Experimental Study On Targeted Therapy Of ¹²⁵I Labeled Oncolytic Adenovirus On Prostate Cancer Cells And Clinical Effect Of External Radiation Combined With Endocrine Therapy On Biochemical Recurrence Of Prostate Cancer

Objective Prostate cancer is the most common cancer among men.It is the most common male malignancy in the developed world.In recent years,the incidence of prostate cancer in China has been increasing significantly,and it has become a urinary malignancy seriously affecting the health of men in China.Prostate cancer is usually diagnosed after appearance of symptoms,changing from locally advanced or metastatic to symptomatic disease with an ove rall 5-year survival rate of 70%.In this study,we explored the inhibitory effect of radionuclide ¹²⁵I labeled tumor-specific oncolytic adenovirus on prostate cancer cells,so as to find an effective treatment for prostate cancer.At the same time,biochemical recurrence of prostate cancer usually occurs after radical prostatectomy.In this study,we analyzed the therapeutic effect of external irradiation combined with endocrine therapy on postoperative biochemical recurrence of prostate cancer.Methods Part Ⅰ:the oncolytic adenovirus labeled with ¹²⁵I was constructed by PCR amplification and double enzyme cleavage ligation technique,and the killing effect of ¹²⁵I oncolytic adenovirus on prostate cancer cells was detected by flow cytometry in vivo and in vitro.Part Ⅱ:Analyzing retrospectively 132 patients with biochemical recurrence of prostate cancer who underwent radical prostatectomy in the urological department of Xuzhou Central Hospital of Jiangsu Province on January 1,2010 to December 31,2018.According to the different treatment regimen after biochemical relapse,36 cases were divided into external radiotherapy alone group,45 cases were endocrine therapy alone group and 51 cases were combined with external radiotherapy endocrine therapy group.Collecting clinical data,body mass index,Gleason score,pathological stage,positive margin,lymph node and distant metastasis,preoperative PSA（prostate specific antigen）value,incidence of adverse reactions after treatment,and tumor specific survival time of patients in different groups.Results Part Ⅰ:¹²⁵I-oncolytic adenovirus could significantly induce tumor cell apoptosis in vivo and in vitro,and the inhibition rate was significantly higher than that of ¹²⁵I group and virus complex group（unlabeled）（t=-5.252-4.962,P<0.05,t=2.9912.847,P<0.05）.Part Ⅱ:The tumor-specific survival rates of the endocrine therapy group and the external radiation therapy group were 63.2%,44.16%and 50.85%,respectively,and the tumor-specific survival times of the endocrine therapy group were 77.47±7.84months,52.49±4.62 months and 60.80±6.98 months,respectively.The 5-year tumor-specific survival rate in the combination therapy group was significantly different from that of external radiation alone and endocrine alone（P<0.05）.Cox regression analysis showed that the treatment method（HR:0.41,95%CI:0.21-0.76;P=0.015）,preoperative PSA value（HR:4.21,95%,CI:3.70-4.78;P=0.035）,Gleason score（HR:3.19,95%CI:2.32-4.19;P=0.037）,lymphatic metastasis（HR:1.54,95%CI:1.02-3.15;P=0.035）was an independent factor affecting the 5-year tumor-specific survival rate of patients with biochemical recurrence of prostate cancer.Meanwhile,there was no significant difference in the incidence of adverse reactions such as hot flash reaction,urethral reaction,intestinal reaction and sexual dysfunction between groups（P>0.05）.Conclusion Targeting effect of oncolytic adenovirus ¹²⁵I on prostate cancer can significantly kill prostate cancer cells,reduce cancer tissue weight and angiogenesis,and improve the tumor microenvironment.For patients with biochemical recurrence after radical prostatectomy,external radiation therapy combined with endocrine therapy has an advantage in prolonging tumor-specific survival,was no significant difference in adverse reactions with other treatment groups.Overall,it is more likely to strike a balance between survival benefits and safety of treatment.