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.

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.

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.

Multimodal therapy in oligometastatic prostate cancer: A glimpse into the future?

Dear editor,Since the introduction of radiotracer-labeled prostatespecific membrane antigen(PSMA)targeting positron emission tomography(PET),imaging of prostate cancer(PCa)improved drastically[1,2].Subsequently,metastases may be detected in earlier stages with possible implications on treatment planning[3].Here,we described the multimodal treatment approach on a young patient with newly diagnosed metastatic PCa conducted according to the results of repeated PSMAePET imaging.

Cardiac Structure and Function in Men with Prostate Cancer Receiving Androgen-Deprivation Therapy and the Effects of Recreational Small-Sided Football Training:A Randomized Controlled Trial

Purpose: Androgen deprivation therapy (ADT) is a cornerstone in prostate cancer (PCa) management that prolongs PCa-free and overall survival, but effects of ADT on human cardiac function have not been investigated. We used echocardiography to examine cardiac structure and function in patients with prostate cancer receiving ADT and to determine whether an exercise intervention can elicit cardiac adaptations in these subjects. Methods: Forty-three patients with prostate cancer receiving ADT were randomized to 12 weeks football training (ST group;n = 20) or usual care (control [CO] group;n = 23). Cardiac function was assessed at baseline and after 12 weeks by comprehensive echocardiography. Peak oxygen consumption, blood pressure and peripheral microvascular function was also measured. Results: At baseline, no considerable echocardiographic abnormalities were observed. In the ST group, increases in left ventricular diastolic function variables including E/A ratio (P = 0.03), E’ (P = 0.016), E’TDIcolor (P = 0.040) and in left atrial diameter (P = 0.001) were observed after 12 weeks. In addition, diastolic blood pressure (P = 0.027) and resting heart rate (P 0.001) were reduced after ST. In the CO group, no significant changes were observed in the examined variables after 12 weeks. Despite within group changes in the ST group, no significant differences were observed after 12 weeks between groups in echocardiographic variables, peak oxygen consumption, blood pressure and peripheral microvascular function. Conclusion: In men with prostate cancer receiving ADT, echocardiography showed no abnormalities in cardiac structure and function. Twelve weeks of ST failed to elicit significant cardiovascular adaptations and ADT may blunt cardiovascular adaptations to short-term exercise training.

Apalutamide for metastatic castration-sensitive prostate cancer:final analysis of the Asian subpopulation in the TITAN trial

The final analysis of the phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen(TITAN)trial showed improvement in overall survival(OS)and other efficacy endpoints with apalutamide plus androgen deprivation therapy(ADT)versus ADT alone in patients with metastatic castration-sensitive prostate cancer(mCSPC).As ethnicity and regional differences may affect treatment outcomes in advanced prostate cancer,a post hoc final analysis was conducted to assess the efficacy and safety of apalutamide in the Asian subpopulation.Event-driven endpoints were OS,and time from randomization to initiation of castration resistance,prostate-specific antigen(PSA)progression,and second progression-free survival(PFS2)on first subsequent therapy or death.Efficacy endpoints were assessed using the Kaplan–Meier method and Cox proportional-hazards models without formal statistical testing and adjustment for multiplicity.Participating Asian patients received once-daily apalutamide 240 mg(n=111)or placebo(n=110)plus ADT.After a median follow-up of 42.5 months and despite crossover of 47 placebo recipients to open-label apalutamide,apalutamide reduced the risk of death by 32%(hazard ratio[HR]:0.68;95%confidence interval[CI]:0.42–1.13),risk of castration resistance by 69%(HR:0.31;95%CI:0.21–0.46),PSA progression by 79%(HR:0.21;95%CI:0.13–0.35)and PFS2 by 24%(HR:0.76;95%CI:0.44–1.29)relative to placebo.The outcomes were comparable between subgroups with low-and high-volume disease at baseline.No new safety issues were identified.Apalutamide provides valuable clinical benefits to Asian patients with mCSPC,with an efficacy and safety profile consistent with that in the overall patient population.

