PCa Game Changer Session examines ARANOTE and SPCG-13

During the lecture “Prostate-Specific Antigen (PSA) response with darolutamide plus Androgen-Deprivation Therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) in ARANOTE”, presenter Prof. Fred Saad (CA) concluded that darolutamide provided deep and durable PSA responses in the overall population and across all baseline PSA subgroups. Three times as many patients achieved undetectable PSA (<0.02ng/mL) vs placebo. Undetectable PSA was achieved in a significantly higher proportion of patients regardless of baseline PSA.

Undetectable PSA with darolutamide correlated with clinical benefits regarding radiological progression or death and longer times to metastatic castration-resistant prostate cancer (mCRPC) and PSA progression. “The flipside is that in those patients who are less likely to reach undetectable PSA, we may need to consider triplet therapy instead of doublet therapy or monotherapy,” stated Prof. Saad. He added that the safety profile of darolutamide was consistent across subgroups, regardless of PSA response and baseline PSA.

Discussant Dr. Elena Castro (ES) addressed one of the criticisms of the ARANOTE study—the use of ADT alone in the control arm. “During the recruitment period from 2021 to 2022, we had evidence of the benefits of intensified therapy. Unfortunately, evidence and access to other therapies do not necessarily translate into their use in clinical practice. The most recent data I found on different treatments for mHSPC in the U.S. – where access to these therapies is generally good – showed that during the recruitment period, 50% of patients were still receiving ADT as monotherapy. Fortunately, this is changing. We see a trend toward more intensified therapy in mHSPC. We are moving in the right direction, thanks to the work of Prof. Saad, his colleagues, and many others, who are contributing to the field.”

In “Adjuvant docetaxel versus surveillance in intermediate- or high-risk prostate cancer after radical curative radiotherapy: the final 10-year survival results of the SPCG-13 trial”, presenter Prof. Pirkko-Liisa Kellokumpu-Lehtinen (FI) shared that the 10-year survival was long, with a median of 14.5 years in the surveillance group and not yet reached in the docetaxel group, with no statistically significant difference between the groups. Furthermore, the high-Gleason group of patients tended to gain from docetaxel. She added that better predictive markers are needed to select early prostate cancer patients for adjuvant treatments.

Prof. Kellokumpu-Lehtinen stated, “Docetaxel has shown to be effective in hormone-naive metastatic prostate cancer (i.e., STAMPEDE and CHARTEED), but why not effective in the earlier phase, to resolve this we need further clinical trials and better predictive markers.”

What does this trial add? Discussant Dr. Alison Tree (GB) stated that it is a large, well-conducted, randomised trial that demonstrated no evidence of benefit to adding docetaxel.

According to Dr. Tree, while docetaxel is known to be active in M1 disease, evidence of overall survival (OS) benefit in non-metastatic patients remains inconsistent. It is likely to be superseded by androgen receptor pathway inhibitors (ARPIs), which are better tolerated. “We await the results of ATLAS, ENZARAD, and DASL-HiCaP,” stated Dr. Tree.

Webcasts, videos, posters, and full-text abstracts are accessible via the EAU25 Resource Centre.