Prolaris
Cell-cycle score in newly diagnosed, localized prostate cancer before treatment begins. It answers two questions: is active surveillance defensible? And does this patient need multimodal therapy?
You receive two numbers and two thresholds. The Prolaris Molecular Score measures proliferation in the cell cycle and lies clinically between 1.8 and 8.7. The Combined Clinical Risk Score (CCR) adds the clinical variables; its range runs from 0.3 to 4.2. The CCR is the decisive one, because the validated thresholds hang on it.
The report answers two questions at once, under two different assumptions. The first is the ten-year risk of dying from the tumour if left untreated — to which the active-surveillance threshold at 3.2 % DSM belongs. The second is the ten-year risk of metastasis under single-modal therapy, with the multimodal threshold at 8.8 % METs.
The concrete benefit of adding ADT is shown most clearly by the Number Needed to Treat. Above the multimodal threshold, adding ADT to radiation lowers the ten-year metastasis risk by an average of 8.2 percent: twelve men are treated for one of them to benefit. Below the threshold it is only 0.86 percent, and the number rises to 116. The score thus shows not only who needs more therapy, but also whom it can be spared.
A final note on the scale: the relationship is multiplicative, not additive. A one-unit difference in score is therefore no small difference.
Sixty percent tumour content on a 5-µm section is required. We look at the H&E section ourselves, mark the tumour and enrich it by manual microdissection under visual control — not with the scalpel by eye. That is why we meet the requirement reliably, even with very small cores. Scant tumour is rarely a reason for us to decline a case.
Decalcified material we can generally process, provided it was EDTA-decalcified — EDTA spares the nucleic acids, whereas strong acids fragment them. FFPE sections keep for up to six months, at 2–8 °C as well as at room temperature.
The report comes in English and runs to three pages: management recommendation and CCR on page 1, both scores with their ranges and thresholds on page 2, and on page 3 the placement against the median of the NCCN risk group. Signed by a specialist in pathology.
Two limitations we prefer to name ourselves. The stratification graph on page 3 rests predominantly on US patients and the NCCN classification. And if a score lies outside the validated range, we do not report it — such values may be an artefact or a technical error. You will then hear from us, rather than receive a figure we do not trust ourselves.
The published cohorts derive from the 46-gene version; we work with the decentralized 16-gene kit. That the evidence transfers is shown by the bridging study: the scores of the two versions correlate at r = 0.969 with a bias of 0.217.
- Cuzick J, et al. Prognostic value of a cell cycle progression signature for prostate cancer death in a conservatively managed needle biopsy cohort. Br J Cancer. 2012;106(6):1095-9. PMID 22361632
- Cuzick J, et al. Validation of an RNA cell cycle progression score for predicting death from prostate cancer in a conservatively managed needle biopsy cohort. Br J Cancer. 2015;113(3):382-9. PMID 26103570
- Tward J, et al. The Clinical Cell-Cycle Risk (CCR) Score Is Associated With Metastasis After Radiation Therapy and Provides Guidance on When to Forgo Combined Androgen Deprivation Therapy With Dose-Escalated Radiation. Int J Radiat Oncol Biol Phys. 2022;113(1):66-76. PMID 34610388
- Kuhl V, et al. Development and validation of a cell cycle progression signature for decentralized testing of men with prostate cancer. Biomark Med. 2022;16(6):449-59. PMID 35321552
A conversation before the first case
Fixation, shipping, and how the report reads in your clinic. Half an hour now can spare a re-biopsy.