EAU 2021: cN+ and Systemic Treatment: More than ADT Is Needed as Systemic TTT: Yes!

(UroToday.com) In the Guideline Session II: Prostate Cancer: cN+ in newly diagnosed patients during the 2021 European Association of Urology meeting, Maria De Santis argues the point of view that more than ADT is required as systemic therapy for patients with clinically node-positive prostate cancer. She notes the challenges of this argument as there is little data, most of which is low-level evidence. However, she feels the goals of treatment intensification will improve the strategies and lives of our patients by utilizing multimodal therapy, providing alternative strategies, and treating the patient earlier.

The data she reviewed focused on the subgroup analyses from STAMPEDE and GETUG-12. STAMPEDE,1 a multi-arm protocol, includes node-positive newly diagnosed prostate cancer or relapsing after primary local therapy. Unfortunately, other mHSPC trials (CHAARTED, LATITUDE, TITAN, ENZAMET, ARCHES) did not include node-positive patients so they cannot contribute to this discussion.

The specific arm of the STAMPEDE study she focused on was the addition of abiraterone acetate (AAP) to Standard of Care ADT  vs. ADT alone. This was previously presented at ESMO 2020. This data showed an overall survival benefit for the SOC + abiraterone arm.

However, she focused on the N1M0 cohort of patients with newly diagnosed prostate cancer. These represented approximately 20% of both arms of the study.

On subgroup analysis, as seen below, node-positive men had significant OS benefit favoring the addition of AAP (though I believe this includes men with or without metastatic disease). 

deSantis_EAU21_Figure1.png

Moving on to the GETUG-12 study, which was presented at ESMO 2018, she noted that randomized patients to either ADT with local treatment alone or local treatment and docetaxel/estramustine. Approximately 29% of both cohorts had node-positive patients, similar to STAMPEDE.

On subgroup analysis, the cohort of node-positive patients also had significant RFS benefit comparable to the cohort as a whole (HR 0.64).

In a meta-analysis by Vale et al.2 of all docetaxel with ADT trials for high-risk localized prostate cancer, they noted an RFS benefit with the addition of docetaxel (HR 0.70, p<0.0001).

Based on this limited data, she concludes that:

  1. Docetaxel and AAP added to ADT is still experimental for localized and N+ prostate cancer
  2. Evolving evidence that in the highest risk localized prostate cancer, additional systemic therapy (chemo or novel hormonal) may improve outcomes. - 

                Based on this, we can extrapolate data for node-positive disease

  3. Ongoing trials (PEACE2, ENZARAD) for high-risk localized disease are exploring multimodal therapy including systemic treatment with more than ADT

Presented By: Maria De Santis, MD, Medical Oncologist, Charité Medical University Hospital, Berlin, Germany

Written By: Thenappan (Thenu) Chandrasekar, MD – Urologic Oncologist, Assistant Professor of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, @tchandra_uromd on Twitter during the 2021 European Association of Urology, EAU 2021- Virtual Meeting, July 8-12, 2021.

References: 

  1. James, Nicholas D., Johann S. de Bono, and Melissa R. Spears et al. 2017. "Abiraterone For Prostate Cancer Not Previously Treated With Hormone Therapy". New England Journal Of Medicine 377 (4): 338-351. doi:10.1056/nejmoa1702900.
  2. Vale, Claire L, Sarah Burdett, and Larysa H M Rydzewska et al. 2016. "Addition Of Docetaxel Or Bisphosphonates To Standard Of Care In Men With Localised Or Metastatic, Hormone-Sensitive Prostate Cancer: A Systematic Review And Meta-Analyses Of Aggregate Data". The Lancet Oncology 17 (2): 243-256. doi:10.1016/s1470-2045(15)00489-1.


Read the Opposing Debate: 
EAU 2021: cN+ and Systemic Treatment: More than ADT Is Needed as Systemic TTT: No!