Comparison of survival outcomes between laparoscopic versus open radical nephroureterectomy in upper tract urothelial cancer patients:Experiences of a tertiary care single center

Objectives:To test for differences in overall and recurrence-free survival between laparoscopic and open surgical approaches in patients undergoing radical nephroureterectomy(RNU)for upper tract urothelial carcinoma(UTUC).Materials and methods:We retrospectively identified patients treated for UTUC from 2010 to 2020 from our institutional database.Patients undergoing laparoscopic or open RNU with no suspicion of metastasis(cM0)were for the current study population.Patients with suspected metastases at diagnosis(cM1)or those undergoing other surgical treatments were excluded.Tabulation was performed according to the laparoscopic versus open surgical approach.Kaplan-Meier plots were used to test for differences in overall and recurrence-free survival with regard to the surgical approach.Furthermore,separate Kaplan-Meier plots were used to test the effect of preoperative ureterorenoscopy on overall and recurrence-free survival within the overall study cohort.Results:Of the 59 patients who underwent nephroureterectomy,29%(n=17)underwent laparoscopic nephroureterectomy,whereas 71%(n=42)underwent open nephroureterectomy.Patient and tumor characteristics were comparable between groups(p≥0.2).The median overall survival was 93 and 73 months in the laparoscopic nephroureterectomy group compared to the open nephroureterectomy group(p=0.5),respectively.The median recurrence-free survival did not differ between open and laparoscopic nephroureterectomies(73 months for both groups;p=0.9).Furthermore,the median overall and recurrence-free survival rates did not differ between patients treated with and without preoperative ureterorenoscopy.Conclusions:The results of this retrospective,single-center institution showed that overall and recurrence-free survival rates did not differ between patients with UTUC treated with laparoscopic and open RNU.Furthermore,preoperative ureterorenoscopy before RNU was not associated with higher overall or recurrence-free survival rates.

HoLEP does not affect the overall sexual function of BPH patients： a prospective study

We aimed to prospectively evaluate the influence of holmium laser enucleation of the prostate （HoLEP） on the overall postoperative sexual function of benign prostatic hyperplasia （BPH） patients with lower urinary tract symptoms （LUTS） and to explore the relationship between sexual function and LUTS. From January 2010 to December 2011, sixty sexually active consecutive patients with BPH who underwent HoLEP were prospectively enrolled in the study. All patients filled out the Male Sexual Health Questionnaire （MSHQ） for evaluation of their overall sexual function and the International Prostatic Symptom Score （IPSS） for pre- and post-operative 6 months evaluation of their voiding symptoms. The LUTS and sexual function changes were statistically analyzed. The preoperative and 6 months postoperative status of the patients was compared using uroflowmetry and IPSS questionnaires. The analysis revealed significant improvements following HoLEP. Among the sub-domains of the MSHQ, postoperative sexual function, including erection, ejaculation, sexual satisfaction, anxiety or sexual desire, did not significantly change after HoLEP （P 〉 0.05）, whereas satisfaction scores decreased slightly due to retrograde ejaculation in 38 patients （63.3%）. Sexual satisfaction improved significantly and was correlated with the improvements of all LUTS and the quality-of-life （QoL） domains in IPSS after surgery （QoL; relative risk [RR]： -0.293; total symptoms, RR： -0.411; P 〈 0.05）. The nocturia score was associated with the erectile function score （odds ratio 0.318, P = 0.029）. The change in ejaculatory scores did not show significant association with IPSS scores. HoLEP did not influence overall sexual function, including erectile function. In addition, sexual satisfaction improved in proportion with the improvement of LUTS.

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.

Radical prostatectomy in patients aged 75 years or older:review of the literature

Given the demographic trends toward a considerably longer life expectancy,the percentage of elderly patients with prostate cancer will increase further in the upcoming decades.Therefore,the question arises,should patients ≥75 years old be offered radical prostatectomy and under which circumstances? For treatment decision-making,life expectancy is more important than biological age.As a result,a patient's health and mental status has to be determined and radical treatment should only be offered to those who are fit.As perioperative morbidity and mortality in these patients is increased relative to younger patients,patient selection according to comorbidities is a key issue that needs to be addressed.It is known from the literature that elderly men show notably worse tumor characteristics,leading to worse oncologic outcomes after treatment.Moreover,elderly patients also demonstrate worse postoperative recovery of continence and erectile function.As the absolute rates of both oncological and functional outcomes are still very reasonable in patients ≥75 years,a radical prostatectomy can be offered to highly selected and healthy elderly patients. Nevertheless,patients clearly need to be informed about the worse outcomes and higher perioperative risks compared to younger patients.