A microscopic pattern in tumour cells – rarely reported until recently – could influence how doctors decide who may benefit from robotic surgery, according to cancer specialists at University College London Hospitals NHS Foundation Trust (UCLH).
A specific arrangement of prostate cancer cells called cribriform pattern tends to point to a more dangerous or aggressive type of cancer and could influence the decision to treat early tumours with surgery, UCLH cancer surgeons have said.
Writing in the BJU International journal, Ben Lamb and Prabhakar Rajan, both UCLH consultant urological surgeons, say cribriform pattern is an important piece of information that should be factored into every treatment conversation for intermediate-risk prostate cancer.
Most prostate cancer is already graded using the Gleason score, a well-established system that helps predict how aggressively a tumour is likely to behave. But the system does not routinely capture cribriform pattern, so named for the sieve-like structure formed by sheets of cancer cells punched through with multiple holes.
Although the pattern has been classified as a high-risk feature since 2014, guidelines only began formally requiring pathologists to report it in 2019. The result is that cribriform status has often been overlooked when treatment decisions are made, the authors said.
In their comment piece, the four authors (who include colleagues from Barts Health NHS Trust and Queen Mary University of London) assessed the findings of two new analyses of the data from the landmark ProtecT trial, one published in JAMA Oncology last year and the other published in BJU International earlier this month. The two papers have revisited the biopsy slides from the ProtecT trial with fresh eyes, specifically looking at whether cribriform pattern was present.
The ProtecT trial was one of the largest studies of its kind, and followed 1,643 men with non-metastatic prostate cancer over 15 years, comparing outcomes for those who received radiotherapy, surgery, or active monitoring (a predecessor to active surveillance). A key finding was that, for many men, active monitoring produced similar survival rates as immediate treatment, with significantly better quality of life. This has encouraged a broader shift away from treating all prostate cancers aggressively.
But in last year’s analysis, researchers reviewed biopsy slides from 712 trial participants. Of these, 13.1 per cent were found to have cribriform-positive disease, something that had not been identified or considered when those patients were originally managed. Among men with cribriform-positive disease, the 15-year risk of developing metastatic cancer (cancer that has spread to other parts of the body) was 3.6 times higher than in those whose cancer was cribriform-negative.
In this year’s analysis of surgically treated patients from ProtecT, all cases of disease progression or prostate cancer death occurred exclusively in patients with cribriform-positive disease, particularly those with more advanced grade group 3 disease or seminal vesicle invasion (where cancer has spread to nearby glands).
“These findings suggest we need to take a much harder look at patients whose biopsies show cribriform pattern. The data points towards earlier, more active treatment,” said Mr Lamb.
One of the key arguments is that the Gleason score, while useful, may be insufficient on its own as a guide to treatment. Cribriform pattern sits within Gleason pattern 4, but not all pattern 4 disease is the same. Other research has shown that cribriform glands vary in their aggressiveness depending on their size and subtype, something the current scoring system does not capture.
The authors suggest that a future classification approach, distinguishing between ‘Favourable’ and ‘Unfavourable’ intermediate-risk disease, and already adopted in some US pathology centres, may be needed to ensure patients with cribriform-positive disease receive appropriate risk assessment and treatment planning.
The authors also highlight a systems problem: even though four major international guidelines — including those of the Royal College of Pathologists — now recommend that cribriform status be reported, it is not always documented or communicated to treating clinicians. The size of cribriform glands, which may indicate how aggressive the cancer is, is not routinely required to be reported at all.
They call for improvements in MRI scanning to better detect seminal vesicle invasion — a feature they identified as one of the strongest predictors of poor outcomes in surgically treated patients.
“The Gleason score has served us well, but this research is further evidence that it doesn’t tell the whole story. And while pathology reporting guidelines have moved in the right direction, implementation is inconsistent. We need to ensure that cribriform status is reliably communicated to the multidisciplinary team making treatment decisions and also to patients,” Prof Rajan said.
The specialists are careful to stress that these two publications are hypothesis-generating rather than definitive. The number of cribriform-positive patients in the ProtecT trial (93) was too small to reach statistical significance in all comparisons between treatment arms. They are clear that larger, dedicated clinical trials are now needed.
But they conclude that for patients with cribriform-positive disease and especially those with higher-grade tumours, clinicians should carefully consider active treatment.
