ASTRO 2022: Postoperative iSRT plus degarelix improves MFS in prostate cancer with elevated PSA

Patients with prostate cancer who experience elevated levels of prostate-specific antigens after radical prostatectomy appear to benefit from
short-term androgen deprivation therapy following immediate salvage radiotherapy.

In prostate cancer patients with persistently high prostate-specific antigen (PSA) levels after radical prostatectomy (RP), short-term treatment with androgen deprivation therapy (ADT) with the androgen deprivation therapy (ADT) agent Firmagon improves metastasis-free survival (MFS), the results of this Phase 2 GETUG-AFU 22 trial were presented at the 2022 American Society of Radiation Oncology (ASTRO) Annual Meeting
。

The GETUG-AFU 22 study is a multicenter, randomized study
.
A total of 125 patients participated in the study
between December 2012 and September 2015.
These patients have post-RP PSA levels between 0.
2 and 2 ng/mL and no clinical signs
of disease progression.
Between December 2012 and September 2015, a total of 125 patients participated in the trial
.

Patients were randomized to iSRT+ ADT (Degarelix; 61 patients) or iSRT alone (64 patients).

iSRT consists of 46 Gy of pelvic radiation therapy in 23 doses of 2 Gy and up to 66 Gy (33 sessions) of prostate bed enhancement
.
Patients randomized to the experimental group received the same course of iSRT plus 6 months of concomitant degarelix at an initial dose of 240 mg, followed by a maintenance dose
of 80 mg five times per month.

The primary endpoint of the study was event-free survival (EFS), with secondary endpoints including 5-year event-free survival (EFS) and metastasis-free survival (MFS), 5- and 10-year overall survival, acute and late toxicities associated with study treatment, acute and late toxicities associated with radiotherapy modality, and quality of life (QOL).

The median follow-up was 74.
94 months
.

Overall, the characteristics of patients in both groups were well
balanced.
Of all 125 patients, the median age was 66 years (range 50-77 years).

The median Gleason score is 7 (on a scale of 3-9).

ECOG performance status was 0 in 114 patients, 1 in 10 patients, and missing in 1 patient
.
The median postoperative PSA before iSRT was 0.
6 ng/mL (range, 0.
12-3.
65).

Residual tumors are classified as R0 (32.
8%), R1 (65.
6%), and Rx (1.
6%)
.
The pT phases are T1 (0.
8%), T2 (36%), and T3 (63.
2%)
.
The pN phases are N0 (82.
4%) and Nx (17.
6%)
.

Latorzeff did note that there were more patients with tumor margin-negative (R0) in the ADT group compared to the iSRT group alone, at 24 and 17
, respectively.

At 5 years, no group reached the median EFS
.
EFS rates ranged from 62.
3% (95% CI, 48.
9 to 73.
2) in the control group compared to 63.
4% (95% CI, 49.
9 to 74.
2) in the iSRT plus ADT group (HR, 0.
83; 95% CI, 0.
47 to 1.
47; P = .
528).

The 5-year MFS rate for iSRT plus ADT was 91.
44% (95% CI, 80.
64-96.
35) compared to 78.
59% (95% CI, 65.
99-86.
97) for iSRT alone (HR, 0.
51; 95% CI, 0.
26-0.
99; P = .
048).

In addition, patients treated with iSRT and ADT had a 49%
lower risk of metastasis or death compared to the iSRT-only cohort.

"MFS, as a predictive marker for survival, tends to add short-term ADT plus iSRT to this population compared to iSRT alone," said
lead study author Igor Latorzeff of Groupe Oncorad Garonne in Toulouse, France.

Although there was no statistically significant difference in event-free survival (EFS) between the 2 groups, Latorzeff stated that out of 53 EFS events, "the probability that iSRT plus ADT was actually better than iSRT alone in this population was 79%
.
" ”

Explaining the background to the study, Latorzeff said, "Overall, 5% to 20% of patients undergoing radical prostatectomy develop a postoperative PSA of >0.
1 ng/ml within 6 to 8 weeks
postoperatively.
Persistence of PSA is a high-risk factor
for biochemical recurrence, metastatic disease, and cancer-specific death.
”

The researchers evaluated the second cancer and reported that there were three cases of the second cancer in the control group (bladder, mouth, and lung) and six in the combined group (multiple myeloma, lung cancer, glioma, bladder cancer, and 2 colorectal cancers),
Latorzeff said.
He noted that the second cancer has nothing to do with
the effectiveness of the treatment.

There was 1 death in the iSRT group alone (severe infection) and 5 deaths (dementia, multiple myeloma, colorectal cancer, glioma, polyarteritis nodosa)
in the iSRT plus ADT group.
According to Latorzeff, none of these deaths were related
to prostate cancer.

Latorzeff concluded by saying that the ongoing trials are intended to confirm the researchers' hypothesis that adding ADT to iSRT improves outcomes in this population, including the Phase 2 STEELE, Formula-509 and BALANCE trials, and the Phase 2/3 NRG-GU002 trial
.

Resources:

Latorzeff I, Guerif S, Castan F, et al.
GETUG-AFU 22: Phase II Randomized Trial Evaluating Outcomes of Post-Operative Immediate Salvage Radiation Therapy with or without ADT for Patients with Persistently Elevated PSA Level.
Presented at 2022 American Society for Radiation Oncology Annual Meeting (ASTRO); October 23-26, 2022; San Antonio, TX.
LBA 10.