Prostate Index Research Articles

Functional outcome after radical prostatectomy in 1313 patients: A single-center study.

To assess the impact of urinary continence and erectile function on the quality of life in men undergoing radical prostatectomy (RP) for prostate cancer (PC), we analyzed the preoperative and 1-year postoperative outcomes of five functional domains and their influencing factors. In this prospective study, all patients undergoing open or robot-assisted RP between Febuary 2017 and March 2020 in a single academic center were included. Patient-reported outcomes were assessed pre- and 12 months postoperatively using the Expanded Prostate Index Composite (EPIC-26) survey, evaluating continence, irritative/obstructive micturition, gastrointestinal symptoms, sexuality, and overall vitality. We examined the impact of RP on sexual function and urinary continence using multivariable logistic regression models, accounting for patient and tumor characteristics. Overall, 1313 consecutive patients gave consent for study participation and completed both surveys. The median age was 66 years (IQR: 60-70). The majority of patients (n = 601, 46%) had an intermediate risk PC. Robotic RP was performed in 71.6% and nerve-sparing technique in 81% of the cases. The median pre- versus postoperative scores were the following: urinary continence 100 (IQR:91.8-100) versus 85.5 (64.8-100), irritative micturition 87.5 (IQR: 75-100) versus 93.8 (IQR: 87.5-100), gastrointestinal symptoms the same with 100 (IQR: 95.8-100), vitality 95 (IQR: 80-100) versus 90 (IQR: 75-100), and erectile function 65.3 (IQR: 38.8-87.5) versus 22.2 (IQR: 12.5-48.7), respectively. Age (p < 0.001), risk classification (p = 0.002), and nerve-sparing surgery (p = 0.016) were associated with good sexual function (EPIC-26 score ≥60), while only age (p = 0.001) was statistically significantly associated with good urinary continence (EPIC-26 score ≥80). Non-modifiable factors such as age and PC risk classification impact urinary continence and sexual function after RP. Nevertheless, urologic surgeons should further focus on improving nerve-sparing techniques, the only modifiable variable, to reduce the surgery's negative impact on urinary continence and sexual function.

Deciphering anti–benign prostatic hyperplasia potential of liangwanoside II based on metabolite profile characterization combined with targeted network pharmacology

Ethnopharmacological relevanceMetapanax delavayi (Franch.) J.Wen & Frodin (Araliaceae), known as “liang wang cha” in China, has been used to treat prostatitis as herbal tea in folk. Recent research suggested that aqueous extract of Metapanax delavayi leaves showed an advantage in anti–benign prostate hyperplasia (BPH) activity, and liangwanoside II was the main component of the active fraction. However, the anti–BPH effect of liangwanosdie II remains to be revealed. Aim of the studyThis study aims to decipher anti–BPH potential of liangwanoside II. Materials and methodsThe anti–BPH effect was evaluated by testosterone propionate–induced BPH rats after oral administration of liangwanoside II at the doses of 30, 60 and 120 mg/kg in vivo. Then, the metabolites of liangwanoside II in rats were identified using ultra–performance liquid chromatography coupled with quadrupole tandem time–of–flight mass spectrometry (UPLC–Q–TOF–MS). Finally, the targeted network pharmacology combined with experimental verification were explored for the mechanism elucidation in vivo. ResultsLiangwanoside II exhibited an anti–BPH effect through reducing the weight of the prostate, prostate index and serum prostatic acid phosphatase level, and improving the prostate tissue morphology in BPH rats. Further, 16 metabolites of liangwanoside II in vivo were identified by UPLC–Q–TOF–MS analysis, in which the prototype compound and 4 metabolites, such as liangwanoside I and serratagenic acid could be absorbed in the plasma and then penetrate the blood–prostate barrier. Then, followed by the targeted network pharmacology and experimental verification, we found that liangwanoside II and its metabolites could jointly involve in the inhibition of the inflammation reaction and hormone imbalance, thus reducing oxidative stress damage, and restoring the balance between cell proliferation and apoptosis, which contributed to the anti–BPH effect of liangwanoside II. ConclusionThe anti–BPH potential of liangwanoside II was revealed using metabolite profile characterization combined with targeted network pharmacology, providing new insight into the development and utilization of liangwanoside II.

Traditional Chinese Medicine Danzhi qing'e decoction inhibits inflammation-associated prostatic hyperplasia via inactivation of ERK1/2 signal pathway.

