3 januari 2026: Bron: Jama Oncology

Uit een nieuwe analyse van de gerandomiseerde Protect studie blijkt dat prostaatkankerpatiënten met een Gleasonscore van 7 of hoger die bij de diagnose een Cribriform positieve expressie lieten zien deze grotere kans hadden op uitzaaiingen in andere organen en/of lymfklieren in vergelijking met de prostaatkankerpatiënten die bij de diagnose een Cribriform negatieve expressie hadden.

In deze secundaire analyse van de 15-jarige resultaten van de Protect studie bedroeg de cumulatieve incidentie van uitzaaiingen respectievelijk 25%, 26% en 8% voor mannen met Cribriform-positieve prostaatkanker die waren toegewezen aan actieve monitoring, chirurgie en radiotherapie met neoadjuvante hormoontherapie (ADT). In vergelijking: Bij mannen met Cribriform-negatieve prostaatkanker traden uitzaaiingen op bij respectievelijk 7%, 4% en 3% in elke groep.

Het primaire doel van deze 15-jarige studie was het meten van ziekteprogressie naar uitgezaaide ziekte (botuitzaaiingen, viscerale of lymfekliermetastasen op scanbeelden te zien of een meting van de PSA >100 ng/ml).

De resultaten uit het abstract vertaald:

Resultaten:

Van de 712 mannen (gemiddelde leeftijd, 62,0 [5,0] jaar) van wie de biopten retrospectief werden beoordeeld, hadden 93 patiënten (13,1%) een cribriforme positieve ziekte en ontwikkelden 42 patiënten (5,9%) uitzaaiingen.
In de intention-to-treat-cohort verhoogde een Cribriform positieve ziekte het risico op uitzaaiingen significant (hazard ratio , 3,61 [95% CI, 1,60-8,11]; P = 0,003).
Radiotherapie met neoadjuvante hormoontherapie (ADT) verminderde het risico op uitzaaiingen significant (HR, 0,35 [95% CI, 0,16-0,78]; P = 0,04) (cumulatieve incidentie na 15 jaar bij patiënten met Cribriform positieve tumoren: 8%), terwijl chirurgie de uitzaaiingen vertraagde, maar de langetermijn resultaten niet significant verbeterde in vergelijking met actieve monitoring (HR, 0,52 [95% CI, 0,25-1,08]; P = 0,09) (cumulatieve incidentie na 15 jaar bij patiënten met Cribriform tumoren: 26% voor chirurgie en 25% voor actieve monitoring).
Bij patiënten met Cribriform negatieve ziekte was de incidentie van uitzaaiingen laag en verschilde deze niet per behandeling.

Conclusie:

Deze bevindingen suggereren dat patiënten met cribriform-negatieve prostaatkanker een laag risico hebben op uitzaaiingen op de lange termijn, ongeacht de initiële behandeling, terwijl patiënten met cribriform-positieve prostaatkanker een hoog risico hebben op uitzaaiingen, dat mogelijk wordt verlaagd bij patiënten die radiotherapie met neoadjuvante hormoontherapie (ADT) krijgen.

Het volledige studierapport is tegen bepaalde voorwaarden gratis in te zien. Hier het abstract van deze studie:

Active Monitoring, Surgery, and Radiotherapy for Cribriform-Positive and Cribriform-Negative Prostate CancerA Secondary Analysis of the PROTECT Randomized Clinical Trial

Key Points

Question What is the long-term incidence of metastasis in patients with cribriform-positive and cribriform-negative prostate cancer who undergo active monitoring, surgery, or radiotherapy?

Findings In this secondary analysis of the 15-year outcomes of the PROTECT trial, the cumulative incidence of metastasis was 25%, 26%, and 8% for men with cribriform-positive prostate cancer assigned to active monitoring, surgery, and radiotherapy with neoadjuvant androgen deprivation therapy (ADT), respectively. For men with cribriform-negative disease, metastasis occurred in 7%, 4%, and 3% in each group, respectively.

Meaning These findings suggest that patients with cribriform-negative prostate cancer are at low risk of long-term metastasis regardless of baseline treatment, whereas patients with cribriform-positive prostate cancer are at high risk of metastasis that is potentially reduced in those receiving radiotherapy with neoadjuvant ADT.

Abstract

Importance Cribriform prostate cancer is associated with poor outcomes; however, its optimal treatment strategy remains unclear in the absence of randomized data.

