Validation of the 3-variable prognostic score (3-PS) in mCRPC patients treated with 223Radium-dichloride: a national multicenter study

Abstract

Objective Radium-223 (223Ra) has been approved for treatment in patients with metastatic castration-resistant prostatic cancer (mCRPC) and bone metastasis. This α-emitting radionuclide has a beneficial effect on pain and is also capable to increase overall survival (OS). Several studies evaluated the prognostic value of different biomarkers at baseline, such as serum values, imaging parameters or pain. To date, however, clinicians lack a validated and simple system to assess which patients will most likely benefit from 223Ra treatment. The 3-variable prognostic score (3-PS), proposed in a single-center study in 2017 classifies patients in five prognostic groups with a specific OS. This study aims to validate the 3-PS in a larger multicenter population. Methods Four hundred and thirty mCRPC patients treated with 223Ra from six different centers were analyzed. The 3-PS score consists of the collection of baseline hemoglobin, prostatic specific antigen and Eastern cooperative oncology group performance status and was initially applied to the whole population (total group). The score was then validated on the 338 patient’s subgroup (clean group) obtained by subtracting the 92 patients enrolled for the original study of the 3-PS score. This purified group served as further validation evidence. Results Statistical analysis showed that the 3-PS score was valid on the total group as well as in the clean group as the AUC estimated (0.74) falls within the CI of the AUC calculated on the validation sample (95% CI 0.66–0.82). Conclusion This study confirms the validity of the 3-PS score for mCRPC patients. This score is simple, noninvasive and affordable and can be easily used to select patients that will most probably complete 223Ra treatment. In addition, this tool provides an exact estimate of life expectancy in terms of OS.

The prognostic power of inflammatory indices and clinical factors in metastatic castration-resistant prostate cancer patients treated with radium-223 (BIO-Ra study)

“…Two previous studies have proposed integrating three prognostic biomarkers to obtain a 3-variable predicting score based on baseline ECOG PS, PSA, and Hb serum levels in mCRPC patients treated with [ 223 Ra]RaCl 2 [ 8 , 45 ]. These studies were conducted on 92 and 430 patients, respectively.…”

A single-center, multidisciplinary experience with radium-223 dichloride in men with metastatic castrate-resistant prostate cancer

“…In other retrospective studies of 223 Ra [11][12][13][14]18 , 21 , clinical and baseline laboratory parameters and their changes during treatment showed varying associations with OS (Table VI). However, similar to our results, most authors found at least some association between OS and baseline Hb, tALP, and ECOG PS.…”

“…The bone selective, calcium mimetic radium-223 dichloride (Ra-223) is a short-range, alpha particle emitter that showed a 3.6-month OS benefit over placebo in the ALSYMPCA trial 7 , with limited toxicity up to 3 years after treatment 8 . Various studies that followed aimed to determine whether specific parameters could help predict response to 223 Ra and survival [9][10][11][12][13] , such as the baseline Eastern Cooperative Oncology Group (ECOG) performance status (PS), prostate-specific antigen (PSA), and hemoglobin (Hb), which have been validated 14 . Additionally, the ALSYMPCA trial demonstrated that 223 Ra therapy reduced pain and delayed the time to first palliative external beam radiation treatment (EBRT) 7,15 .…”

Radium-223 Treatment of Patients with Metastatic Castration Resistant Prostate Cancer: Biomarkers for Stratification and Response Evaluation

“…CTC count is considered a prognostic factor in mCRPC patients, as a higher CTC count is associated with a worse outcome [102]. In patients treated with Ra-223, a CTC count ≤5 in 8 mL blood at baseline is predictive for completing the full course of Ra-223 cycles [59,77,78]. Another study suggested that patients with a CTC count <5 have a better OS compared to patients with a CTC count of ≥5 when treated with Ra-223, which underlines its prognostic value [79].…”

“…Obviously, the number of Ra-223 cycles received is not an independent biomarker. Patients that received one to four cycles were usually those with a poor baseline status, including a low performance status and baseline hemoglobin [78,84]. Moreover, receiving more Ra-223 cycles was related to better PFS, which suggests predictive biomarker qualities of the number of Ra-223 cycles received.…”