Use of the cell cycle progression (CCP) score for predicting systemic disease and response to radiation of biochemical recurrence

Abstract

Abstract. BACKGROUND: Determining the optimal treatment for biochemical recurrence (BCR) after radical prostatectomy (RP) is challenging. OBJECTIVE: We evaluated the ability of CCP score (a prognostic RNA expression signature) to discriminate between systemic disease and local recurrence in patients with BCR after RP. METHODS: Sixty patients with BCR after RP were selected for analysis based on: 1) metastatic disease, 2) non-response to salvage external beam radiotherapy (EBRT), and 3) durable response to salvage EBRT. CCP scores were generated from the RNA expression of 46 genes. Logistic regression assessed the association between CCP score and patient group. RESULTS: Passing CCP scores were generated for 47 patients with complete clinical and pathologic data. CCP score predicted clinical status when comparing patients with metastatic disease or non-responders to salvage therapy to patients with durable response (p = 0.006). CCP score remained significantly predictive of clinical status after accounting for time to BCR, PSA level at BCR, and Gleason score (p = 0.0031). CONCLUSIONS: Elevated CCP score was associated with increased risk of systemic disease, indicating that CCP score may be useful in identifying patients with BCR who are most likely to benefit from salvage radiation therapy.

Prognostic utility of biopsy‐derived cell cycle progression score in patients with National Comprehensive Cancer Network low‐risk prostate cancer undergoing radical prostatectomy: implications for treatment guidance

“…Previous studies performed in more diverse patient populations have demonstrated a similar association of CCP score with various long‐term outcomes, including metastatic disease and PCa death . For example, in a heterogeneous cohort of patients with low‐ (32%) to intermediate‐/high‐risk (68%) PCa, Bishoff et al demonstrated a nearly 50% increase in the risk of BCR after RP (HR 1.47, 95% CI 1.23–1.76; P < 0.001) and a more than fourfold increase in the risk of metastatic disease (HR 4.19, 95% CI 2.08–8.45; P < 0.001) with a one‐point increase in biopsy‐derived CCP score.…”

“…In the present study, over one‐third of low‐risk patients had CCP scores >0, putting them at an appreciable risk of BCR after RP. Based on previous studies, these men likely harbour tumours with more aggressive underlying biology, and as such may not be as well suited for conservative management as their clinical and pathological features suggest . Nevertheless, it is important for healthcare providers to remember that the results of genetic tests, such as the CCP score, must be used in conjunction with other clinical information and patient demographics in order to create a stronger understanding of the overall clinical picture and underlying disease aggressiveness.…”

“…Tissue‐based genomic tests, such as the cell cycle progression (CCP) score, can help decrease prognostic uncertainty and improve risk stratification of GS6 PCa . Previous studies have shown that CCP scores measured in prostate biopsy and radical prostatectomy (RP) specimens were predictive of several clinical outcomes ; however, it is currently unclear whether the CCP score improves clinical risk stratification within NCCN low‐risk PCa or GS6 tumours more generally. The aim of the present study, therefore, was to determine the prognostic utility of the CCP score derived from prostate biopsies of men with low‐risk PCa who underwent RP.…”

Tissue-based biomarkers in prostate cancer

“…Another study also evaluated RP specimens in a smaller cohort and found increased CCP score was associated with increased risk of systemic disease in those with BCR after RP, which may help identify those most likely to benefit from earlier salvage therapy. [61]…”

Cell‐cycle risk score more accurately determines the risk for metastases and death in prostatectomy patients compared with clinical features alone

“…When CCP gene expression was added to other clinicopathologic features, the combined model was a significantly better predictor of recurrence than clinicopathologic features alone 9 . This observation has subsequently been validated in many independent cohorts, 10–14 including in patients following radical prostatectomy 15,16 . In fact, Cooperberg et al 15 validated a predefined model (clinical cell‐cycle risk [CCR] score) that combines the CCP score and the postsurgical Cancer of the Prostate Cancer Risk Assessment (CAPRA‐S) for determining patient prognosis post‐prostatectomy 15 .…”