425 patients. 48 hospitals. Real-world outcomes benchmarked against the pivotal ARCHES clinical trial.

September 2026, Cancers, an open-access, peer-reviewed journal published by MDPI, published the article:
“Enzalutamide Plus ADT for the Treatment of mHSPC: Real-World Evidence from a Bulgarian Cohort.”

This Real-World Evidence (RWE) study, co-authored by Bulgarian oncology experts, academic and reimbursement institutions, and Sqilline Health, evaluates the effectiveness of enzalutamide + androgen deprivation therapy (ADT) as first-line treatment for patients with metastatic hormone-sensitive prostate cancer (mHSPC) in routine Bulgarian clinical practice. Real-world outcomes were compared with those reported in the pivotal ARCHES clinical trial.

Powered by Sqilline’s Danny Platform, the study transformed structured and unstructured EHR data from 48 hospitals across Bulgaria into standardized, research-ready datasets. The analysis identified 425 patients treated between 2022 and 2025, including a 249-patient trial-aligned cohort for robust comparison with ARCHES.

Introduction

Prostate cancer is one of the most common malignancies in men, with metastatic disease associated with substantially poorer outcomes. ADT remains a cornerstone of treatment, while next-generation androgen receptor pathway inhibitors have transformed the management of metastatic hormone-sensitive disease.

Following the clinical benefits demonstrated in ARCHES, enzalutamide combined with ADT became an established treatment option for mHSPC. Real-world evidence is important for understanding how outcomes observed in controlled clinical trials translate into broader and more heterogeneous patient populations encountered in routine clinical practice.

Key Summary Points

Objectives

  • Evaluate the real-world effectiveness of enzalutamide + ADT as first-line treatment for mHSPC in Bulgaria.
  • Assess progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR).
  • Compare real-world outcomes with the pivotal ARCHES clinical trial.
  • Adjust for differences between the real-world and clinical-trial populations to enable meaningful comparison.

Challenges

  • Fragmented clinical data – relevant patient information was distributed across structured and free-text hospital EHRs.
  • Real-world vs. trial population differences – routine clinical populations differed from ARCHES in age, ECOG performance status, prior treatment exposure, and other characteristics.
  • Variability in routine clinical documentation – differences in response assessment and documentation complicated direct comparison with standardized clinical-trial endpoints.

Solution – Danny Platform

Danny Platform enabled:

  • AI-powered extraction, structuring and harmonization of structured and unstructured EHR data from 48 hospitals.
  • Identification of a 249-patient ARCHES-aligned cohort based on key trial eligibility criteria.
  • Application of Iterative Proportional Fitting (IPF) to balance baseline characteristics between real-world and clinical-trial populations.
  • Generation and analysis of trial-comparable PFS, OS, ORR and CBR endpoints from routinely collected clinical data.

Results

Study at a Glance

425 patients | 48 hospitals | 249 trial-aligned patients | 89.6% CBR

Patient Cohort

  • 425 patients received enzalutamide + ADT as first-line treatment.
  • Study period: 2022–2025
  • 249 patients (58.6%) met the main ARCHES eligibility criteria.
  • 176 patients (41.4%) formed the non-eligible real-world group.

Real-World Population

Compared with ARCHES, the real-world population was older and differed in several baseline characteristics:

  • Median age: 74 vs. 70 years
  • Patients aged ≥75: 47.4% vs. 29.6%
  • ECOG 1: 71.9% vs. 21.8%
  • Gleason score ≥8: 67.6% vs. 69.3%
  • High-volume disease: 54.6% vs. 61.7%
  • Median PSA at treatment initiation: 48.5 vs. 5.4 ng/mL

Trial-Aligned Survival Outcomes

Following IPF adjustment, PFS and OS were broadly comparable with ARCHES during follow-up periods with sufficient patients at risk.

Progression-Free Survival

  • 6 months: 91% RWE vs. ~94% ARCHES
  • 12 months: 82% vs. 83%
  • 18 months: 79% vs. ~75%
  • 24 months: 74% vs. ~73%

Overall Survival

  • 6 months: 98% RWE vs. ~99% ARCHES
  • 12 months: 90% vs. 96%
  • 18 months: 89% vs. ~91%
  • 24 months: 88% vs. 86%

Median PFS and OS were not calculable during the available follow-up. Later time-point comparisons should be interpreted cautiously because fewer real-world patients remained at risk.

Real-World Data Insight

The study reported a CBR of 89.6% in the real-world cohort vs. 95.9% in ARCHES, while ORR was 12.3% vs. 85.9%.

The authors highlight differences in routine response documentation as an important factor when interpreting the ORR comparison. In real-world practice, patients were frequently recorded as having stable disease rather than standardized complete or partial responses, illustrating one of the methodological challenges of comparing routinely collected EHR data with clinical-trial endpoints.

Why It Matters

The study demonstrates that routinely collected hospital data can be transformed into trial-comparable real-world evidence at national scale.

By structuring heterogeneous EHR data, identifying trial-aligned patient cohorts, balancing population differences and deriving clinical outcomes, Danny Platform provides an infrastructure for generating robust RWE from routine oncology care.

For pharma and research partners, this type of infrastructure can support use cases such as treatment effectiveness studies, post-authorization evidence generation and contextualization of clinical-trial results.

Conclusions

  • Real-world outcomes with enzalutamide + ADT were broadly consistent with ARCHES during the more robust follow-up periods.
  • The study provides evidence from an older and more heterogeneous real-world population than the clinical-trial cohort.
  • The analysis highlights the importance of accounting for differences in populations and routine clinical documentation when comparing RWE with clinical trials.
  • Danny Platform demonstrated its ability to transform multi-hospital EHR data into standardized, research-ready evidence and enable trial-aligned comparative RWE analyses at national scale.

Authors & Affiliations

  • Manoela Manova, Boryana Ivanova, Alexandra Savova – Medical University – Sofia & National Council on Prices and Reimbursement of Medicinal Products (NCPRMP), Bulgaria
  • Antoan Rangelov – Sofia University “St. Kliment Ohridski” & NCPRMP, Bulgaria
  • Mila Petrova – Medical Oncology Clinic, MHAT Nadezhda, Sofia, Bulgaria
  • Assen Dudov, Ivsan Chan, Sevil Ahmed, Victor Nenov, Elitsa Varbanova -Medical Oncology Clinic, Acibadem City Clinic Mladost, Sofia, Bulgaria
  • Todor Georgiev, Daniel Penchev – Sqilline Health, Sofia, Bulgaria

👉 Read the Full Publication

“Enzalutamide Plus ADT for the Treatment of mHSPC: Real-World Evidence from a Bulgarian Cohort”
Cancers, 2026, 18, 3007