CCR scores may provide an ADT-free pathway in high-risk prostate cancer

Prognostic risk estimators that incorporate genomic data and clinical factors may enable the elimination of androgen deprivation therapy (ADT) in men with medium- or high-risk prostate cancer after radiation therapy (RT). The researchers reported.

In a retrospective study of approximately 750 men who underwent dose-escalation RT, men with a total clinical cell cycle risk (CCR) score of less than 2.112 had a 10-year risk of distant metastasis of only 4.1%. was. The National Comprehensive Cancer Network (NCCN) risk group had a 10-year risk of 25.3% above the threshold, reported by Jonathan Toward, MD, of the University of Utah in Salt Lake City.

According to the hypothetical survey results, for those with lower scores, the difference based on receipt of RT alone (4.2%) or RT and ADT (3.9%) was negligible. Urological Cancer Symposium (GUCS)..

Many studies have shown that the addition of ADT reduces the risk of metastasis in men with prostate cancer, Tward said. “Nevertheless, this clear relative benefit can be clinically suspicious if the baseline risk of metastasis in the population or individual is low.”

Tward said that about 70% of prostate cancer patients are below the threshold used in the study. That is, half of men with medium-risk prostate cancer, one in five high-risk patients, and one in 20 very high-risk patients. -High-risk illnesses may omit ADT.

The CCR score is a combination of the Cell Cycle Progression (CCP) score using the Prolaris test and the Prostate Cancer Risk Assessment (CAPRA) score of UCSF. This is age, prostate-specific antigen level, Gleason score, T-stage, and percentage of positive cores on biopsy.

A previous study established a CCR score of 2.112 as a cutoff in which men with medium-risk or high-risk prostate cancer benefited minimally from multidisciplinary treatment. There were certain restrictions, such as the RT dose and the duration of ADT not being taken into account. Also, various types of RT techniques were used and the number of radiation subsets was relatively small.

Current validation studies address these issues and show that CCR scores are a better prognostic factor for metastasis at 10 years compared to CAPRA or CCP scores alone:

• CCR: HR 2.21 (95% CI 1.70-2.87, C-index 0.78)

• CAPRA: HR 1.39 (95% CI 1.22-1.58, C-index 0.71)

• CCP: HR 2.04 (95% CI 1.48-2.79, C-index 0.69)

The CCR score was also more accurate compared to the NCCN risk subgroup (C-index 0.72). In all NCCN subgroups (favorable, unfavorable intermediate, high / very high), the risk of metastasis at 10 years was less than 5% if the patient’s CCR score was below the cutoff.

“Adding ADT to RT adds unnecessary morbidity because the absolute risk of progression-free survival is very small for many disadvantaged medium-risk men and a significant minority of high-risk men.” Said Tward.

For example, in EORTC 22991, which consisted primarily of men with non-bulky and moderate-risk illnesses, the addition of ADT reduced the absolute risk of distant metastases after 10 years from approximately 8% to 5%. About 30 people needed treatment to prevent metastasis in one case. A Recent research Tward suggested that most men want to reduce their absolute risk of metastatic disease by 5% in order to consider ADT over RT alone.

Dr. Richard Varisenti, MD, a GUCS debater at the University of California, Davis School of Medicine, warned that biomarkers have not been positively tested and have not been shown to improve long-term outcomes in men with high-risk prostate cancer.

“Clearly, according to the NCCN Risk Group, CCR scores provide very accurate individual estimates and may justify testing in stepwise, well-functioning non-inferiority studies,” he said. Stated. “Such studies may establish a highly personalized, non-enhanced approach to the treatment of prostate cancer, subject to strategies below the multi-modality threshold.”

He pointed out NRG-GU009 trialThe Decipher genomic risk classifier, which is currently underway, will be used to test such a personalized, non-enhanced approach for men with high-risk prostate cancer.

The current study examined the CCR scores of 741 evaluable patients with medium-risk (70%) or high-risk (30%) prostate cancer that were biopsy-proven, based on NCCN criteria. Tward et al. Obtained biopsy tissue years after the patient was treated and performed a retrospective genetic test to eliminate the risk of prejudice in treatment decisions. The median follow-up was 5.9 years.

Patients who received in vitro radiation therapy using the latest technology with a CT-based treatment plan and the latest dose escalation radiation (1.8 Gy per fraction> 75.6 Gy) were included. Persons receiving pelvic lymph node radiation therapy were allowed. I needed to know how and how long ADT was used.

About half of the patients were treated with ADT in combination with RT. For men who do not like medium-risk cancer, the duration of ADT is considered “sufficient” if they receive at least 4 months of ADT, and for men with high-risk cancer it is at least 18 months, and is currently Consistent with the recommendations of the NCCN guidelines. According to this criterion, less than half (44%) received ADT, but not enough.