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Prostate cancer is the most common malignancy of the male genitourinary system. In 2022, the European Association of Urology (EAU) published an update of the guidelines for prostate cancer, following the updating of evidence. The clinical application of nuclear medicine diagnostic and therapeutic techniques in the staging and grading, screening and assessment of prostate cancer, especially metastatic castration-resistant prostate cancer, is becoming more and more valuable. This article aims to introduce the application of nuclear medicine recommended in the 2022 edition of EAU guidelines for prostate cancer based on the latest clinical evidence.
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Objective:To investigate the safety and efficacy of modified Retzius-sparing robot-assisted laparoscopic radical prostatectomy for localized transitional zone prostate cancer.Methods:From May 2019 to February 2021, the clinical data of 284 patients with transitional zone(TZ) prostate cancer was retrospectively analyzed. Among them, 91 cases underwent modified Retzius-sparing robot-assisted laparoscopic radical prostatectomy(modified RS-RARP), and 193 cases underwent conventional robot-assisted laparoscopic radical prostatectomy (RARP). The Retzius space was directly entered during modified RS-RARP.The mean age of modified RS-RARP group and conventional RARP group was (67.8±9.1) years old and (69.5±8.4) years old, respectively. BMI of the two groups was (21.57±2.25)kg/m 2 and (21.8±1.8)kg/m 2 respectively; prostate volume was (31.2±13.5)ml and (29.3±12.9)ml respectively; preoperative PSA of the two groups were (10.2±6.1)ng/ml and (9.3±5.8)ng/ml respectively; and there was no significant difference in the above mentioned data( P>0.05). For Gleason score, there were 8 cases of score 6, 74 cases of score 7, 9 cases of score 8 in modified RS-RARP group and 21 cases of score 6, 153 cases of score 7, 19 cases of score 8 in conventional RARP group. For Clinical stage, there were 11 cases of T 1 stage, 80 cases of T 2 stage in modified RS-RARP group, and 20 cases of T 1 stage, 173 cases of T 2 stage in conventional RARP group. There was no significant difference in the above mentioned data( P>0.05). The operation time, intraoperative blood loss, ratio of transfusion, incidence of complication, positive rate of surgical margin and recovery of urinary continence were compared. Results:All 284 cases of surgery were completed. The operative time of modified RS-RARP was (89.2±10.1) minutes, which was significantly less than that of conventional RARP group[(100.5±12.3)min]. The intraoperative blood loss of the two groups was (245.0±50.0) ml and (250.0±50.0) ml respectively. The number of positive surgical margin was 14(15.4%) and 33(17.1%) respectively. There was no significant difference between the two groupsfor the above mentioned parameters( P>0.05). The ratio of urinary continence recovery in the modified RS-RARP group within 1 month was 49.45%, which was significantly higher than that of conventional RARP group (31.09%)( P<0.05). Conclusions:Compared with conventional RARP, modified RS-RARP might shorten the operation time and help the recovery of urinary continence for patients with TZ prostate cancer.
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Ethnicity might be associated with treatment outcomes in advanced prostate cancer. This study aimed to evaluate the efficacy and safety of androgen deprivation therapy (ADT) combined with apalutamide in East Asians with metastatic castration-sensitive prostate cancer (mCSPC). The original phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial was conducted at 260 sites in 23 countries. This subgroup analysis included patients enrolled in 62 participating centers in China, Japan, and Korea. Radiographic progression-free survival (PFS), time to prostate-specific antigen (PSA) progression, and PSA changes from baseline were compared between groups in the East Asian population. The intent-to-treat East Asian population included 111 and 110 participants in the apalutamide and placebo groups, respectively. The 24-month radiographic PFS rates were 76.1% and 52.3% in the apalutamide and placebo groups, respectively (apalutamide vs placebo: hazard ratio [HR] = 0.506; 95% confidence interval [CI], 0.302-0.849; P = 0.009). Median time to PSA progression was more favorable with apalutamide than placebo (HR = 0.210; 95% CI, 0.124-0.357; P < 0.001). Median maximum percentages of PSA decline from baseline were 99.0% and 73.9% in the apalutamide and placebo groups, respectively. The most common adverse event (AE) was rash in the apalutamide group, with a higher rate than that in the placebo group (37.3% vs 9.1%). The most common grade 3 or 4 AEs were rash (12 [10.9%]) and hypertension (12 [10.9%]) for apalutamide. The efficacy and safety of apalutamide in the East Asian subgroup of the TITAN trial are consistent with the global results.
