| Objective(s):To compare the actual efficacy and safety of different combination therapies in the treatment of metastatic hormone-sensitive prostate cancer with high-volume disease,explore the factors influencing disease progression in this patient population,and provide reference for clinical physicians in selecting specific treatment plans.Methods:According to the CHAARTED criteria,a retrospective analysis was conducted on the clinical data of 248 patients diagnosed with high-volume disease metastatic hormone-sensitive prostate cancer(m HSPC)in Yunnan Cancer Hospital from January 2017 to January 2022.The clinical pathological data included age,TNM stage,Gleason score,testosterone at initial diagnosis,Eastern Cooperative Oncology Group performance status(ECOG PS),prostate-specific antigen(PSA),albumin,globulin,lactate dehydrogenase(LDH),alkaline phosphatase(ALP),lymphocytes,monocytes,neutrophils,platelets,CD4~+/CD8~+ratio,and imaging data such as B-ultrasound,CT,PET-CT,MRI and whole-body bone scan.According to the treatment plan,the patients were divided into three groups:the Bicalutamide(Bic)group,the abiraterone acetate(AA)group,and the Docetaxel(Doc)group.The primary efficacy indicator was progression-free survival(PFS),and the secondary efficacy indicators were PSA response rate,PSA response rate within 6 months,PSA response rate between 6 and 12 months,nadir PSA(n PSA),time to PSA nadir(TTN),and adverse reactions to the drugs.Statistical analysis was performed using SPSS26.0software,and the Kaplan-Meier survival analysis,Log-Rank test,Kruskal-Wallis H test,and chi-square test were used to compare the differences in the primary and secondary efficacy indicators among the three combination therapies.The survival curves of the three groups were plotted using R(version 4.2.2),and the Cox proportional hazards model was used for univariate and multivariate regression analyses to explore the factors influencing disease progression.The survival curves of the three groups were plotted using multivariate Cox regression analysis,and the efficacy differences among the three combination therapies were further compared.Results:1.A total of 248 m HSPC patients with high-volume disease were included in this study,including 100 in the Bic group,78 in the Doc group,and 70 in the AA group.2.The statistical analysis showed that there was a statistical difference in age and albumin to globulin ratio(AGR)before diagnosis among the three groups(P<0.05),while the distribution of other baseline data was not statistically different(P>0.05).Therefore,the baseline data of patients in different combination therapy groups were basically balanced and comparable.3.All 248 cases were closely followed up for a period of 3.9 to 50.6 months,with a median follow-up time of 32.5months.The median PFS differences among the three groups were statistically significant(P<0.001).Compared with the Bic group,the median PFS in the Doc group was prolonged by 9.1 months(20.8 months vs.11.7 months,P<0.001),and in the AA group,it was prolonged by 14.3 months(26.0 months vs.11.7 months,P<0.001).The median PFS in the AA group was 5.2 months longer than that in the Doc group(26.0 months vs.20.8 months,P=0.009).4.The 1-year,2-year,and 3-year PFS rates in the AA and Doc groups were significantly higher than those in the Bic group.The 1-year PFS rate in the AA group was comparable to that in the Doc group,while the 2-year and 3-year PFS rates in the AA group were significantly higher than those in the Doc group.5.The median n PSA in the Bic group was the highest(0.69ng/ml),followed by the Doc group(0.15 ng/ml),and the AA group was the lowest(0.09 ng/ml).The difference among the three groups was statistically significant(P<0.001).The comparison between any two groups showed a statistically significant difference between the AA group and the Bic group(P<0.001),while there was no statistical difference between other groups(P>0.05).6.The median TTN in group AA(10.4 months)was significantly longer than that in group Bic(7.75 months)and group Doc(9 months),and the difference among the three groups was statistically significant(P<0.001).Pairwise comparison showed that there was a statistically significant difference between group AA and group Bic,as well as group AA and group Doc(P<0.05),while there was no statistically significant difference between group Bic and group Doc(P=0.114).7.The PSA response rates of group Doc and group AA were 56.41%and 62.86%,respectively,both significantly higher than that of group Bic(34%),and the difference among the three groups was statistically significant(P<0.001).Pairwise comparison showed that there was a statistically significant difference between group Bic and group Doc,as well as group Bic and group AA(P<0.05),while there was no statistically significant difference between group Doc and group AA(P=0.425).8.The rates of PSA response within 6 months after treatment in the Bic group,Doc group,and AA group were 21%,32.05%and38.57%(P=0.039),respectively.Pairwise comparison showed a statistically significant difference between the Bic group and AA group(P=0.012),while no statistically significant difference was found between the Doc group and the Bic group or AA group(P>0.05).9.The rates of PSA response within 6～12 months after treatment in the Bic group,Doc group,and AA group were 10%,16.67%,and 24.29%(P=0.044),respectively.Pairwise comparison showed a statistically significant difference between the Bic group and AA group(P=0.012),while no statistically significant difference was found between the Doc group and the Bic group or AA group(P>0.05).10.The incidence of grade 3～4 adverse reactions was highest in the Doc group(21.79%),followed by the AA group(12.86%),and lowest in the Bic group(10%).However,there was no statistically significant difference among the three groups of patients(P=0.077),and no deaths occurred due to adverse reactions in any of the patients.11.Univariate analysis found that the M stage,initial PSA value,PSA response,PSA response within 6 months,TTN,treatment regimen,whether LDH was elevated,platelet-to-lymphocyte ratio(PLR),and initial testosterone value were associated with progression-free survival.12.Multivariate Cox regression analysis showed that the M stage,PSA response,PSA response within 6 months,TTN,and treatment regimen had a statistically significant impact on patient prognosis(P<0.05),and M1c stage,PSA non-response(PSA not dropping below 0.2 ng/ml),PSA non-response within 6 months,and TTN≤8.4 months were independent risk factors for disease progression in patients with high-volume disease m HSPC.13.The results of the multivariate Cox regression analysis showed that the median PFS in group Doc was significantly longer than that in group Bic(HR=0.493,95.0%CI:0.351～0.693,P<0.001),and the median PFS in group AA was significantly longer than that in group Bic(HR=0.340,95.0%CI:0.219～0.529,P<0.001),the median PFS in group AA was longer than that in group Doc(HR=0.690,95.0%CI:0.441～0.908,P=0.045).Conclusion(s):1.Compared with the treatment of castration combined with bicalutamide,the combination of castration and abiraterone or castration and docetaxel chemotherapy can significantly prolong the median PFS of patients with high-volume disease m HSPC.Based on the treatment of drug castration,the combination of abiraterone therapy prolongs the median PFS of patients with high-volume disease m HSPC more than the combination of docetaxel chemotherapy.2.The incidence of grade 3～4 adverse reactions is highest in the docetaxel group,followed by the abiraterone group,and lowest in the bicalutamide group,but there is no statistical difference between the three groups,and the adverse reactions of the three combination therapies are generally controllable.3.M1c stage,PSA non-response(PSA not decreased to below 0.2ng/ml),PSA non-response within 6 months,and TTN≤8.4 months are independent risk factors for disease progression in high-volume disease m HSPC patients. |
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