Inflammation plays a critical role during benign prostatic hyperplasia (BPH) development. Danzhi qing'e (DZQE) decoction is a traditional Chinese medicine that has been widely used for estrogen and androgen-related diseases. However, its effect on inflammation-related BPH remains unclear. To investigate the effect of DZQE on inhibition of inflammation-related BPH, and further identify the possible mechanism involved. Experimental autoimmune prostatitis (EAP)-induced BPH was established and then 2.7g/kg of DZQE was administrated orally for 4 weeks. The prostate sizes, weights and prostate index (PI) values were recorded. Hematoxylin and eosin (H&E) was performed for pathological analyses. Macrophage infiltrate was evaluated by Immunohistochemical (IHC). The inflammatory cytokine levels were measured by Rt-PCR and ELISA methods. The phosphorylation of ERK1/2 was examined by Western blot. The expression differences of mRNA expressions between EAP-induced and oestrogen/testosterone (E2/T)-induced BPH was investigated by RNA sequencing analyses. In vitro, human prostatic epithelial BPH-1cells were stimulated with the conditioned medium from monocyte THP-1-derived M2 macrophages (M2CM), followed by treatment of Tanshinone IIA (Tan IIA), Bakuchiol (Ba), ERK1/2 antagonist PD98059 or ERK1/2 agonist C6-Ceramide. The ERK1/2 phosphorylation and cell proliferation were then detected by Western blotting and CCK8 assay. DZQE significantly inhibited the prostate enlargement and decreased PI value in EAP rats. Pathological analysis showed that DZQE alleviated prostate acinar epithelial cell proliferation by decreasing and reduction of CD68+ and CD206+ macrophage infiltration in the prostate. The levels of cytokines TNF-α, IL-1β, IL-17, MCP-1, TGF-β, and IgG in EAP rats' prostate or serum were significantly suppressed by DZQE as well. Moreover, mRNA sequencing data showed that the expressions of inflammation-related genes were elevated in EAP-induced BPH but not in E2/T-induced BPH. ERK1/2-related genes expression has been found in both E2/T and EAP-induced BPH. ERK1/2 is one of the core signal pathways involved in EAP-induced BPH, which was activated in EAP group but inactivated in DZQE group. In vitro, two active components of DZQE Tan IIA and Ba inhibited M2CM-induced BPH-1cell proliferation, similarly to ERK1/2 inhibitor PD98059 did. Meanwhile, Tan IIA and Ba inhibited M2CM-induced ERK1/2 signal activation in BPH-1cells. When re-activated the ERK1/2 by its activator C6-Ceramide, the inhibitory effects of Tan IIA and Ba on BPH-1cell proliferation were blocked. DZQE suppressed inflammation-associated BPH via regulation of ERK1/2 signal by Tan IIA and Ba.

Neferine attenuates development of testosterone-induced benign prostatic hyperplasia in mice by regulating androgen and TGF-β/Smad signaling pathways

Benign prostatic hyperplasia (BPH) is a common urinary disease among the elderly, characterized by abnormal prostatic cell proliferation. Neferine is a dibenzyl isoquinoline alkaloid extracted from Nelumbo nucifera and has antioxidant, anti-inflammatory and anti-prostate cancer effects. The beneficial therapeutic effects and mechanism of action of neferine in BPH remain unclear.A mouse model of BPH was generated by subcutaneous injection of 7.5 mg/kg testosterone propionate (TP) and 2 or 5 mg/kg neferine was given orally for 14 or 28 days. Pathological and morphological characteristics were evaluated. Prostate weight, prostate index (prostate/body weight ratio), expression of type Ⅱ 5α-reductase, androgen receptor (AR) and prostate specific antigen were all decreased in prostate tissue of BPH mice after administration of neferine. Neferine also downregulated the expression of pro-caspase-3, uncleaved PARP, TGF-β1, TGF-β receptor Ⅱ (TGFBR2), p-Smad2/3, N-cadherin and vimentin. Expression of E-cadherin, cleaved PARP and cleaved caspase-3 was increased by neferine treatment.1–100 μM neferine with 1 μM testosterone or 10 nM TGF-β1 were added to the culture medium of the normal human prostate stroma cell line, WPMY-1, for 24 h or 48 h. Neferine inhibited cell growth and production of reactive oxygen species (ROS) in testosterone-treated WPMY-1 cells and regulated the expression of androgen signaling pathway proteins and those related to epithelial-mesenchymal transition (EMT). Moreover, TGF-β1, TGFBR2 and p-Smad2/3, N-cadherin and vimentin expression were increased but E-cadherin was decreased after 24 h TGF-β1 treatment in WPMY-1 cells. Neferine reversed the effects of TGF-β1 treatment in WPMY-1 cells. Neferine appeared to suppress prostate growth by regulating the EMT, AR and TGF-β/Smad signaling pathways in the prostate and is suggested as a potential agent for BPH treatment.

Simvastatin ameliorates testosterone-induced prostatic hyperplasia in rats via modulating IGF-1/PI3K/AKT/FOXO signaling

Benign prostatic hyperplasia (BPH) is characterized by non-malignant enlargement of prostate cells causing many lower urinary tract symptoms. BPH pathogenesis includes androgens receptors signaling pathways, oxidative stress, apoptosis, and possibly changes in IGF-1/PI3K/AKT/FOXO pathway. Altogether, modulating IGF-1/PI3K/AKT/FOXO signaling along with regulating oxidative stress and apoptosis might preserve prostatic cells from increased proliferation. Beyond statins' common uses, they also have anti-inflammatory, antioxidant, and anti-tumor effects. This study aims to determine simvastatin's beneficial effect on testosterone-induced BPH. Rats were randomly allocated into four groups, 9 rats each. The control group received olive oil subcutaneously and distilled water orally for 30 consecutive days. The second group received simvastatin (20 mg/kg, p.o.) dissolved in distilled water. The BPH-induced group received testosterone enanthate (3 mg/kg, s.c.) dissolved in olive oil, and the BPH-induced treated group received both simvastatin and testosterone. Testosterone significantly increased prostate index and severity of histopathological alterations in prostate tissues as well as 5-alpha reductase enzyme level in contrast to simvastatin treatment that reversed the testosterone-induced alterations in these parameters. Likewise, testosterone up-regulated IGF-1/PI3K/AKT signaling pathway and down-regulated FOXO transcription factor. It also decreased apoptotic markers level in prostatic tissue BAX, caspase-3, and caspase-9, while it elevated Bcl-2 level. In addition, it alleviated reduced GSH and GPX5 levels and SOD activity. Simvastatin treatment significantly opposed testosterone's effect on all aforementioned parameters. In conclusion, this study demonstrates that simvastatin is a possible treatment for BPH which may be attributed to its effect on IGF-1/PI3K/AKT/FOXO signaling pathway as well as anti-oxidant and apoptotic effects.

