In May 2026, Johnson & Johnson announced positive final results from the Phase III PROTEUS trial, demonstrating that apalutamide plus ADT significantly improved both short- and long-term clinical outcomes compared with placebo plus ADT. Patients receiving the combination were approximately nine times more likely to achieve pathologic complete response or minimal residual disease at surgery (8.9% vs. 1.0%), while the regimen reduced the risk of metastasis or death by 20%.

The study enrolled 2,109 patients with newly diagnosed high-risk localized or locally advanced prostate cancer, randomized to receive either apalutamide plus ADT or placebo plus ADT before and after radical prostatectomy. With a median follow-up of 61.7 months, the trial met both primary endpoints. The 5-year metastasis-free survival rate reached 78.2% in the apalutamide arm compared with 73.5% in the control arm, while additional secondary endpoints including event-free survival, time to distant metastasis, and time to first subsequent therapy were also significantly improved. These findings support the potential role of perioperative apalutamide in redefining treatment paradigms for patients with high-risk localized and locally advanced prostate cancer.

KOL insights

“Reducing the risk of prostate cancer recurrence and death with improved initial treatment regimens has been a longstanding unmet need for patients with localized high-risk prostate cancer.” –Expert Opinion

“For decades, surgery has been the standard approach for many patients with high-risk localized or locally advanced prostate cancer, but these data suggest it may not be enough on its own. Earlier integration of apalutamide has the potential to reshape how prostate cancer is treated by building on curative-intent surgical treatment and improving outcomes for these patients.”–Expert Opinion

Conclusion

According to global epidemiological estimates, prostate cancer remains one of the most commonly diagnosed cancers among men worldwide, with patients having high-risk localized or locally advanced disease facing a substantial risk of recurrence and metastasis despite curative-intent surgery. In the competitive landscape of prostate cancer treatments, both Bayer’s NUBEQA and Janssen’s ERLEADA are making significant strides. Currently approved for nmCRPC and mCSPC, these androgen receptor inhibitors are now setting their sights on the localized prostate cancer market. Bayer is conducting a Phase III trial of NUBEQA in combination with LHRHa and EBRT for localized very high risk prostate cancer, mirroring a similar strategy employed by Janssen with ERLEADA. While both drugs have shown promise in their approved indications, ERLEADA appears to have a slight edge in efficacy, whereas NUBEQA boasts a more favorable safety profile. The race to enter the localized prostate cancer market is heating up, with ERLEADA potentially gaining first-mover advantage, followed closely by NUBEQA. Although Phase III data for both drugs in this new indication are yet to be presented, the outcome of these trials will be crucial in determining which treatment will dominate the localized prostate cancer market. If approved, both drugs will not only shape treatment paradigms but also influence market dynamics in this highly competitive space.