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2.
J Urol ; 211(5): 648-655, 2024 May.
Article in English | MEDLINE | ID: mdl-38591703

ABSTRACT

PURPOSE: Benefits of docetaxel-based neoadjuvant chemohormonal therapy (NCHT) before radical prostatectomy (RP) remain largely unknown. We explored whether docetaxel-based NCHT would bring pathological benefits and improve biochemical progression-free survival (bPFS) over neoadjuvant hormonal therapy (NHT) in locally advanced prostate cancer. MATERIALS AND METHODS: A randomized trial was designed recruiting 141 locally advanced, high-risk prostate cancer patients who were randomly assigned at the ratio of 2:1 to the NCHT group (75 mg/m2 body surface area every 3 weeks plus androgen deprivation therapy for 6 cycles) and the NHT group (androgen deprivation therapy for 24 weeks). The primary end point was 3-year bPFS. Secondary end points were pathological response including pathological downstaging and minimal residual disease rates. RESULTS: The NCHT group showed significant benefits in 3-year bPFS compared to the NHT group (29% vs 9.5%, P = .002). At a median follow-up of 53 months, the NCHT group achieved a significantly longer median bPFS time than the NHT group (17 months vs 14 months). No significant differences were found between the 2 groups in pathological downstaging and minimal residual disease rates. CONCLUSIONS: NCHT plus RP achieved significant bPFS benefits when compared with NHT plus RP in high-risk, locally advanced prostate cancer. A larger cohort with longer follow-up duration is essential in further investigation.


Subject(s)
Prostatic Neoplasms , Male , Humans , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/surgery , Docetaxel , Neoadjuvant Therapy , Androgen Antagonists/therapeutic use , Prospective Studies , Androgens , Neoplasm, Residual/surgery , Prostatectomy , Prostate-Specific Antigen
3.
Front Immunol ; 14: 1133160, 2023.
Article in English | MEDLINE | ID: mdl-37033924

ABSTRACT

Introduction: Cancer-associated fibroblasts (CAFs) are one of the most abundant cell types in tumor microenvironment. However, the phenotypic and functional heterogeneities among CAFs have not been sufficiently investigated in prostate cancer. Methods: We obtained and analyzed the single-cell RNA-sequencing data from 26 hormone-sensitive prostate cancer samples and 8 castration-resistant prostate cancer samples, along with the analysis of bulk-sequencing datasets. Furthermore, we performed multicolor immunofluorescence staining to verify the findings from the data analysis. Results: We identified two major CAFs subtypes with distinct molecular characteristics and biological functions in prostate cancer microenvironment, namely αSMA+ CAV1+ CAFs-C0 and FN1+ FAP+ CAFs-C1. Another single-cell RNA-sequencing dataset containing 7 bone metastatic prostate cancer samples demonstrated that osteoblasts in the bone metastatic lesions comprised two subtypes with molecular characteristics and biological functions similar to CAFs-C0 and CAFs-C1 in the primary tumor sites. In addition, we discovered a transcriptional factor regulatory network depending on CAFs-C1. CAFs-C1, but not CAFs-C0, was associated with castration resistance and poor prognosis. We also found that CAFs-C1 signature was involved in treatment resistance to immune checkpoint inhibitors. Discussion: In summary, our results identified the presence of heterogeneous CAFs subtypes in prostate cancer microenvironment and the potential of specific CAFs subtype as therapeutic target for castration-resistant prostate cancer.