Amelioration of chronic prostatitis by fractions of Mongolian medicine Hosta plantaginea flowers via inhibition of NF-κB, MAPKs, JAK-STAT, and PI3K-Akt signaling pathways in rats.

Hosta plantaginea (Lam.) Aschers flower is an important Mongolian medicine beneficial in the treatment of chronic prostatitis (CP) in the absence of scientific evidence. The aim of this study was to reveal the therapeutical effects and potential mechanisms of H. plantaginea flowers extract (HP) and its different polarity fractions (HPA∼D) on autoimmune CP (ACP) model rats. Sprague-Dawley male rats were randomly assigned to 13 groups (n=6/group). Except the sham group, all rats were injected with a mixture of prostate antigen and complete Freund's adjuvant on days 0, 7, and 21 to establish ACP model rats. Afterwards, ACP model rats were orally gavaged with HP or HPA∼D (1 and 4g/kg of raw herbal material) or positive drug (Prostat, 200mg/kg) daily from day 21 to day 50 for 30 days, while the sham and model groups were treated simultaneously with isopyknic of 0.3% sodium carboxymethyl cellulose. Histopathological analysis, biochemical parameters, and protein expression of prostate tissues were investigated. In comparison with the model group, all fraction groups experienced improved CP effects, including restored body weight, reduced prostate gland edema and prostate index, decreased prostatic leukocytes, increased prostatic lecithin bodies, and alleviated histopathological damage to prostate tissue. Furthermore, all fraction groups markedly inhibited the phosphorylated protein of nuclear factor kappa-B p65 (NF-κB p65), NF-κB inhibitor alpha (IκBα), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (Erk), just another kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), phosphoinositide 3-kinase (PI3K), and protein kinase B (Akt) than the model group. All fractions of HP exerted significant anti-CP effects by inhibiting NF-κB, MAPKs, JAK-STAT and PI3K-Akt pathways in ACP model rats. These findings provide scientific evidence that H. plantaginea flowers can be used as a pivotal Mongolian medicine in clinical applications for the treatment of CP.

MP54-06 EFFECT OF SMOKING ON PROSTATE CANCER SURVIVORS' FUNCTION AND QUALITY OF LIFE: AN ANALYSIS OF THE CEASAR (COMPARATIVE EFFECTIVENESS ANALYSIS OF SURGERY AND RADIATION) STUDY

You have accessJournal of UrologyCME1 Apr 2023MP54-06 EFFECT OF SMOKING ON PROSTATE CANCER SURVIVORS' FUNCTION AND QUALITY OF LIFE: AN ANALYSIS OF THE CEASAR (COMPARATIVE EFFECTIVENESS ANALYSIS OF SURGERY AND RADIATION) STUDY David-Dan Nguyen, Daniel A. Barocas, Li-Ching Huang, Zhiguo Zhao, Karen E. Hoffman, Tatsuki Koyama, David F. Penson, and Christopher J.D. Wallis David-Dan NguyenDavid-Dan Nguyen More articles by this author , Daniel A. BarocasDaniel A. Barocas More articles by this author , Li-Ching HuangLi-Ching Huang More articles by this author , Zhiguo ZhaoZhiguo Zhao More articles by this author , Karen E. HoffmanKaren E. Hoffman More articles by this author , Tatsuki KoyamaTatsuki Koyama More articles by this author , David F. PensonDavid F. Penson More articles by this author , and Christopher J.D. WallisChristopher J.D. Wallis More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003307.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Tobacco smoking negatively impacts cancer treatment and prognoses. However, there is limited evidence of its effect on cancer survivors' quality of life (QOL) and function. As the natural history of localized prostate cancer (PCa) is protracted, there is a need to identify modifiable risk factors that can influence survivorship, such as tobacco smoking. METHODS: We used 5-year data from the CEASAR (Comparative Effectiveness Analysis of Surgery and Radiation) study, a prospective, population-based, observational study of men diagnosed with localized PCa in 2011-2012. We excluded patients that did not complete the smoking-related and baseline questions and those that did not have at least one post-baseline response. Survivors were categorized as never, former, and current smokers. Multivariable linear regression models adjusting for baseline quality of life and function, treatment type, patient characteristics, and disease characteristics were used to assess the association between smoking history and 5-year scores on the 26-Item Expanded Prostate Index Composite (EPIC-26; PCa-specific domains: sexual, urinary incontinence, urinary irritative, bowel, and hormonal) and the Medical Outcomes Study 36-Item Short Form Survey (SF-36; general-health domains: physical, emotional, and energy and fatigue). RESULTS: We included 2185 men of which 109 (5%) were current smokers, 925 (42%) former smokers, and 1151 (53%) never smokers. In unadjusted analyses, current smokers had worse scores on all domains of EPIC-26 and SF-36 compared to never smokers (p<0.05). In adjusted analyses, there was no association between smoking history with EPIC-26 domains (all p>0.05). With regards to SF-36 outcomes, in adjusted analyses, compared to never smokers, current smokers had worse physical function (-7.53, 95%CI -11.16 to -3.89, p<0.01), emotional well-being (-5.03, 95%CI -7.78 to -2.27, p<0.01), and energy and fatigue (-4.51, 95%CI -7.73 to -1.28, p<0.01). Compared to never smokers, former smokers were only found to have worse physical function (-2.46, 95%CI -4.10 to -0.82, p<0.01). There was no interaction between smoking history and treatment (p>0.05). These findings were robust to more lenient definitions of smoking. CONCLUSIONS: PCa survivors that continue to smoke experience worse PCa-specific functional outcomes and physical functioning compared to never smokers. After adjustments, active smoking was associated with clinically relevant worse physical functioning. Tobacco smoking cessation in PCa survivors can enhance QOL and function regardless of initial treatment and should be integrated into survivorship care. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e755 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information David-Dan Nguyen More articles by this author Daniel A. Barocas More articles by this author Li-Ching Huang More articles by this author Zhiguo Zhao More articles by this author Karen E. Hoffman More articles by this author Tatsuki Koyama More articles by this author David F. Penson More articles by this author Christopher J.D. Wallis More articles by this author Expand All Advertisement PDF downloadLoading ...

