Prevention of thromboembolic events after radical prostatectomy in patients with hereditary thrombophilia due to a factor V Leiden mutation by multidisciplinary coagulation management

Objective:To examine the perioperative impact of factor V Leiden mutation on thromboembolic events'risk in radical prostatectomy(RP)patients.With an incidence of about 5%,factor V Leiden mutation is the most common hereditary hypercoagulability among Caucasians and rarer in Asia.The increased risk of thromboembolic events is three-to seven-fold in heterozygous and to 80-fold in homozygous patients.Methods:Within our prospectively collected database,we analysed 33006 prostate cancer patients treated with RP between December 2001 and December 2020.Of those,patients with factor V Leiden mutation were identified.All patients received individualised recommendation of haemostaseologists for perioperative anticoagulation.Thromboembolic complications(deep vein thrombosis and pulmonary embolism)were assessed during hospital stay,as well as according to patient reported outcomes within the first 3 months after RP.Results:Overall,85(0.3%)patients with known factor V Leiden mutation were identified.Median age was 65(interquartile range:61-68)years.There was at least one thrombosis in 53(62.4%)patients and 31(36.5%)patients had at least one embolic event in their medical history before RP.Within all 85 patients with factor V Leiden mutation,we experienced no thromboembolic complications within the first 3 months after surgery.Conclusion:In our cohort of patients with factor V Leiden mutation,no thromboembolic events were observed after RP with an individualised perioperative coagulation management concept.This may reassure patients with this hereditary condition who are counselled for RP.

Reduced anoctamin 7(ANO7) expression is a strong and independent predictor of poor prognosis in prostate cancer

Objective:Anoctamin 7(ANO7)is a calcium2+-dependent chloride ion channel protein.Its expression is restricted to prostate epithelial cells.The exact function is unknown.This study aimed to analyze ANO7 expression and its clinical significance in prostate cancer(PCa).Methods:ANO7 expression was assessed by immunohistochemistry in 17,747 clinical PCa specimens.Results:ANO7 was strongly expressed in normal prostate glandular cells but often less abundant in cancer cells.ANO7 staining was interpretable in 13,594 cancer tissues and considered strong in 34.4%,moderate in 48.7%,weak in 9.3%,and negative in 7.6%.Reduced staining was tightly linked to adverse tumor features[high classical and quantitative Gleason grade,lymph node metastasis,advanced tumor stage,high Ki67 labeling index,positive surgical margin,and early biochemical recurrence(P<0.0001 each)].The univariate Cox hazard ratio for prostate-specific antigen(PSA)recurrence after prostatectomy in patients with negative vs.strong ANO7 expression was 2.98(95%confidence interval 2.61–3.38).The prognostic impact was independent of established pre-or postoperatively available parameters(P<0.0001).Analysis of annotated molecular data showed that low ANO7 expression was linked to TMPRSS2:ERG fusions(P<0.0001),elevated androgen receptor expression(P<0.0001),as well as presence of 9 of 11 chromosomal deletions(P<0.05 each).A particularly strong association of low ANO7 expression with phosphatase and tensin homolog(PTEN)deletion may indicate a functional relationship with the PTEN/AKT pathway.Conclusions:These data identify reduced ANO7 protein expression as a strong and independent predictor of poor prognosis in PCa.ANO7 measurement,either alone or in combination,might provide clinically useful prognostic information in PCa.

Loss of PSP94 expression is associated with early PSA recurrence and deteriorates outcome of PTEN deleted prostate cancers

Objective: Prostate secretory protein of 94 amino acids(PSP94) is a target gene of the EZH2 transcriptional repressor and is often downregulated in prostate cancer;however, its prognostic value is disputed.Methods: Immunohistochemical analysis of a tissue microarray of 12, 432 prostate cancer specimens was performed to evaluate PSP94 expression. Correlation of PSP94 expression with tumor phenotype, patient prognosis, TMPRSS2:ERG fusion status, EZH2 expression and PTEN deletion was studied.Results: PSP94 expression was increased in benign prostatic hyperplasia;however, it was downregulated in 48% and negative in42% of the 9, 881 interpretable prostate cancer specimens. The loss of PSP94 expression was inversely correlated to EZH2 expression(P < 0.0001) and largely unrelated to the ERG status, but strongly correlated with high Gleason grade, advanced tumor stage, and nodal metastasis(P <0.0001 each). The fraction of PSP94-negative cancer specimens increased from 40% in pT2 to 52%in pT3 b-pT4(P < 0.0001) and from 40% in Gleason 3+3 = 6 to 46% in Gleason 4+3 = 7 and 60% in Gleason ≥4+4 = 8(P <0.0001). Loss of PSP94 was linked to early prostate-specific antigen recurrence, but with little absolute effect(P < 0.0001).However, it provided additional prognostic impact in cancer specimens with PTEN deletion. Loss of PSP94 deteriorated prognosis of cancer patients with PTEN deletion by more than 10%(P < 0.0001). The combination of PTEN deletion and PSP94 loss provided independent prognostic information that was observed in several subgroups defined by classical and quantitative Gleason grade.Conclusions: The results of our study suggest that combined PSP94/PTEN analysis can be potentially used in the clinical prognosis of prostate cancer.