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Humans , Male , Androgen Antagonists/adverse effects , Exanthema/chemically induced , Asia, Eastern , Prostate-Specific Antigen , Prostatic Neoplasms, Castration-Resistant/pathology , Thiohydantoins/adverse effectsABSTRACT
Castration-resistant prostate cancer (CRPC) is an important research focus in the field of prostate cancer. The adjustment of its diagnosis criteria also directly impacts the clinical diagnosis and treatment practice, as well as the design and implementation of the relevant clinical trials. The Prostate Cancer Clinical Trials Working Group (PCWG) has published several consensuses to provide further reference in clinical practice and trials design. In PCWG3, the recommended PSA cut-off value to confirmed CRPC diagnosis was further lowered from 2 ng / ml to 1 ng/ml. The update of PCWG3 may have a profound impact on the clinical diagnosis, treatment and trials design of prostate cancer in the future.
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Objective:To explore the efficacy of single-plane bi-parameter magnetic resonance imaging (bpMRI) in the diagnosis of prostate cancer.Methods:The clinical data of 343 patients who underwent transperineal template prostate magnetic resonance-transrectal ultrasound (MRI-TRUS) cognitive fusion biopsy at the First Affiliated Hospital of Nanjing Medical University from January 2020 to July 2021 were retrospectively analyzed, with median age of [65.0(59.0, 72.0)] years, median body mass index (BMI) of [24.1(22.2, 25.6)]kg/m 2, median prostate volume (PV) of [41.7(29.1, 53.3)]ml, median PSA[6.9 (5.5, 8.4) ng/ml], median PSAD of[0.17(0.12, 0.22) ng/ml 2], and abnormal rate of digital rectal examination (DRE) [6.4%(22/343)]. All patients underwent initial biopsy and bi-parameter magnetic resonance imaging (bpMRI) examination before biopsy, and the images were interpreted using prostate image reporting and data system version 2.1 (PI-RADS v2.1). The detection rates of prostate cancer and clinically significant prostate cancer (csPCa) were compared between single-plane bpMRI and bpMRI. When PI-RADS≥3 score, MRI results were positive; when PI-RADS ≤2 score, MRI results were negative. Results:In the single-plane bpMRI group, 121 MRI results were negative and 222 were positive. Positive patients included 95 with PI-RADS 3 score, 94 with PI-RADS 4 score, and 33 with PI-RADS 5 score. In bpMRI group, 141 MRI results were negative and 202 were positive. Among the positive patients, 67 patients with PI-RADS 3 score, 102 patients with PI-RADS 4 score, and 33 patients with PI-RADS 5 score. The detection rates of single-plane bpMRI and bpMRI for prostate cancer were 22.3% (27/121) and 15.6% (22/141) in MRI negative cases[22.3% (27/121) and 15.6% (22/141), P=0.17], and PI-RADS scores with 3 points [35.8% (34/95) vs. 44.8% (30/67), P=0.25], 4 points [89.4% (84/94)vs. 90.2% (92/102), P=0.85] and 5 points [90.9% (30/33) vs. 93.9% (31/33), P=1.00] showed no significant difference in stratification. The detection rate of csPCa in the single-plane bpMRI group and bpMRI group was significantly different in the MRI negative cases [7.4% (9/121) and 2.1% (3/141), P=0.04]. PI-RADS scores with 3 points [22.1% (21/95) vs. 29.9% (20/67), P=0.27], 4 points [80.9% (76/94) vs. 79.4% (81/102), P=0.80] and 5 points [84.9% (28/33) vs. 90.9% (30/33), P=0.71] showed no significant difference in stratification. Conclusions:For those suspected of prostate cancer patients with PSA 4-10 ng/ml and PI-RADS score ≥3, single-plane bpMRI or bpMRI examination has the same efficacy in term of the detection rate of prostate cancer and csPCa.