Targeting HMGB1/PI3K/Akt and NF-κB/Nrf-2 signaling pathways by vildagliptin mitigates testosterone-induced benign prostate hyperplasia in rats

Benign prostatic hyperplasia (BPH) is a prevalent illness in older adults. It is well-recognized that testosterone is essential in the onset of BPH. Vildagliptin (Vilda), a dipeptidyl peptidase-IV inhibitor, has been shown to have anti-inflammatory and antioxidant effects. In this study, we studied the effects of vildagliptin on testosterone-induced BPH in rats and its underlying mechanisms. Forty male Wistar rats were allocated into four groups (n = 10): CTRL, Vilda, BPH, and BPH + Vilda groups. Our results revealed that vildagliptin treatment considerably lessened the prostate weight, prostate index, serum levels of prostate-specific antigen, 5α-reductase activity, and DHT levels compared to the testosterone group. Furthermore, vildagliptin treatment inhibited the expression of HMGB1, PI3K/Akt/NF-κB, and TNF-α signaling pathways in the prostate tissue of diseased rats. Additionally, vildagliptin treatment increased the expression of Nrf-2 and HO-1, reduced GSH levels, and lowered MDA levels. Besides, vildagliptin noticeably scaled up the level of cleaved caspase-3 enzyme and, conversely, the protein expression of proliferating cell nuclear antigen (PCNA). Correspondingly, vildagliptin counteracts testosterone-induced histological irregularities in rats' prostates. These findings suggest that vildagliptin may be a potential prophylactic approach to avoid BPH.

Quassinoids from Eurycoma longifolia Jack roots and their potential inhibitory activity against human benign prostatic hyperplasia cells (BPH-1) and testosterone-induced BPH rat model

Benign prostate hyperplasia (BPH) is an enlargement of the prostate gland, because of hormonal changes in aging males which contribute significantly to excessive proliferation over apoptosis of prostatic cells. The anti-proliferative and induced apoptotic activities of Eurycoma longifolia quassinoids on cancer cell lines could be promising therapeutic targets on BPH. Hitherto, no report of the quassinoids against BPH problem was available. In this study, a systematic phytochemical fractionation of the root extract, TAF2 was performed, which led to the discovery of nine previously described C20 quassinoids (1–9). Two undescribed C20 (10 and 12) and one undescribed (11) C19 quassinoids were identified by detailed NMR and HR-ESI-MS data analysis. Their absolute configurations were assigned by ECD spectral analysis. The quassinoids (1−12) were tested for inhibitory activity against the proliferation of human BPH-1 and human skin Hs27 fibroblast cells cultured in vitro. 1, 2 and 3 at 10 μM significantly reduced BPH-1 cell viability and were cytotoxic to Hs27 fibroblast cells. 2 was selected for further study of anti-BPH activity against testosterone induced BPH rats. At 5 mg/kg, 2 reduced the rat prostatic weight and prostatic index, consistent with the decrease in papillary acini number and epithelial thickness of the prostate tissues. These quassinoids may be potential anti-BPH compounds that require further studies.

Kolaviron modulates angiogenesis, apoptosis and inflammatory signaling in rat model of testosterone propionate-induced benign prostate hyperplasia.

