florida, several high-impact and potentially practice-changing abstracts were presented during the prostate cancer oral abstract session.

The ASCENDE-RT trial is a phase III randomized trial that evaluated high-dose radiotherapy with external beam boost vs brachytherapy boost for prostate cancer. All patients had intermediate- or high-risk prostate cancer as defined by the National Comprehensive Cancer Network (NCCN) and were treated with 12 months of androgen deprivation therapy (ADT), along with 46-Gy pelvic external beam radiotherapy (EBRT) to the prostate, seminal vesicles, and regional lymph nodes. The patients were randomized to receive either dose escalation via an EBRT boost of 32 Gy to the prostate (total dose, 78 Gy) or a brachytherapy boost with low-dose rate interstitial brachytherapy (115 Gy). The primary endpoint was biochemical progression-free survival (bPFS). The trial demonstrated a benefit at 7 years, with a bPFS of 86% in the brachytherapy arm vs 75% in the EBRT arm. There were no differences in metastasis-free survival, overall survival, or prostate cancer–specific survival. The cumulative incidence of grade 3 genitourinary toxicity was higher in the brachytherapy arm (19% vs 5%; P < .001), although at 5-year follow-up the difference was smaller (8.6% vs 2.2%). Gastrointestinal toxicity was relatively low in both arms (< 10%). This study showed an impressive bPFS for patients who received brachytherapy boost, compared with higher-risk patients from other dose-escalation trials. Furthermore, this trial gave us additional insight into the value of dose escalation in the setting of ADT use. Although published results in manuscript form are pending, findings from this trial may be practice-changing given the demonstrable benefit of a brachytherapy boost vs an EBRT boost.

Long-term results were presented from the RTOG 0126 trial, which randomized men with intermediate-risk prostate cancer to standard-dose radiotherapy (70.2 Gy) vs dose-escalated radiotherapy (79.2 Gy), with EBRT utilized in both treatment arms. ADT was not given in this study. Previously published results from this study and multiple other dose-escalation studies have shown improved bPFS for men who received dose-escalated radiotherapy. However, the long-term results presented at this year’s meeting were the first to show a statistically significant benefit with dose escalation in the reduction of distant metastasis (5% vs 8% at 10 years; P = .026). Furthermore, the use of salvage therapy was significantly lower among the dose-escalated group of patients (receipt of any salvage therapy was 13.5% for dose escalation vs 20.6% for standard dose; P = .0002). Differences in local progression and overall survival were not statistically significant. These results were significant in that they demonstrated that dose escalation alone (without ADT or any other systemic treatment) reduces the rate of prostate cancer distant metastases.

The final abstract that stood out is the Prostate Cancer Study III trial. This was a three-arm randomized trial of intermediate-risk prostate cancer patients that examined the following regimens: 1) short-term ADT plus prostate EBRT at 70 Gy, 2) short-term ADT plus prostate EBRT at 76 Gy, and 3) prostate EBRT alone at 76 Gy. The benefit of dose escalation in patients receiving ADT has not previously been well-studied. This current trial represents an important effort to fill that knowledge gap. With a median follow-up of 75 months, the addition of ADT improved biochemical control regardless of EBRT dose used. The difference in biochemical failure was not statistically significant between standard-dose and high-dose EBRT for men who received ADT (12.5% vs 8.0%; P = .187). Biochemical failure for dose-escalated EBRT without ADT was 21.5%. Rates of metastatic disease were lower among men who received ADT (1.5% for both ADT arms vs 5.5% for dose escalation alone). However, there were no differences in prostate cancer death or overall survival between arms, and the rate of cardiovascular death was higher in the ADT arms (11 patients each in the two ADT arms vs 5 patients in the EBRT-alone arm). These results suggested that from an oncologic outcomes perspective, the addition of ADT provides greater benefit than dose escalation, although the best outcomes were seen among men who received both ADT and dose escalation. Additional studies and longer follow-up are needed to better understand the role of ADT in the era of dose-escalated EBRT for prostate cancer. Baseline patient comorbidities, disease risk features, and patient preferences will ultimately play an important role in the optimal treatment selection for men with clinically localized prostate cancer.