What Does NRG GU002 Mean for Docetaxel After Prostatectomy?

Patients with high-risk prostate cancer and a persistent prostate-specific antigen (PSA) level after radical prostatectomy have a substantial risk of recurrence despite postoperative radiotherapy. The phase 2/3 NRG GU002 trial (NCT03070886) evaluated whether adding 6 cycles of docetaxel after radiation and androgen deprivation therapy (ADT) could improve outcomes in this population.¹ The trial built on the single-arm NRG Oncology/RTOG 0621 study. Results were presented at the 2026 American Society for Radiation Oncology (ASTRO) Annual Meeting.²

At the meeting, CancerNetwork® spoke with study presenter Mark D. Hurwitz, MD, FASTRO, FACRO, who serves as chair of the Department of Radiation Medicine at New York Medical College and is the director of radiation medicine at Westchester Medical Center.

Hurwitz began by explaining what led to the trial’s early closure and describing the end points that demonstrated a benefit with docetaxel. He then discussed the finding that patients with lower genomic risk appeared to benefit most. He also explained why the results represent a signal rather than a definitive answer, and he concluded by highlighting the role of molecular subtyping as a key development in prostate cancer at this year’s meeting.

CancerNetwork: The trial closed early. What drove that decision?

Hurwitz: It was unfortunate that the trial closed early, and it was because of poor accrual over time. What we saw during the years the trial was open was that the realm of androgen receptor pathway inhibitor [ARPI] medications became broader. There was interest in that route of therapy, given a perceived more favorable toxicity profile than docetaxel. I think it was a combination of factors that unfortunately led to the premature cessation of the trial.

Which efficacy end points best demonstrate whether adding adjuvant docetaxel to radiation and ADT meaningfully reduces recurrence in patients with a persistent postoperative PSA or high-risk features?

The primary end point of the study, freedom from progression, was a positive finding in favor of docetaxel. That was a notable and important development for how we may think in the future about integrating chemotherapy into the treatment of high-risk patients after prostatectomy.

It was also notable that local-regional progression was significantly reduced with docetaxel. For patients not receiving docetaxel, it was 28.1%, and that was driven down to 11.0% with chemotherapy [P = 0.0046].

How are you evaluating outcomes across genomically defined subgroups, and do you anticipate that higher Decipher risk scores will ultimately identify a subset of patients who derive a true clinical benefit from adjuvant chemotherapy?

Genomic classification continues to be an evolving area. Both this trial and others are pointing to the utility of genomic classification in our higher-risk patients.

It was also a provocative finding that, within the overall high-risk population, it was the patients with low and intermediate genomic classifier risks who benefited in the trial. You would expect that it would be the patients with a high genomic classifier risk who benefit from chemotherapy. Perhaps there is something else going on in terms of the evolution and the biology, and we will have to see what future studies tell us in that regard.

Where do you see taxane-based chemotherapy fitting into the future postprostatectomy treatment landscape, and what questions remain about the optimal systemic doublet or triplet backbones to pair with radiotherapy?

Even with the favorable findings of the current study, we have to keep in mind that this was a phase 2/3 trial that was halted after 175 patients were enrolled, with 165 evaluable in the phase 2 component. What we have here, I believe, is a strong signal that there is a population of patients who will benefit from chemotherapy. But it is a question that remains to be definitively answered in future studies.

As for the optimal combination of agents, a number of questions remain. There are, of course, other chemotherapy drugs that could be considered, but the optimal combination is still an open question.

What has been the most significant advancement in radiation oncology for prostate cancer that you have observed this year?

Particularly, here at the meeting, we saw the presentation on the PAM50 signature, and the findings come as no surprise.³ We know that we have patients with luminal B prostate cancer, just as we have patients with luminal B breast cancer, and these are a subgroup of patients with a worse prognosis.

The questions that remain are how we best integrate not just prognostic but also predictive factors, as we are starting to see from a range of different approaches. It is going to be an interesting time to see which of the different options wins out. Or perhaps it is not about which one wins out, but about how treatment arms ultimately provide benefit, or differing benefit, to certain populations, particularly where we can predict outcomes with greater certainty.

References

1. Hurwitz MD, Harris J, Sartor O, et al. Adjuvant radiation therapy, androgen deprivation, and docetaxel for high-risk prostate cancer postprostatectomy: results of NRG Oncology/RTOG study 0621. Cancer. 2017;123(13):2489-2496. doi:10.1002/cncr.30620
2. Hurwitz MD, Johnson T, Sartor AO, et al. The role of docetaxel in addition to salvage radiation and androgen deprivation in men with high risk prostate cancer post-prostatectomy: results of NRG GU002. Presented at: 2026 ASTRO Annual Meeting; September 26-30, 2026; Boston, MA. Abstract 250.
3. Tran PT, Johnson M, Proudfoot J, et al. Evaluation of PAM50 molecular subtypes in post-prostatectomy salvage radiotherapy: an NRG Oncology-RTOG 0534 analysis. Presented at: 2026 ASTRO Annual Meeting; September 26-30, 2026; Boston, MA. Abstract 6.