Benign prostatic hyperplasia (BPH) is a non-malignant disease of the prostate characterized by uncontrolled proliferation of the prostate gland. Inflammation and oxidative stress have been reported to play a role in the development of BPH. Kolaviron, a bioflavonoid complex of Garcinia kola seed, has been shown to possess anti-inflammatory effect. In this study, we investigated the effect of Kolaviron on testosterone propionate (TP)-induced BPH in rats. Fifty male rats were assigned in 5 groups. Groups 1 and 2 were orally exposed to corn oil (2ml/kg) and Kolaviron (200mg/kg/day, p.o) for 28days. Group 3 rats received TP (3mg/kg/day, s.c) for 14days while Groups 4 and 6 were treated with Kolaviron (200mg/kg/day, p.o) and Finasteride (5mg/kg/day, p.o), respectively, for 14days prior to TP (3mg/kg, s.c) co-exposure for the remaining 14days. Administration of Kolaviron to TP-treated rats reverted histological alteration and significantly decreased prostate weight, prostate index, 5α-reductase, dihydrotestosterone, androgen receptor expression, tumor necrosis factor α, interleukin-1β, cyclooxygenase-2, prostaglandin E2, 5-lipoxygenase leukotriene B4, inducible nitric oxide synthase and nitric oxide concentration. In addition, Kolaviron alleviated TP-induced oxidative stress and reduced the expression of Ki-67, VEGF, and FGF to almost control levels. Furthermore, Kolaviron promoted apoptosis in TP-treated rats through downregulation of BCL-2 and upregulation of P53 and Caspase 3 expressions. Overall, Kolaviron prevented BPH via regulation of androgen/androgen receptor signaling, anti-oxidative and anti-inflammatory mechanisms.

Index lesion contouring on prostate MRI for targeted MRI/US fusion biopsy – Evaluation of mismatch between radiologists and urologists

PurposeMistargeting of focal lesions due to inaccurate segmentations can lead to false-negative findings on MRI-guided targeted biopsies. The purpose of this retrospective study was to examine inter-reader agreement of prostate index lesion segmentations from actual biopsy data between urologists and radiologists. MethodConsecutive patients undergoing transperineal MRI-targeted prostate biopsy for PI-RADS 3–5 lesions between January 2020 and December 2021 were included. Agreement between segmentations on T2w-images between urologists and radiologists was assessed with Dice similarity coefficient (DSC) and 95 % Hausdorff distance (95 % HD). Differences in similarity scores were compared using Wilcoxon test. Differences depending on lesion features (size, zonal location, PI-RADS scores, lesion distinctness) were tested with Mann-Whitney U test. Correlation with prostate signal-intensity homogeneity score (PSHS) and lesion size was tested with Spearman’s rank correlation. ResultsNinety-three patients (mean age 64.9 ± 7.1y, median serum PSA 6.5 [4.33–10.00]) were included. Mean similarity scores were statistically significantly lower between urologists and radiologists compared to radiologists only (DSC 0.41 ± 0.24 vs. 0.59 ± 0.23, p < 0.01; 95 %HD 6.38 ± 5.45 mm vs. 4.47 ± 4.12 mm, p < 0.01). There was a moderate and strong positive correlation between DSC scores and lesion size for segmentations from urologists and radiologists (ρ = 0.331, p = 0.002) and radiologists only (ρ = 0.501, p < 0.001). Similarity scores were worse in lesions ≤ 10 mm while other lesion features did not significantly influence similarity scores. ConclusionThere is significant mismatch of prostate index lesion segmentations between urologists and radiologists. Segmentation agreement positively correlates with lesion size. PI-RADS scores, zonal location, lesion distinctness, and PSHS show no significant impact on segmentation agreement. These findings could underpin benefits of perilesional biopsies.

A Contemporary Report of Low-Dose-Rate Brachytherapy for Prostate Cancer Using MRI for Risk Stratification: Disease Outcomes and Patient-Reported Quality of Life.

We examined a prospective consecutive cohort of low dose rate (LDR) brachytherapy for prostate cancer to evaluate the efficacy of monotherapy for unfavorable-intermediate risk (UIR) disease, and explore factors associated with toxicity and quality of life (QOL). 149 men with prostate cancer, including 114 staged with MRI, received Iodine-125 brachytherapy alone (144-145 Gy) or following external beam radiation therapy (110 Gy; EBRT). Patient-reported QOL was assessed by the Expanded Prostate Index Composite (EPIC) survey, and genitourinary (GU) and gastrointestinal (GI) toxicity were prospectively recorded (CTC v4.0). Global QOL scores were assessed for decline greater than the minimum clinically important difference (MCID). Univariate analysis (UVA) was performed, with 30-day post-implant dosimetry covariates stratified into quartiles. Median follow-up was 63 mo. Men with NCCN low (n = 42) or favorable-intermediate risk (n = 37) disease were treated with brachytherapy alone, while most with high-risk disease had combined EBRT (n = 17 of 18). Men with UIR disease (n = 52) were selected for monotherapy (n = 42) based on clinical factors and MRI findings. Freedom from biochemical failure-7 yr was 98%. Of 37 men with MRI treated with monotherapy for UIR disease, all 36 men without extraprostatic extension were controlled. Late Grade 2+/3+ toxicity occurred in 55/3% for GU and 8/2% for GI, respectively. Fifty men were sexually active at baseline and had 2 yr sexual data; 37 (74%) remained active at 2 yr. Global scores for urinary incontinence (UC), urinary irritation/obstruction (UIO), bowel function, and sexual function (SF) showed decreases greater than the MCID (p < 0.05) in UC at 2 mo, UIO at 2 and 6 mo, and SF at 2-24 mo, and >5 yr. Analysis did not reveal any significant associations with any examined rectal or urethral dosimetry for late toxicity or QOL. Disease outcomes and patient-reported QOL support LDR brachytherapy, including monotherapy for UIR disease.

