Charlson comorbidity index predicts chronic rather than acute radiation therapy induced toxicity in men with prostate cancer
Ghanem A, Khedr G, Khalil R, Tang A, Elsaid A, Chetty I, Movsa B, and Elshaikh M. Charlson comorbidity index predicts chronic rather than acute radiation therapy induced toxicity in men with prostate cancer. Journal of Urology 2019; 201(4):e1058.
Journal of Urology
INTRODUCTION AND OBJECTIVES: The association between baseline comorbidities and the severity of radiotherapy (RT) adverse events is not well-established for prostate cancer (PCa). We explored the impact of Charlson Comorbidity Index (CCI) on the acute and chronic toxicities and survival in localized PCa managed by RT. METHODS: We included intermediate and high risk PCa treated by definitive RT between 1/2007 and 12/2012. Groups were created according to baseline CCI score into no, mild and severe comorbidity (CCI-0, 1 or 2+). Acute (during RT) and chronic (>3 months post-RT) RT-induced toxicities were graded based on RTOG/CTCAE criteria by reviewing follow up records. The groups were then compared based on patients' characteristics and treatment details. Correlation between comorbidities and acute/chronic toxicity was studied using Pearson Chi-square. Kaplan-Meier curves as well as uni/multi-variate analysis (MVA) were used to examine the impact of CCI groups on overall (OS) and disease specific (DSS) survival. RESULTS: 257 patients were identified after excluding low risk and prostatectomy cases. Median age was 73 years (48-85), 53% were African American and 67% were of intermediate risk. Median RT dose was 76 Gy and 47% received androgen deprivation therapy. CCI groups 0, 1 and 2+ encompassed 76 (30%), 54 (21%) and 127 (49%) patients, respectively. Groups were generally well-balanced. After a median follow-up of 92 months (2-135); 28% and 41% developed at least a single grade 2 (G2+) acute and chronic RT toxicities. Acute and late genitourinary and lower gastrointestinal G2+ side effects occurred in (21% & 28% vs 8% & 7%; respectively). Although CCI group was not correlated with G2+ acute toxicity (CCI-0: 26%, CCI-1: 33% & CCI-2: 27%; p=0.62); late G2+ toxicities were significantly more common in CCI-2+ (47%) than in CCI-1 (44%) and CCI-0 (29%); p=0.032. Moreover, the occurrence of multiple late G2+ adverse events per patient was more with higher CCI (p<0.001). OS in 10 and 15 years was significantly different across CCI groups (76% & 53%, 46% & 31% and 55% & 14%, for CCI-0, 1 and 2+ respectively; p<0.001). CCI-0 had better DSS than CCI-2+ (p=0.03) with no difference for CCI-0 vs 1 (p = 0.1). On MVA, increased CCI was deterministic for OS (p<0.001) and was only marginal for DSS (p=0.05). CONCLUSIONS: Higher CCI was a significant predictor for more intense late radiotherapy induced toxicities in addition to shorter OS in PCa. Baseline comorbidities should be taken into consideration during patient counseling for treatment options and also in follow up visits for men with localized prostate cancer.