Subject(s)
Cancer-Associated Fibroblasts , Prostatic Neoplasms, Castration-Resistant , Male , Humans , Cancer-Associated Fibroblasts/metabolism , Prostatic Neoplasms, Castration-Resistant/genetics , Prostatic Neoplasms, Castration-Resistant/metabolism , Prostatic Neoplasms, Castration-Resistant/pathology , RNA/metabolism , Tumor Microenvironment
4.
Spectrochim Acta A Mol Biomol Spectrosc ; 293: 122426, 2023 May 15.
Article in English | MEDLINE | ID: mdl-36787677

ABSTRACT

We collected surface-enhanced Raman spectroscopy (SERS) data from the serum of 729 patients with prostate cancer or benign prostatic hyperplasia (BPH), corresponding to their pathological results, and built an artificial intelligence-assisted diagnosis model based on a convolutional neural network (CNN). We then evaluated its value in diagnosing prostate cancer and predicting the Gleason score (GS) using a simple cross-validation method. Our CNN model based on the spectral data for prostate cancer diagnosis revealed an accuracy of 85.14 ± 0.39%. After adjusting the model with patient age and prostate specific antigen (PSA), the accuracy of the multimodal CNN was up to 88.55 ± 0.66%. Our multimodal CNN for distinguishing low-GS/high-GS and GS = 3 + 3/GS = 3 + 4 revealed accuracies of 68 ± 0.58% and 77 ± 0.52%, respectively.


Subject(s)
Artificial Intelligence , Prostatic Neoplasms , Male , Humans , Early Detection of Cancer , Prostatic Neoplasms/diagnosis , Prostate-Specific Antigen , Neural Networks, Computer
5.
BMC Pregnancy Childbirth ; 22(1): 802, 2022 Nov 01.
Article in English | MEDLINE | ID: mdl-36319955

ABSTRACT

BACKGROUND: With the extensive use of aspirin in obstetrics and reproductive medicine, concerns of potentially related congenital anomalies have been raised in previous studies. However, there is a lack of evidence concerning the safety of application of aspirin during pregnancy in Chinese population, especially during the first trimester. PATIENTS AND METHODS: We retrospectively included a total of 2,763 patients with 2,856 fetuses (2670 singleton births and 93 pairs of twins), among whom 1,684 took low dose aspirin (LDA) during pregnancy (the LDA group) and the other 1,079 were not exposed to LDA (the control group). The primary outcome was the rate of fetal congenital anomalies, and was compared between the LDA group and the control group. We also conducted logistic regression to examine the potential risk factors of congenital abnormalities. RESULTS: The average daily dose of LDA taken was 67.6 mg. The rate of congenital anomalies was comparable between the two groups, suggesting low teratogenicity of LDA application during pregnancy (3.3% vs. 2.8%; P = 0.421). The duration of LDA exposure and the time of LDA exposure showed no association with congenital anomalies. A previous history of fetal congenital anomalies was associated with an increased risk of the recurrence of congenital anomalies in the siblings (adjusted OR = 3.00, 95% CI: 1.00-8.60; P = 0.041). CONCLUSION: Exposure to LDA during pregnancy did not increase the risk of congenital anomalies in the fetus, suggesting that it was safe to apply LDA during pregnancy. A history of previous fetal abnormalities was found to be an independent risk factor of congenital anomalies. Our study suggests that LDA can be safely applied during pregnancy without increasing risks of congenital anomalies.


Subject(s)
Aspirin , Prenatal Care , Pregnancy , Female , Humans , Retrospective Studies , Fetus , Pregnancy Trimester, First
6.
Curr Oncol ; 29(9): 6373-6382, 2022 09 05.
Article in English | MEDLINE | ID: mdl-36135071