PACE-A: An international phase 3 randomised controlled trial (RCT) comparing stereotactic body radiotherapy (SBRT) to surgery for localised prostate cancer (LPCa)—Primary endpoint analysis.

298 Background: People presenting with early-stage LPCa have several treatment options. There is therapeutic equipoise with lack of randomised evidence for superiority of radiotherapy or surgery. PACE-A aimed to determine if there is improved quality of life (QoL) following SBRT compared to surgery. Methods: PACE (NCT01584258) is a phase 3 open-label multiple-cohort RCT. In PACE-A, people with LPCa, T1-T2, Gleason≤3+4, PSA≤20ng/mL &amp; suitable for surgery were randomised (1:1) to SBRT or surgery. SBRT dose was 36.25Gy/5 fractions in 1-2 weeks; surgery was laparoscopic or robotically assisted prostatectomy. Androgen deprivation was not permitted. Co-primary endpoints were patient reported outcomes (PROs) of Expanded Prostate Index Composite (EPIC-26) questionnaire number of absorbent pads per day &amp; EPIC bowel subdomain score at 2 years. Target sample size was 234 participants (pts) to detect 9% difference in urinary incontinence (80% power, 5% 2-sided alpha) &amp; 5-point difference in mean bowel subdomain score (90% power, 5% 2-sided alpha) with higher EPIC score (range 0-100) indicating better QoL. Secondary endpoints included clinician reported toxicity and additional PROs (1% significance level). Analysis is by treatment received. Results: From Aug 2012 to Feb 2022, 123 men from 10 UK centres were randomised. The IDMC advised stopping recruitment after a 2-year gap in during COVID. Pts had median age 66years (IQR: 61, 69), median PSA 8ng/ml (6, 11) with 52% tumours ≥T2b and 79% Gleason 3+4; 93% pts were of white race. 58/63 pts received SBRT as allocated (2 received surgery, 2 unknown, 1 withdrawn); 48/60 received surgery as allocated (1 received SBRT, 3 received CRT, 2 unknown, 6 withdrawn). 8 laparoscopic and 42 robotic assisted operations were performed. Median follow-up is 50 months (IQR 41, 74). At 2 years, fewer SBRT pts reported use of urinary pads: 2/43 (4.5%) vs 15/32 (46.9%), p&lt;0.001. SBRT pts had significantly worse bowel subdomain score (mean (SD) 88.4 (12.7) vs 97.3 (5.5), p&lt;0.001). 7/45 (15.6%) SBRT and 0/31 (0%) surgery pts reported moderate/big problem with bowel symptoms (p=0.04). SBRT pts reported less EPIC sexual subdomain score (58.0 (31.9) vs 29.3 (20.5), p&lt;0.001); there was no evidence of a difference in urinary subdomain score (85.5 (19.8) vs 80.5 (20.8), p=0.29). At 2 years, CTCAE genitourinary grade 2 or higher(G2+) toxicity was seen in 5/54 (9.3%) SBRT vs 4/42 (9.5%) surgery pts (p=0.97); there was no G2+ gastrointestinal (GI) events seen in either group. Conclusions: PACE-A contributes the first randomised data to the comparison of SBRT with surgery in LPCa providing PRO data relevant to informed decision making. Compared to surgery, pts receiving SBRT had better urinary continence &amp; sexual bother score; clinician reported GI toxicity was low but SBRT pts reported more bowel bother at 2 years. Clinical trial information: NCT01584258 .

Comparison of four-year toxicities and local control of ultra-hypofractionated vs moderate-hypofractionated image guided prostate radiation with HDR brachytherapy boost: A phase I-II single institution trial

Purpose/Objective(s)To analyze the long term efficacy and safety of an ultra-hypofractionated (UHF) radiation therapy prostate treatment regimen with HDR brachytherapy boost (BB) and compare it to moderate-hypofractionated regimens (MHF). Materials/MethodsIn this single arm, prospective monocentric study, 28 patients with intermediate risk prostate cancer were recruited in an experimental treatment arm of 25 Gy in 5 fractions plus a 15 Gy HDR BB. They were then compared to two historical control groups, treated with either 36 Gy in 12 fractions or 37.5 Gy in 15 fractions with a similar HDR BB. The control groups included 151 and 311 patients respectively. Patient outcomes were reported using the International Prostate Symptom Score (IPSS) and Expanded Prostate Index Composite (EPIC-26) questionnaires at baseline and at each follow-up visit. ResultsMedian follow-up for the experimental arm was 48.5 months compared to 47 months and 60 months compared to the 36/12 and 37,5/15 groups respectively.The IPSS and EPIC scores did not demonstrate any significant differences in the gastrointestinal or genitourinary domains between the three groups over time. No biochemical recurrence occurred in the UHF arm as defined by the Phoenix criterion. ConclusionThe UHF treatment scheme with HDR BB seems equivalent to standard treatment arms in terms of toxicities and local control. Randomized control trials with larger cohorts are ongoing and needed to further confirm our findings.

