medwireNews: The clinical cell-cycle risk (CCR) score is able to accurately predict metastasis risk in men undergoing dose-escalated radiation therapy, with or without androgen deprivation therapy (ADT), for intermediate- to high-risk localized prostate cancer, research suggests.
Jonathan Tward (Huntsman Cancer Institute at the University of Utah, Salt Lake City, USA) told delegates of the 2021 Genitourinary Cancers Symposium that the CCR provides “clinically actionable information.”
Indeed, the findings suggest that “[m]en with scores below the multimodality threshold may not significantly reduce their 10-year risk of metastasis with the addition of ADT,” and therefore the score may be used to inform the shared decision-making process between the patient and radiation oncologist, he said.
The presenter explained that the CCR combines the cell-cycle proliferation (CCP) score with the University of California San Francisco Cancer of the Prostate Risk Assessment (UCSF CAPRA) scale, which assesses risk on the basis of clinical variable such as age, prostate-specific antigen levels, and Gleason score.
In a previous study comprising men who underwent surgery and radiotherapy, the researchers established a CCR threshold of 2.112 points, such that patients with a lower score could omit multimodality therapies, he added.
The current validation study included 741 participants of a multi-institutional cohort who had biopsy-confirmed US National Comprehensive Cancer Center (NCCN) intermediate-, high-, or very high-risk localized prostate cancer and were treated with external beam radiation therapy equivalent to a minimum of 75.6 Gy at 1.8 Gy per fraction (84% received ≥79.2 Gy) with or without ADT.
In all, 47% of patients did not receive ADT, and of those who did, 55% underwent treatment for the guideline-recommended duration for their NCCN risk group, while 44% received an insufficient duration of ADT.
As reported by Tward, the CCR was better at predicting the risk for metastasis within 10 years of diagnosis than the NCCN risk, CAPRA, and CCP scores alone, with a concordance index of 0.78 versus 0.72, 0.71, and 0.69, respectively.
Among the 370 patients with a CCR score below the previously identified threshold, the 10-year risk for metastases was 4.2%, whereas the risk was 25.3% for the 371 patients with a score above this threshold.
Of note, among men with a CCR score below the threshold, the 10-year metastasis risk was a comparable 3.9% and 4.2% for those who did and did not receive ADT alongside radiation, respectively. Tward therefore noted that “the relative risk reduction one would expect by adding ADT may not be clinically significant to most patients given the very low baseline absolute risk.”
The risk for metastasis remained below 5% among patients with a CCR score below the threshold regardless of whether they received the recommended duration of ADT or insufficient ADT, whereas for men with scores above the threshold, the metastasis risk was consistently around 25% irrespective of the treatment received, reported Tward.
A similar pattern was seen when patients were stratified by NCCN risk group, suggesting that “NCCN risk groups no longer prognosticate a risk of metastasis below the CCR score threshold,” commented the presenter.
Discussant Richard Valicenti (UC Davis School of Medicine, Sacramento, USA) remarked that “the risk of metastasis was in a range that some clinicians would feel comfortable omitting androgen suppression for intermediate- and high-risk prostate cancer patients undergoing radiation therapy.”
He added, however, that “widespread acceptance for routine use faces challenges since no biomarker has been prospectively tested or shown to improve long-term outcome.”
Nevertheless, Valicenti believes that “the CCR score may provide highly precise, personalized estimates and justifies testing in tiered and appropriately powered noninferiority studies according to NCCN risk groups.”
He continued: “Such studies could establish a highly individualized de-intensified approach to treat prostate cancer, conditioned on a below the multimodality threshold strategy.”
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2021 Genitourinary Cancers Symposium; 11–13 February