Cytoreductive radical prostatectomy after chemohormonal therapy in patients with primary metastatic prostate cancer

Objective:Cytoreductive radical prostatectomy(cRP)has been proposed as local treatment option in metastatic hormone-sensitive prostate cancer(mHSPC)to prevent local complications and potentially improve oncological outcomes.In this study,we examined the feasibility of a multimodal concept with primary chemohormonal therapy followed by cRP and analyzed prostate size reduction under systemic treatment,postoperative complication rates,as well as early postoperative continence.Methods:In this retrospective study,38 patients with mHSPC underwent cRP after primary chemohormonal therapy(3-monthly luteinising hormone-releasing hormone-analogue+six cycles 3-weekly docetaxel 75 mg/m2)at two centers between September 2015 and December 2018.Results:Overall,10(26%)patients had high volume and 28(74%)patients had low volume disease at diagnosis,according to CHAARTED definition.Median prostate-specific antigen(PSA)decreased from 65 ng/mL(interquartile range[IQR]35.0-124.5 ng/mL)pre-chemotherapy to 1 ng/mL(IQR 0.3-1.7 ng/mL)post-chemotherapy.Prostate gland volume was significantly reduced by a median of 50%(IQR 29%-56%)under chemohormonal therapy(p=0.003).Postoperative histopathology showed seminal vesicle invasion in 33(87%)patients and negative surgical margins in 17(45%)patients.Severe complications(Grade 3 according to Clavien-Dindo)were observed in 4(11%)patients within 30 days.Continence was reached in 87%of patients after 1 month and in 92%of patients after 6 months.Median time to castration-resistance from begin of chemohormonal therapy was 41.1 months and from cRP was 35.9 months.Postoperative PSA-nadir≤1 ng/mL versus>1 ng/mL was a significant predictor of time to castration-resistance after cRP(median not reached versus 5.3 months;p<0.0001).Conclusion:We observed a reduction of prostate volume under chemohormonal therapy going along with a low postoperative complication and high early continence rate.However,the oncologic benefit from cRP is still under evaluation.

Differences in rates of pelvic lymph node dissection in National Comprehensive Cancer Network favorable,unfavorable intermediate-and high-risk prostate cancer across United States SEER registries

Background:The National Comprehensive Cancer Network(NCCN)guidelines recommend pelvic lymph node dissection(PLND)in NCCN high-and intermediate-risk prostate cancer patients.We tested for PLND nonadherence(no-PLND)rates within the Surveillance Epidemiology and End Results(2010-2015).Materials and methods:We identified all radical prostatectomy patients who fulfilled the NCCN PLND guideline criteria(n=23,495).Nonadherence rates to PLND were tabulated and further stratified according to NCCN risk subgroups,race/ethnicity,geographic distribution,and year of diagnosis.Results:Overall,the no-PLND rate was 26%;it was 41%,25%,and 11%in the NCCN intermediate favorable,intermediate unfavorable,and high-risk prostate cancer patients,respectively(p<0.001).Overtime,the no-PLND rates declined in the overall cohort and within each NCCN risk subgroup.Georgia exhibited the highest no-PLND rate(49%),whereas New Jersey exhibited the lowest(15%).Finally,no-PLND race/ethnicity differences were recorded only in the NCCN intermediate unfavorable subgroup,where Asians exhibited the lowest no-PLND rate(20%)versus African Americans(27%)versus Whites(26%)versus Hispanic-Latinos(25%).Conclusions:The lowest no-PLND rates were recorded in the NCCN high-risk patients followed by NCCN intermediate unfavorable and favorable risk in that order.Our findings suggest that unexpectedly elevated differences in no-PLND rates warrant further examination.In all the NCCN risk subgroups,the no-PLND rates decreased over time.