TOPLINE:

Cribriform-positive morphology was associated with a 3.6-fold higher risk for metastasis in patients with prostate cancer, and radiotherapy with neoadjuvant androgen deprivation therapy (ADT) was associated with a lower long-term risk for metastasis than active monitoring, a new secondary analysis suggested. In contrast, most patients with cribriform-negative disease had favorable outcomes regardless of the initial treatment modality.

METHODOLOGY:

• Prostate cancer incidence is expected to double by 2040, underscoring the importance of early detection and management. Initial findings from the PROTECT randomized trial reported similar long-term prostate cancer-specific survival across patients who underwent active monitoring, surgery, or radiotherapy, but patients who received early treatment had fewer metastases, which suggests a need to better identify patients who may benefit from early treatment.
• Cribriform morphology is associated with poor outcomes in prostate cancer and could help identify higher-risk cases, but randomized data comparing early treatment and active monitoring in cribriform-positive and cribriform-negative prostate cancer are lacking.
• In this secondary analysis of the PROTECT trial, researchers conducted a centralized histopathologic review of 712 available diagnostic biopsy slides from the trial, which originally enrolled 1643 men with clinically localized prostate cancer (mean age, 62 years) between 1999 and 2009.
• In the intention-to-treat cohort, 34.8% of participants underwent active monitoring (n = 248), 31.9% had surgery (n = 227), and 33.3% received radiotherapy with neoadjuvant ADT (n = 237).
• Researchers evaluated the 15-year risk for metastasis among patients with cribriform-positive or cribriform-negative prostate cancer.

TAKEAWAY:

• Among 712 men whose biopsies were reviewed, 93 (13.1%) had cribriform-positive disease, and 42 (5.9%) developed metastasis over 15 years. In the intention-to-treat cohort, cribriform-positive status was associated with a significantly increased risk for metastasis (hazard ratio [HR], 3.61; P = .003).
• Compared with active monitoring, radiotherapy with neoadjuvant ADT was associated with a significantly reduced risk for metastasis over 15 years (HR, 0.35; P = .04), while surgery was delayed but was not associated with a significantly lower risk for metastasis (HR, 0.52; P = .09). Overall, among patients with cribriform-positive disease, the 15-year cumulative incidence of metastasis was 8% with radiotherapy (similar to the cribriform‑negative group) and was 26% with surgery and 25% with active monitoring (significantly higher than the respective cribriform-negative groups).
• Among patients with cribriform-negative disease, the 15-year metastasis incidence was low and did not differ meaningfully by the initial treatment modality.
• In a subgroup analysis, patients with cribriform-positive Gleason score ≥ 4 + 3 disease had the highest risk for metastasis (HR, 10.63; P < .001), followed by those with cribriform-negative Gleason score ≥ 4 + 3 disease (HR, 7.69; P < .001) and those with cribriform-positive Gleason score 3 + 4 disease (HR, 3.75; P = .03).

IN PRACTICE:

“The findings of this cohort study suggest that cribriform-positive disease confers a high risk of developing metastasis among patients with prostate cancer,” the authors of the study wrote. Although “surgery delayed but did not prevent metastasis” in patients with cribriform-positive disease, “radiotherapy with neoadjuvant ADT was associated with a reduction of the long-term incidence of metastasis compared with active monitoring.”

Overall, “our retrospective, exploratory analysis of the PROTECT trial outcomes clarifies that this excess risk was mostly concentrated in the 13.1% of patients who had cribriform-positive disease, with cribriform morphology being an independent predictor of metastasis,” the authors of the study added.

SOURCE:

The study, led by Nikita Sushentsev, MD, University of Cambridge School of Clinical Medicine, Cambridge, England, was published online in JAMA Oncology.

LIMITATIONS:

The retrospective design and lack of cribriform morphology as a randomization variable may have introduced unaccounted confounders. The relatively small number of events in the cribriform-positive subgroup limited statistical power for some analyses. The study was not designed or powered to definitively conclude superiority between treatment modalities for cribriform-positive disease.

DISCLOSURES:

The study received support from the Health Technology Assessment Program of the National Institute for Health and Care Research, with additional support from the Cancer Research UK Cambridge Centre and the National Institute for Health and Care Research Cambridge Biomedical Research Centre. Several authors reported receiving grants or personal fees and having other ties with various sources. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.