ABSTRACT

To explore the diagnostic value of the Prostate Imaging−Reporting and Data System version 2.1 (PI-RADS v2.1) for clinically significant prostate cancer (CSPCa) in patients with a history of transurethral resection of the prostate (TURP), we conducted a retrospective study of 102 patients who underwent systematic prostate biopsies with TURP history. ROC analyses and logistic regression analyses were performed to demonstrate the diagnostic value of PI-RADS v2.1 and other clinical characteristics, including PSA and free/total PSA (F/T PSA). Of 102 patients, 43 were diagnosed with CSPCa. In ROC analysis, PSA, F/T PSA, and PI-RADS v2.1 demonstrated significant diagnostic value in detecting CSPCa in our cohort (AUC 0.710 (95%CI 0.608−0.812), AUC 0.768 (95%CI 0.676−0.860), AUC 0.777 (95%CI 0.688−0.867), respectively). Further, PI-RADS v2.1 scores of the peripheral and transitional zones were analyzed separately. In ROC analysis, PI-RADS v2.1 remained valuable in identifying peripheral-zone CSPCa (AUC 0.780 (95%CI 0.665−0.854; p < 0.001)) while having limited capability in distinguishing transitional zone lesions (AUC 0.533 (95%CI 0.410−0.557; p = 0.594)). PSA and F/T PSA retain significant diagnostic value for CSPCa in patients with TURP history. PI-RADS v2.1 is reliable for detecting peripheral-zone CSPCa but has limited diagnostic value when assessing transitional zone lesions.


Subject(s)
Prostatic Neoplasms , Transurethral Resection of Prostate , Humans , Magnetic Resonance Imaging , Male , Prostate/diagnostic imaging , Prostate/pathology , Prostate/surgery , Prostate-Specific Antigen , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Retrospective Studies
7.
Spectrochim Acta A Mol Biomol Spectrosc ; 281: 121603, 2022 Nov 15.
Article in English | MEDLINE | ID: mdl-35868057

ABSTRACT

PURPOSE: To identify and compare the capacities of serum and serum-derived small extracellular vesicles (EV) in diagnosis of common urogenital cancer combining Surface-enhanced Raman spectroscopy (SERS) and Convolutional Neural Networks (CNN). MATERIALS AND METHODS: We collected serum samples from 32 patients with prostate cancer (PCa), 33 patients with renal cell cancer (RCC) and 30 patients with bladder cancer (BCa) as well as 35 healthy control (HC), which were thereafter used to enrich extracellular vesicles by ultracentrifuge. Label-free SERS was utilized to collect Raman spectra from serum and matched EV samples. We constructed CNN models to process SERS data for classification of malignant patients and healthy controls (HCs). RESULTS: We collected 650 and 1206 spectra from serum and serum-derived EV, respectively. CNN models of EV spectra revealed high testing accuracies of 79.3%, 78.7% and 74.2% in diagnosis of PCa, RCC and BCa, respectively. In comparison, serum SERS-based CNN model had testing accuracies of 73.0%, 71.1%, 69.2% in PCa, RCC and BCa, respectively. Moreover, CNN models based on EV SERS data show significantly higher diagnostic capacities than matched serum CNN models with the area under curve (AUC) of 0.80, 0.88 and 0.74 in diagnosis of PCa, RCC and BCa, respectively. CONCLUSION: Deep learning-based SERS analysis of EV has great potentials in diagnosis of urologic cancer outperforming serum SERS analysis, providing a novel tool in cancer screening.


Subject(s)
Carcinoma, Renal Cell , Deep Learning , Extracellular Vesicles , Kidney Neoplasms , Algorithms , Humans , Kidney Neoplasms/diagnosis , Male , Spectrum Analysis, Raman/methods
8.
Exp Cell Res ; 415(2): 113138, 2022 06 15.
Article in English | MEDLINE | ID: mdl-35398308

ABSTRACT

Serine hydroxymethyltransferase 2 (SHMT2) is a key enzyme that regulates serine/glycine transition; however, its specific function and molecular mechanisms in tumors remain controversial. In this study, we aimed to enhance the understanding in this regard. Through in vitro and in vivo experiments, as well as data analyses using public databases, we investigated the effect of SHMT2 in prostate cancer. Our results indicated that SHMT2 acts as a prostate cancer tumor proliferation suppressor and negatively regulates the aggressive behavior of prostate cancer through activation of epithelial-mesenchymal transition. Additionally, downregulated SHMT2 expression was observed in more advanced prostate cancer phenotypes, and further analysis showed that its depletion promoted proliferation and migration in prostate cancer cell lines. Taken together, our results revealed the function of SHMT2 in prostate cancer and may potentially play a role in the exploration of new therapeutic strategies.