Objective To retrospectively analyze the results of the PROTECT randomized clinical trial to establish the association between cribriform-positive and cribriform-negative prostate cancer and 15-year risk of metastasis in patients who underwent active monitoring, surgery, or radiotherapy.

Design, Setting, and Participants Between 1999 and 2009, the PROTECT phase 3 randomized clinical trial enrolled 1643 men with clinically localized prostate cancer who were randomly assigned to receive active monitoring, surgery, or radiotherapy with neoadjuvant androgen deprivation therapy (ADT). In this secondary analysis of the PROTECT trial, a centralized histopathologic review was conducted on available diagnostic biopsy slides to classify patients as cribriform-positive if they had invasive cribriform carcinoma and/or intraductal carcinoma. Data were collected from January 25, 2024, to October 11, 2024, and were analyzed from October 14, 2024, to January 30, 2025.

Exposures Age, prostate-specific antigen (PSA), Gleason score, and cribriform status.

Main Outcomes and Measures The primary outcome was progression to metastatic disease (bony, visceral, or lymph node metastases on imaging or PSA >100 ng/mL). Multivariable Cox proportional hazards regression models, adjusted for randomization variables, were incorporated to assess 15-year metastasis risk. Cumulative incidence curves were compared using the Gray test. Both intention-to-treat and per-protocol analyses were performed.

Results Among 712 men (mean age, 62.0 [5.0] years) whose biopsies were retrospectively reviewed, 93 (13.1%) had cribriform-positive disease and 42 (5.9%) developed metastasis. In the intention-to-treat cohort, cribriform-positive disease significantly increased the risk of metastasis (hazard ratio , 3.61 [95% CI, 1.60-8.11]; P = .003). Radiotherapy with neoadjuvant ADT significantly reduced metastasis risk (HR, 0.35 [95% CI, 0.16-0.78]; P = .04) (15-year cumulative incidence in patients with cribriform-positive disease, 8%), while surgery delayed metastasis but did not significantly improve long-term outcomes compared with active monitoring (HR, 0.52 [95% CI, 0.25-1.08]; P = .09) (15-year cumulative incidence in patients with cribriform-positive disease, 26% for surgery and 25% for active monitoring). Among patients with cribriform-negative disease, incidence of metastasis was low and did not differ by treatment. Similar per-protocol results were noted.

Conclusions and Relevance The findings of this secondary analysis of the PROTECT randomized clinical trial suggest that cribriform morphology was a strong, independent predictor of 15-year metastasis among patients with prostate cancer and that radiotherapy with neoadjuvant ADT was associated with a reduced long-term risk of metastasis. Conversely, outcomes were favorable for most patients with cribriform-negative disease, supporting their eligibility for active surveillance.

Trial Registration ClinicalTrials.gov Identifier: NCT02044172

Conflict of interest statement

Conflict of Interest Disclosures: Dr Sushentsev reported receiving personal fees from Lucida Medical Ltd outside the submitted work. Dr Colling reported receiving grants from MDXHealth Commercial, UK Research and Innovation, and NHSX (for the ARTICULATE PRO study) outside the submitted work; serving as coauthor of the 2024 RCPath (UK) prostate cancer pathology reporting guidelines; receiving partial salary from the National Health Service; receiving a stipend from Clarendon; and working previously with PathLAKE and PathLAKE+. Dr Verrill reported receiving grants from the National Institute for Health and Care Research (NIHR) Oxford Health Biomedical Research Centre during the conduct of the study and serving as principal investigator of the ARTICULATE PRO study and working previously with PathLAKE and PathLAKE+ outside the submitted work. Dr Seibert reported receiving grants from GE Healthcare and Blue Earth Diagnostics; receiving personal fees from Varian Medical Systems, MJH Life Sciences, GE Healthcare, Blue Earth Diagnostics, and Cortechs.ai; receiving nonfinancial support from Quibim; and receiving stock options for advisory board participation from Cortechs.ai outside the submitted work. Dr Bryant reported receiving grants from Cancer Research UK, The Urology Foundation, and the NIHR Health Technology Assessment outside the submitted work. Dr Donovan reported receiving grants from the NIHR during the conduct of the study. Dr Neal reported receiving grants from Cancer Research UK during the conduct of the study. Dr Hamdy reported receiving grants from the NIHR (PROTECT trial chief investigator) during the conduct of the study and receiving personal fees from Intuitive Surgical, Recordati, Pfizer, and Ipsen outside the submitted work. No other disclosures were reported.

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