Cinnamomum cassia and Rosa laevigata Mixture Improves Benign Prostatic Hyperplasia in Rats by Regulating Androgen Receptor Signaling and Apoptosis.

Benign prostatic hyperplasia (BPH) is the most common condition in elderly men that is characterized by an increase in the size of the prostate gland. Cinnamomum cassia and Rosa laevigata have been reported to treat the symptoms associated with BPH. The aim of this study was to evaluate the effects of HT080, an herbal extract of C. cassia and R. laevigata, on a testosterone propionate (TP)-induced BPH rat model. The rats received a daily subcutaneous injection of TP (3 mg/kg) for 4 weeks to induce BPH. Rats were divided into four groups: group 1 (sham), group 2 (BPH, TP alone), group 3 (Fina, TP + finasteride 1 mg/kg/day), and group 4 (HT080, TP + HT080 200 mg/kg/day). At the end of the experiment, all rats were sacrificed, and their prostate glands were removed, weighed, and subjected to histopathological examination and western blot analyses. Serum testosterone and dihydrotestosterone (DHT) levels were determined. In addition, serum alanine and aspartate aminotransferase levels were measured to evaluate the toxicity in the liver. The Hershberger bioassay was also conducted to investigate the effects of HT080 on androgenic and antiandrogenic activities. In the BPH model, the prostate weight, prostate index, prostate epithelial thickness, and serum testosterone and DHT levels in the HT080 group were significantly reduced compared to the BPH group. Histological studies showed that HT080 reduced prostatic hyperplasia. The protein expression of androgen receptor from the HT080 group was significantly reduced in comparison with the BPH group (p < 0.05). HT080 also induced apoptosis by regulating Bcl-2 and Bax expression. In addition, HT080 showed no toxicity in the liver and did not exhibit androgenic and antiandrogenic activities. Our finding revealed that HT080 can be a potential candidate for the treatment of BPH by regulating androgen receptor signaling and apoptosis.

Pharmacological Effects of the Lipidosterolic Extract from Kigelia africana Fruits in Experimental Benign Prostatic Hyperplasia Induced by Testosterone in Sprague Dawley Rats.

The use of phytotherapics is very frequent in men with prostatic diseases, sexual disorders and infertility, and many associations are commercially available. Various vegetable products used as drugs or nutraceuticals are attributed to possess the capacity to exert benefic effects on the reproductive system, and most of these drugs have a rich and varied lipidosterolic fraction, primarily responsible for the effects related to the male genital sphere. Kigelia africana (Lam.) Benth. (Bignoniaceae) is a plant used in African folk medicine as a vegetal remedy for various diseases, including some disorders of the male reproductive system; however, its potential activities have not yet been fully explored. The aim of the present study was to investigate whether the lipidosterolic hexane extract (LHE) from K. africana fruits, analyzed by comprehensive two-dimensional gas chromatography-mass spectrometry/flame ionization detection (GC×GC-MS/FID), can prevent or reverse benign prostatic hyperplasia (BPH) in rats. BPH was induced in experimental groups by daily subcutaneous injections of testosterone propionate (TP) for four weeks. β-sitosterol (β-s) was used as positive control. On day 28, the animals were sacrificed by cervical dislocation after anesthesia. Prostates were excised, weighed, and used for macroscopic and histological studies. Testosterone and dihydrotestosterone (DHT) levels in prostate were measured. The results showed that LHE significantly reduced the prostatic weight, prostatic index, prostatic levels of testosterone and DHT, and the histopathological alterations (including the epithelial thickness, stromal proliferation, and lumen area) induced by testosterone. These effects were superior to those demonstrated by β-s and appear to be due to a partial antiandrogenic activity of LHE. The results obtained showed that the LHE can prevent, and reverse testosterone induced prostatic hyperplasia, and support the traditional use of Kigelia africana in some disorders of the reproductive system.

Effects of Isoflavone-Rich NADES Extract of Pueraria lobata Roots and Astaxanthin-Rich Phaffia rhodozyma Extract on Prostate Carcinogenesis in Rats.

Prostate cancer (PCa) is one of the most common male malignancies worldwide. In the current study, we evaluated the effects of a natural deep eutectic solvent (NADES) extract of Pueraria lobata roots rich in isoflavones (ISF) and Phaffia rhodozyma extract rich in astaxanthin (ASX) on an N-methyl-N-nitrosourea plus testosterone PCa model in rats. ISF consisted of puerarin, daidzein, genistein, formononetin and other polyphenols, while ASX contained lipids and unsaturated species in addition to astaxanthin. Extracts were administered through a whole promotion period in daily doses shown by our group to successfully inhibit benign prostate hyperplasia (BPH) development - 200 mg/kg for ISF and 25 mg/kg for ASX. Though a similar effect was found for BPH processes accompanying PCa induction, the incidence of PCa in animals treated with placebo, ISF and ASX was 37%, 37% and 41%, respectively, showing no chemopreventive activity of ISF and ASX. PCa development was associated with a decrease in the Ca/Mg ratio in serum and an increase in prostate tissue. Treatment with both extracts produced a normalization effect on Ca balance in serum, which, combined with a decrease in the prostatic index, suggests some positive health effects of ISF and ASX.