Subject(s)
Epithelial-Mesenchymal Transition , Prostatic Neoplasms , Cell Line, Tumor , Cell Proliferation/genetics , Down-Regulation/genetics , Epithelial-Mesenchymal Transition/genetics , Glycine Hydroxymethyltransferase/genetics , Glycine Hydroxymethyltransferase/metabolism , Humans , Male , Neoplasm Metastasis , Prostatic Neoplasms/genetics
9.
Int J Nanomedicine ; 17: 1635-1646, 2022.
Article in English | MEDLINE | ID: mdl-35411143

ABSTRACT

Objective: To explore the value of surface-enhanced Raman spectroscopy analysis of pretreated plasma samples in prediction of bladder cancer (BCa) recurrence after neoadjuvant chemotherapy (NAC) and radical cystectomy (RC). Patients and Methods: SERS was used to analyze plasma samples collected before biopsy and treatment in BCa patients undergoing NAC and RC. The value of clinicopathological parameters and distinctive SERS peaks in the prediction of disease recurrence were analyzed in Cox regression proportional hazard analysis and Log rank test. Principal component analysis and linear discriminant analysis (PCA-LDA) were employed to process spectral data and construct diagnostic algorithms. Results: A total of 88 patients with 440 plasma SERS spectra were collected. The SRES spectra from recurrent patients were compared with patients who remained recurrence free. The SERS demonstrated higher levels of circulating free nucleic acid components in recurrent population, which is represented by significantly higher intensities at SERS peaks of 725 cm-1, 1328 cm-1 and 1455 cm-1. The SERS also detected significantly lower levels of tryptophan shown as lower significantly intensities at the 1558 cm-1, which is proved to be an independent predictor of BCa recurrence. The addition of SERS peaks of 1558 cm-1 to classic clinicopathological predictors including pathological tumor stage, lymph node metastasis and pathological downstaging can significantly enhance the power of the predictive model from 0.66 to 0.76 in the area under curve (AUC) of receiver operating characteristic (ROC) curves. Meanwhile, the PCA-LDA diagnostic model based on SERS spectra reveals a high accuracy of 85.2% in prediction of disease recurrence and the AUC of 0.92 in the ROC curve. When validated in the leave-one-out cross-validation method, the accuracy of the model remained 84.1%. Conclusion: We show that SERS analysis of plasma before NAC treatment can accurately classify patients with different risks of disease recurrence after surgery and improve the power of clinicopathological predictive models, thus refining clinical decision-making.


Subject(s)
Cystectomy , Urinary Bladder Neoplasms , Cystectomy/methods , Humans , Muscles/pathology , Neoadjuvant Therapy , Spectrum Analysis, Raman/methods , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/surgery
10.
Urology ; 167: 144-151, 2022 09.
Article in English | MEDLINE | ID: mdl-35331776

