Sequencing of Androgen-Deprivation Therapy With External-Beam Radiotherapy in Localized Prostate Cancer

[Balsam01]

TAKE-HOME MESSAGE

•The authors of this randomized phase III trial evaluated the optimal sequencing of androgen-deprivation therapy and dose-escalated radiotherapy in 432 patients with newly diagnosed localized prostate cancer. No statistically significant differences were seen in survival outcomes and late radiotherapy–related toxicities between those given neoadjuvant therapy and those given concurrent therapy.

•The authors concluded that either neoadjuvant or concurrent initiations of short-term androgen-deprivation therapy with dose-escalated radiation therapy are reasonable approaches in this clinical scenario.

– Paul J. Hampel, MD

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.

Journal of Clinical Oncology

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

J. Clin. Oncol 2019 Dec 12;[EPub Ahead of Print], S Malone, S Roy, L Eapen, C E, R MacRae, G Perry, J Bowen, R Samant, S Morgan, J Craig, K Malone, S Grimes

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

[timotur]

I read a study that indicated ADT sensitizes PCa to radiation, and another study that indicated chances for BCR are lower if PSA <0.6 going into external radiation. I did two months ADT before HDR-BT and lowered my PSA from 33 to 1.0 before the procedure, then one month later, PSA was 0.1 going into IMRT. Now five months later it is <0.01. So I favor the neo-adjunctive ADT route based on what I've read and experienced.

[tango65]

Link to the full article:

sci-hub.tw/https://ascopubs...

[tallguy2]

Thanks for posting this article.