Retzius-sparing robot-assisted radical prostatectomy in a medium size oncological center holds adequate oncological and functional outcomes

Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) has emerged as a surgical option for patients with prostatic cancer in high-volume centers. The objective is to assess oncological and functional outcomes when implementing RS-RARP in a medium-volume center without previous experience of robotic surgery. This is a prospective observational single-center study. Patients operated between July 2017 and April 2020 were divided into two consecutive groups, A and B, each with 104 patients. The surgeons had prior experience in laparoscopic surgery and underwent robotic training. Positive surgical margin (PSM) status, urinary continence, and erectile function projected by Kaplan–Meier curves, together with patient reported quality of life outcomes at 12 months post-surgery were documented. Median patient age was 63 years (IQR = 59–67), overall PSM rate were 33%, 28% for pT2 disease. Pre-operative values showed no significant difference between both groups. The rate of urinary continence dropped from 81 to 78% (SE = 5.7) (Group A) and from 90 to 72% (SE = 6.3) (Group B) using the International Consultation on Incontinence Questionnaire-Short Form. Baseline sexual function was regained in 41% (Group A) and 47% (Group B) of patients. The median Expanded Prostate Index Composite-26 total score decreased from 86 to 82. These outcomes relate favorably to prior reports. There was a clinically significant decrease in median operative time in the successive groups with post-operative complications occurring in less than 2% of surgical procedures overall. A 12-month follow-up suggests that RS-RARP may be safely introduced in a medium-volume center without previous experience of robotic surgery.

Effect of bark extract of Prunus domestica in experimental prostatic hyperplasia in Wistar rats

Background: Benign prostatic hyperplasia (BPH) is a non-malignant enlargement of prostate resulting in urinary obstruction, along with irritant urinary tract symptoms. The present pharmacological management of above condition although successful has some limitations due to adverse effects of drugs. Aims and Objectives: Phytotherapeutic agents are used in different countries for treatment of BPH. In this study, attempts have been made to find out the effect of bark extract of Prunus domestica in testosterone induced benign hyperplasia of prostate in Wistar albino rats. Materials and Methods: Animals were divided into different groups, each containing six animals. Group I (control) received Arachis oil S/C for 21 days followed by distilled water orally for another 21 days. Group II animals were treated with testosterone (2 mg/kg) S/C for 21 days followed by distilled water orally for another 21 days (positive control). Group III (standard treatment group) was given testosterone (2 mg/kg) S/C for 21 days followed by Finasteride (1 mg/kg) orally for another 21 days. Group IV and Group V animals were treated with testosterone (2 mg/kg) S/C for 21 days followed by aqueous extract of bark of P. domestica (200 and 400 mg/kg) orally for another 21 days. After the 21st day of treatment, blood collection was done from retro orbital plexus by applying light ether anesthesia. Finally the animals were sacrificed and prostate glands were dissected and weighed. The parameters such as physical (body weight, prostate weight, and prostatic index [PI]), biochemical (Serum testosterone and Serum prostatic acid phosphatase), and histopathological study were done. Results were evaluated by One-way ANOVA followed by post hoc Tukey’s multiple comparison test. Results: Administration of P. domestica bark extract reduced the size of prostate and the PI significantly (P &lt; 0.001) when compared to positive control. The histopathological examination showed mild glandular proliferation with normal epithelial and stromal component as compared to positive control group. Conclusion: P. domestica extract can be an alternative to conventional drugs for management of BHP. Further detail study with active principles is required to assess the detail mechanism of action.

Inhibitory effects of Calocybe indica macrofungi on experimental benign prostatic hyperplasia in rats.

This study was designed to investigate the protective effects of Calocybe indica extract on testosterone-induced benign prostatic hyperplasia in rats. In this study, 60 adult Sprague Dawley rats were randomly divided into six equal groups, one group served as the normal control, five of the groups were administered subcutaneous testosterone propionate for 28 days to induce benign prostatic hyperplasia, three of the five groups were simultaneously administered three graded doses of C. indica extract while one group was administered finasteride as the standard drug and the other left as untreated BPH model group given testosterone propionate only. BPH in the prostate gland was detected through gross appearance, prostate weight, and biochemical and histopathological analyses. Increased prostate weight, serum prostate-specific antigen (PSA), and epithelial thickness were observed in the untreated testosterone-induced BPH model. Administration of finasteride and C. indica extract led to a reduction in prostate weight, prostatic index, serum PSA, serum levels of testosterone, and prostatic epithelial thickness, and increased luminal diameter. Administration of C. indica extract suppressed the pathophysiological effects of benign prostatic hyperplasia in rats. Thus, C. indica mushroom is a potential pharmacological candidate for the management of BPH in man or dogs.