ABSTRACT

OBJECTIVE: To compare cognitive outcomes of patients undergoing open radical nephrectomy (RN) and inferior vena cava (IVC) thrombectomy with vs without cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest. PATIENTS AND METHODS: A prospective, 6-month, observational study was conducted from January 2013 to December 2019 in renal cell carcinoma patients with level II-IV IVC thrombus undergoing RN. A battery of standardized neuropsychological tests was administrated to assess multi-domain cognitive function before surgery, 1 week, and 6 months after surgery: attention, executive functions, working memory, short-term and long-term delay recall, visuomotor speed, and verbal fluency. RESULTS: Cognitive impairment was defined as a 20% reduction in at least 20% of the main variables. The primary outcome was the incidence of cognitive impairment at 6 months postoperatively and was analyzed with general linear mixed models. Twenty-six patients treated with CPB and 39 treated with non-CPB were analyzed. There were no significant differences in cognitive impairment between the two groups. The incidence of cognitive impairment at 1 week postoperatively was 38.5% in CPB group and 30.8% in non-CPB group (P = .52), after 6 months 11.5% and 10.3% (P = 1.00). Multivariate analysis indicated that the estimated blood loss was the only risk factor associated with cognitive impairment at 1 week postoperatively. CONCLUSION: This study showed no significant differences in postoperative cognitive function of renal cell carcinoma patients after open RN and IVC thrombectomy with and without CPB and deep hypothermic circulatory arrest. Estimated blood loss was found to be associated with cognitive impairment at 6 months postoperatively.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Thrombosis , Carcinoma, Renal Cell/complications , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/surgery , Cardiopulmonary Bypass/adverse effects , Circulatory Arrest, Deep Hypothermia Induced , Cognition , Humans , Kidney Neoplasms/complications , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Nephrectomy/adverse effects , Prospective Studies , Retrospective Studies , Thrombectomy , Thrombosis/surgery , Vena Cava, Inferior/surgery
11.
Front Oncol ; 12: 791140, 2022.
Article in English | MEDLINE | ID: mdl-35280720

ABSTRACT

Purpose: To determine the safety and feasibility of extraperitoneal laparoscopic extended lymph node dissection (LND) at the time of extraperitoneal laparoscopic radical nephroureterectomy (RNU). Materials and Methods: Between May 2018 and March 2019, 39 patients with upper tract urothelial carcinoma (UTUC) received extraperitoneal laparoscopic RNU and concomitant extraperitoneal laparoscopic extended LND. All patients were followed for at least 90 days. Perioperative and pathological data including nodal status and perioperative complications were collected. Results: Among all 39 patients, 12 patients had pT1, 6 had pT2, 20 had pT3 disease, and 1 had T4 disease. The median (range) lymph node count was 10 (5-22), with 8 patients having pathologically proven lymph node metastasis. The median (range) operating time was 225 (165-430) min, and the median estimated blood loss was 200 (60-800) ml. The median postoperative hemoglobin loss was 1.6 (0-4.2) g/dl. The median (range) postoperative hospital stays were 6 (3-26) days. Overall, 7 patients experienced minor (Clavien Grade I-II) postoperative complications with five patients having Clavien Grade I complications and two patients having Clavien Grade II complications. No major complication (Clavien grade III-IV) occurred. With a median follow-up of 38 months, a total of 8 patients (20.5%) developed local or distant recurrence and no regional LNs where extended LND were performed had recurrence. Conclusions: The present prospective study demonstrated that extraperitoneal laparoscopic extended LND during extraperitoneal laparoscopic RNU for UTUC is a feasible and safe procedure which provides minimal invasion, rapid recovery, and potentially lower risk of regional LN recurrence. Larger prospective clinical trials with survival endpoints are needed to further determine its potential therapeutic benefits. Trial Registration: ClinicalTrials.gov identifier NCT03544437 www.clinicaltrials.gov.

12.
Nanomedicine ; 29: 102245, 2020 10.
Article in English | MEDLINE | ID: mdl-32592757

ABSTRACT

Prostate cancer most frequently metastasizes to bone, resulting in abnormal bone metabolism and the release of components into the blood stream. Here, we evaluated the capacity of convolutional neural networks (CNNs) to use Raman data for screening of prostate cancer bone metastases. We used label-free surface-enhanced Raman spectroscopy (SERS) to collect 1281 serum Raman spectra from 427 patients with prostate cancer, and then we constructed a CNN based on LetNet-5 to recognize prostate cancer patients with bone metastases. We then used 5-fold cross-validation method to train and test the CNN model and evaluated its actual performance. Our CNN model for bone metastases detection revealed a mean training accuracy of 99.51% ± 0.23%, mean testing accuracy of 81.70% ± 2.83%, mean testing sensitivity of 80.63% ± 5.07%, and mean testing specificity of 82.82% ± 2.94%.


