^(68)Ga-PSMA ligand PET/CT integrating indocyanine green-guided salvage lymph node dissection for lymph node metastasis after radical prostatectomy

To efficiently remove all recurrent lymph nodes(rLNs)and minimize complications,we developed a combination approach that consisted of ^(68)Gallium prostate-specific membrane antigen(PSMA)ligand positron emission tomography(PET)/computed tomography(CT)and integrated indocyanine green(ICG)-guided salvage lymph node dissection(sLND)for rLNs after radical prostatectomy(RP).Nineteen patients were enrolled to receive such treatment.^(68)Ga-PSMA ligand PET/CT was used to identify rLNs,and 5 mg of ICG was injected into the space between the rectum and bladder before surgery.Fluorescent laparoscopy was used to perform sLND.While extensive LN dissection was performed at level I,another 5 mg of ICG was injected via the intravenous route to intensify the fluorescent signal,and laparoscopy was introduced to intensively target stained LNs along levels I and II,specifically around suspicious LNs,with ^(68)Ga-PSMA ligand PET/CT.Next,both lateral peritonea were exposed longitudinally to facilitate the removal of fluorescently stained LNs at levels III and IV.In total,pathological analysis confirmed that 42 nodes were rLNs.Among 145 positive LNs stained with ICG,24 suspicious LNs identified with ^(68)Ga-PSMA ligand PET/CT were included.The sensitivity and specificity of ^(68)Ga-PSMA ligand PET/CT for detecting rLNs were 42.9%and 96.6%,respectively.For ICG,the sensitivity was 92.8%and the specificity was 39.1%.At a median follow-up of 15(interquartile range[IQR]:6–31)months,15 patients experienced complete biochemical remission(BR,prostate-specific antigen[PSA]<0.2 ng ml−1),and 4 patients had a decline in the PSA level,but it remained>0.2 ng ml−1.Therefore,^(68)Ga-PSMA ligand PET/CT integrating ICG-guided sLND provides efficient sLND with few complications for patients with rLNs after RP.

Combined analysis of CRMP4 methylation levels and CAPRA-S score predicts metastasis and outcomes in prostate cancer patients

The present study analyzed the predictive value of combined analysis of collapsin response mediator protein 4 （CRMP4） methylation levels and the Cancer of the Prostate Risk Assessment （CAPRA-S） Postsurgical score of patients who required adjuvant hormone therapy （AHT） after radical prostatectomy （RP）, We retrospectively analyzed 305 patients with prostate cancer （PCa） who received RP and subsequent androgen deprivation therapy （ADT）. Two hundred and thirty patients with clinically high-risk PCa underwent immediate ADT, and 75 patients with intermediate risk PCa underwent deferred ADT. CRMP4 methylation levels in biopsies were determined, and CAPRA-S scores were calculated. In the deferred ADT group, the values of the hazard ratios for tumor progression and cancer-specific mortality （CSM） in patients with 〉15% CRMP4 methylation were 6.81 （95% CI, 2.34-19.80） and 12.83 （95% CI. 2.16-26.10）, respectively. Receiver-operating characteristic curve analysis indicated that CRMP4 methylation levels 〉15% served as a significant prognostic marker of tumor progression and CSM. In the immediate ADT group, CAPRA-S scores ：〉6 and CRMP4 methylation levels ：〉15% were independent predictors of these outcomes （uni- and multi-variable Cox regression analyses）. The differences in the 5-year progression-free survival between each combination were statistically significant. Combining CAPRA-S score and CRMP4 methylation levels improved the area under the curve compared with the CRMP4 or CAPRA-S model. Therefore, CRMP4 methylation levels ：〉15% were significantly associated with a poor prognosis and their combination with CAPRA-S score accurately predicted tumor progression and metastasis for patients requiring AHT after RP.

Coexpression of TLR9 and VEGF-C is associated with lymphatic metastasis in prostate cancer

Prostate cancer(PCa)is one of the most frequent cancers in men,and its biomolecular targets have been extensively studied.This study aimed to analyze the expression of toll-like receptor 9(TLR9)and vascular endothelial growth factor C(VEGF-C)and the clinical value of the coexpression of TLR9 and VEGF-C in PCa.We retrospectively evaluated 55 patients with clinically localized,intermediate-risk,or high-risk PCa who underwent laparoscopic radical prostatectomy(LRP)and extended pelvic lymph node dissection(ePLND)without neoadjuvant hormonal therapy at a single institution from June 2013 to December 2016.In all 55 patients,the median number of lymph nodes(LNs)resected was 23(range:18-31),and a total of 1269 LNs were removed,of which 78 LNs were positive.Seventeen patients had positive LNs,with a positive rate of 30.9%.In addition,the immunohistochemical results in the above patients revealed that high TLR9 expression was correlated with higher Gleason score(GS)(P=0.049),increased LN metastasis(P=0.004),and more perineural invasion(PNI)(P=0.033).Moreover,VEGF-C expression was associated with GS(P=0.040),pathological stage(pT stage)(P=0.022),LN metastasis(P=0.003),and PNI(P=0.001).Furthermore,a significant positive correlation between TLR9 and VEGF-C was found(P<0.001),and the TLR9/VEGF-C phenotype was associated with LN metastasis(P=0.047).Collectively,we propose that TLR9 stimulation may promote LN metastasis in PCa cells through the upregulation of VEGF-C expression,thereby affecting the prognosis of PCa patients.Therefore,these markers may serve as valuable targets for the treatment of PCa.