Subject(s)
Bone Neoplasms/blood , Early Detection of Cancer , Neoplasm Proteins/blood , Prostatic Neoplasms/blood , Bone Neoplasms/genetics , Bone Neoplasms/pathology , Bone Neoplasms/secondary , Humans , Male , Nanoparticles/chemistry , Neoplasm Proteins/isolation & purification , Neural Networks, Computer , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Spectrum Analysis, Raman
13.
Urol Oncol ; 38(6): 601.e1-601.e9, 2020 06.
Article in English | MEDLINE | ID: mdl-32241690

ABSTRACT

PURPOSE: To predict Gleason grade group (GG) upgrade in biopsy Gleason grade group 1 (GG1) prostate cancer (CaP) patients using surface-enhanced Raman spectroscopy (SERS). MATERIALS AND METHODS: Preoperative serum samples of patients with biopsy GG1 and subsequent radical prostatectomy were analyzed using SERS. The role of clinical variables and distinctive SERS spectra in the prediction of GG upgrade were evaluated. Principal component analysis and linear discriminant analysis (PCA-LDA) were used to manage spectral data and develop diagnostic algorithms. RESULTS: A total of 342 preoperative serum SERS spectra from 114 patients were obtained. SERS detected a higher level of circulating free nucleic acid bases and a lower level of lipids in patients with GG upgrade to GG3 and higher, presenting as SERS spectral peaks of 728 cm-1 and 1,655 cm-1, respectively. Both spectral peaks were independent predictors of GG upgrade and their addition to clinical predictors of PSA and positive core percent significantly improved predictive power of the logistic regression model with area under curve improved from 0.65 to 0.80 (P = 0.0045). Meanwhile, PCA-LDA diagnostic model based on serum SERS spectra showed a high accuracy of 91.2% in predicted groups and remained stable with a sensitivity, specificity, and accuracy of 65%, 97.3%, 86.0%, respectively when validated by leave-one-out cross-validation method. CONCLUSIONS: By analyzing preoperative serum samples, SERS combined with PCA-LDA model could be a promising tool for prediction of Gleason GG upgrade in biopsy GG1 CaP and assist in treatment decision-making in clinical practice.


Subject(s)
Prostate/pathology , Prostatic Neoplasms/blood , Prostatic Neoplasms/pathology , Spectrum Analysis, Raman/methods , Aged , Biopsy , Humans , Male , Middle Aged , Neoplasm Grading , Predictive Value of Tests , Preoperative Period
14.
J Cancer Res Clin Oncol ; 146(3): 687-694, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31745702

ABSTRACT

OBJECTIVE: To assess the use of the cell cycle progression (CCP) score versus actual risk stratification practice in making treatment decisions for prostate cancer patients with locally adverse pathology after radical prostatectomy (RP). PATIENTS AND METHODS: Men with adverse pathologic features, pT3 or positive surgical margins who underwent RP in 2010-2014 at Renji hospital were retrospectively analyzed. The primary outcome was biochemical recurrence (BCR) after RP. RNA was quantified from paraffin-embedded RP specimens. The CCP score was calculated as average expression of 31 CCP genes, normalized to 15 housekeeper genes. The prognostic utility of the CCP score was assessed using Kaplan-Meier analysis and multivariable Cox proportional hazards model. RESULTS: Among the 100 men identified, 5-year BCR-free survival for the low- (< 0), intermediate- (0-1) and high- (> 1) CCP score groups was 89.3%, 38.8%, and 12.9%, respectively. In multivariable models adjusting for clinical and pathological variables with the cancer of the prostate risk assessment post-surgical (CAPRA-S) score, both continuous CCP score [hazard ratio (HR) 1.373 per unit score, 95% confidence interval (CI) 1.006-1.874; p = 0.046) and the categorized CCP score (p < 0.001)were independent predictors of BCR. CONCLUSIONS: The present study provides insights into the role the CCP score plays in risk stratification of this cohort and in determining candidacy for deferred secondary treatment. From our perspective, the CCP score allows better stratification and can help identifying patients at lower risk of disease recurrence who could benefit from a wait-and-see policy.


Subject(s)
Cell Cycle/physiology , Prostatic Neoplasms/pathology , Aged , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Prognosis , Prostatectomy , Prostatic Neoplasms/surgery , Retrospective Studies , Risk Assessment/methods
15.
Urol Oncol ; 37(12): 991-998, 2019 12.
Article in English | MEDLINE | ID: mdl-31466813

ABSTRACT

OBJECTIVE: Docetaxel has been shown to be an effective chemotherapy agent when combined with androgen deprivation therapy for hormone sensitive metastatic prostate cancer (CaP). Since very high risk CaP has a high rate of occult metastatic disease and early recurrence, we hypothesize that patients with very high risk locally advanced CaP may benefit from docetaxel-based neoadjuvant chemohormonal therapy (NCHT). Thus, we conducted a retrospective study to identify the outcome of these patients treated with NCHT followed by radical prostatectomy (RP). PATIENTS AND METHODS: We retrospectively analyzed data from 177 consecutive patients who had very high risk locally advanced CaP between March 2014 and July 2017. Patients received 3 different therapies: (i) 60 men in NCHT group, (ii) 73 men in neoadjuvant hormonal therapy (NHT) group, and (iii) 44 men received immediate RP without neoadjuvant therapy (No-NT group). Surgical outcomes were analyzed and survival differences were compared by the Kaplan-Meier method. RESULTS: The NCHT group had statistically significant higher preoperative Prostate-Specific Antigen (PSA) (P < 0.002), higher Gleason score (P < 0.002), and more advanced clinical stage (P < 0.001) than other groups. After RP, 81% (42/52) of patients in NCHT group, 73% (51/70) of patients in NHT group, and 48% (21/44) of patients in No-NT group achieved an undetectable PSA (P < 0.001). A total of 14% (6/42) patients achieving a postoperative undetectable PSA experienced biochemical recurrence in the NCHT group, with median biochemical progression-free survival (bPFS) time of 19 months; 47% (24/51) experienced biochemical recurrence in the NHT group, with median bPFS time of 13 months; 81% (17/21) experienced biochemical recurrence in the No-NT group, with median bPFS time of 9 months (P < 0.001). The median follow-up time of 3 groups was 12.5 months in the NCHT group, 18.3 months in the NHT group, and 22.8 months in the No-NT group (P = 0.01). CONCLUSION: Despite having poorer prognostic factors, the NCHT group had better bPFS time after surgery compared to NHT and No-NT groups. Randomized controlled investigations are needed to validate these results and further follow-up is required for survival endpoints.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymph Node Excision/methods , Neoadjuvant Therapy/methods , Prostatectomy , Prostatic Neoplasms/therapy , Aged , Androgen Antagonists/therapeutic use , Antineoplastic Agents, Hormonal/therapeutic use , Disease Progression , Docetaxel/therapeutic use , Follow-Up Studies , Humans , Kallikreins/blood , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Pelvis/surgery , Progression-Free Survival , Prostate/pathology , Prostate/surgery , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/mortality , Prostatic Neoplasms/pathology , Retrospective Studies
16.
Prostate ; 78(4): 250-256, 2018 03.
Article in English | MEDLINE | ID: mdl-29285775

ABSTRACT

OBJECTIVE: To compare the antitumor effect of abiraterone (AA) followed by docetaxel-prednisone (DP) or vice versa in metastatic castration-resistant prostate cancer (mCRPC) patients, and explored factors that might predict combined PSA-PFS, combined rPFS and OS. PATIENTS AND METHODS: We retrospectively analyzed mCRPC patients treated with sequential therapy using DP followed by AA or vice versa. Patients who had received enzalutamide or cabazitaxel were excluded. The primary outcome measure was overall survival (OS). The combined PSA progression-free survival (PSA-PFS), combined radiographic PFS (rPFS), and OS of AA-to-DP were compared to the reverse sequence using Kaplan-Meier curves with log-rank statistics. Univariable and multivariable Cox regression analyses were performed to determine prognostic factors that were associated with combined PSA-PFS, combined rPFS and OS. RESULTS: A total of 104 mCRPC patients who began treatment between 2013 and 2017 were identified: 42 were in the DP-to-AA group and 62 were in the AA-to-DP group. There was no significant difference of baseline clinical characteristics between AA-to-DP and DP-to-AA group. In addition, there was no significant difference in combined PSA-PFS (AA-to-DP: 12.5 [11.4-13.6] vs DP-to-AA: 13.2 [10.9-15.5] months [P = 0.127]), combined rPFS (AA-to-DP: 12.2 [10.9-13.4] vs DP-to-AA: 11.2 [8.9-13.5] months [P = 0.183]) and OS (AA-to-DP: 23.3 [19.7-26.9] vs DP-to-AA: 22.9 [22.1-23.7] months [P = 0.213]) between the two treatment sequences in Kaplan-Meier analysis. In multivariate Cox regression analysis, high systematic Immune-Inflammation Index (SII) level, which was calculated by P (platelet) × N (neutrophil)/L(lymphocyte), remained significant predictors of OS, combined rPFS and combined PSA-PFS. CONCLUSION: In this study, we did not observe differences in clinical outcomes based on alternative sequencing of AA and DP in mCRPC patients. The ability to tolerate side effects and patient preference may be used to determine the treatment sequencing. In addition, high pretreatment SII level is a negative independent prognosticator of survival outcomes in mCRPC with sequential therapy using DP followed by AA or vice versa, which might guide clinicians select the best treatment.


Subject(s)
Androstenes/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Docetaxel/administration & dosage , Prostatic Neoplasms, Castration-Resistant/drug therapy , Aged , Biomarkers/blood , Humans , Male , Middle Aged , Prednisone/administration & dosage , Prognosis , Prostate-Specific Antigen/blood , Prostatic Neoplasms, Castration-Resistant/mortality , Prostatic Neoplasms, Castration-Resistant/pathology , Retrospective Studies , Severity of Illness Index , Survival Analysis , Systemic Inflammatory Response Syndrome/etiology , Treatment Outcome
17.
J Cancer ; 8(17): 3448-3455, 2017.
Article in English | MEDLINE | ID: mdl-29151928

ABSTRACT

Objective To determine the prognostic utility of serum pre-albumin in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone (AA). Patients and Methods 112 chemotherapy pretreated or chemotherapy-naive patients were scheduled for systemic treatment with AA. Serum pre-albumin levels were measured before and after 3 months of AA treatment. Univariate and multivariate analyses were performed to determine prognostic factors that were associated with PSA progression-free survival (PSA-PFS), radiographic PFS (rPFS) and overall survival (OS). The Harrell concordance index with variables only or combined pre-albumin data were used to evaluate the prognostic accuracy. Results The group of patients with baseline pre-albumin value ≥20mg/dL had a longer OS, PSA-PFS, rPFS than those with pre-albumin value <20mg/dL. Based on the values of pre-albumin before and after 3 months of AA treatment, we divided these patients into 4 groups: high-high, high-low, low-high and low-low group. High- high group showed a significantly better OS, PSA-PFS, rPFS than other 3 groups. In multivariate analysis, low pre-albumin level remained significant predictors of OS (HR, 13.2; P<0.001), rPFS (HR, 3.7; P=0.003) and PSA-PFS (HR, 8.7; P<0.001). The estimated c-index of the multivariate model for OS increased from 0.814 without pre-albumin to 0.845 when pre-albumin added. Conclusion Low pretreatment serum pre-albumin is a negative independent prognosticator of survival outcomes in mCRPC treated with AA and also increases the accuracy of established prognostic model. Serial pre-albumin evaluation might help clinicians guide clinical treatment of mCRPC patients.

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