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Objective:To optimize the preparation conditions and methods of Al 18F-prostate specific membrane antigen (PSMA)-11 and evaluate the feasibility of clinical transformation. Methods:PSMA- N, N′-bis(2-hydroxy-5-(carboxyethy)benzyl)ethylenediamine- N, N′-diacetic acid (HBED-CC) dissolved in CH 3COONH 4 buffer (pH=4.8) was reacted with AlCl 3·3H 2O dissolved in pure water at a molar ratio of 1∶1 (60 ℃, 10 min), and then purified by tC18 column and freeze-dried to obtain [Al]-PSMA-11. [Al]-PSMA-11 was labeled by 18F - and the effects of reaction temperature and pH value on the labeling rate were investigated. The labeled products were purified by tC18 column and filtered through sterile filter to obtain Al 18F-PSMA-11. The comparison of biodistribution between Al 18F-PSMA-11 and 68Ga-PSMA-11 was analyzed on 5 healthy volunteers (age (56±8) years). The differences of SUV max between two groups were analyzed by independent-sample t test. Besides, the early and delayed imaging of Al 18F-PSMA-11 PET/CT were performed on a patient (70 years old) with recurrent prostate cancer for assessment of its potential for prostate cancer recurrence monitoring. Results:The labeling rate was (42.3±3.2)% reacting in aqueous phase (60 ℃, pH=4.8) for 15 min. After being purified with tC18 cartridge, the radiochemical purity of the product was still more than 95% after placement at room temperature for 3 h. Preliminary application demonstrated that there was no significant difference in the biodistribution of Al 18F-PSMA-11 and 68Ga-PSMA-11 among lacrimal gland, parotid gland, submandibular gland, liver, spleen, kidney, bladder and part of intestine and SUV max of targeted organs were also not different ( t values: 0.19-1.95, all P>0.05) between two groups. Multiple bone metastases were observed by Al 18F-PSMA-11 PET/CT delayed imaging (3 h) in a patient with recurrent prostate cancer. Conclusion:Al 18F-PSMA-11 produced with pre-conjugated [Al]-PSMA-11 meets the requirement of the PET imaging application, and it has good potential of localization and imaging for prostate cancer metastatic lesions.
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Objective:Apt-A10-3.2 (aptamer of prostate specific membrane antigen (PSMA)) can be used as a specific ligand for early diagnosis and targeted treatment of prostate cancer. Mouse double minute 2 homolog (MDM2) is closely related to the malignancy of prostate cancer, and MDM2 small interfering RNA (siRNA) can silence MDM2 gene through RNA interference. To design a novel chimera of PSMA Apt-MDM2 siRNA and combine it with docetaxel (DTX) to explore a new diagnosis and treatment model combining targeted therapy of PSMA-positive prostate cancer with 99Tc m-chimera imaging monitoring. Methods:Apt-siRNA were obtained by covalent connection of PSMA Apt-A10-3.2 and MDM2 siRNA, which was combined with DTX to treat PSMA-positive prostate cancer cell lines (22RV1 and LNCaP). Cell lines were treated with Apt-siRNA alone or in combination with DTX. The levels of MDM2 and apoptosis-related proteins (B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), poly ADP-ribose polymerase (PARP), caspase-3) were detected by Western blot, which were used to evaluate the therapeutic effect. Fifteen BALB/c mice bearing 22RV1 xenografts were treated with PBS, DTX+ Apt-siRNA (200 pmol) and DTX+ Apt-siRNA (400 pmol), respectively. Tumor volume and MDM2 level were observed, and 99Tc m-Apt-siRNA SPECT imaging was performed to obtain the tumor/muscle (T/M) ratio. One-way analysis of variance, Tukey′s test and linear regression analysis were used for data analysis. Results:The levels of MDM2 protein were significantly decreased by Apt-siRNA (0.25±0.02, F=183.40, P<0.001; 0.56±0.03, F=37.15, P<0.001) in 22RV1 and LNCaP cells. After the treatment of Apt-siRNA+ DTX, the levels of Bcl-2 were significantly decreased, and the levels of Bax, PARP and caspase-3 were significantly increased. MDM2 protein level (400 pmol: 0.59±0.12; F=49.99, P=0.023) and tumor volume (400 pmol: (0.22±0.07) cm 3;F=71.30, P=0.039) were significantly inhibited by Apt-siRNA+ DTX in mice bearing 22RV1 xenografts. As for 99Tc m-Apt-siRNA SPECT imaging in vivo, T/M ratio of treatment group was significantly decreased (400 pmol: 2.07±0.22; F=34.99, P=0.022), and there was a linear regression relationship between T/M ratio and the expression level of MDM2 ( R2=0.875, P<0.001). Conclusion:Apt-siRNA combined with DTX can effectively inhibit the progression of prostate cancer, and realize visual targeted diagnosis and treatment of PSMA-positive prostate cancer by coupling radionuclide technetium.
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To improve the diagnostic efficiency of prostate cancer (PCa) and reduce unnecessary biopsies, we defined and analyzed the diagnostic efficiency of peripheral zone prostate-specific antigen (PSA) density (PZ-PSAD). Patients who underwent systematic 12-core prostate biopsies in Shanghai General Hospital (Shanghai, China) between January 2012 and January 2018 were retrospectively identified (n = 529). Another group of patients with benign prostatic hyperplasia (n = 100) were randomly preselected to obtain the PSA density of the non-PCa cohort (N-PSAD). Prostate volumes and transition zone volumes were measured using multiparameter magnetic resonance imaging (mpMRI) and were combined with PSA and N-PSAD to obtain the PZ-PSAD from a specific algorithm. Receiver operating characteristic (ROC) curve analysis was used to assess the PCa detection efficiency in patients stratified by PSA level, and the area under the ROC curve (AUC) of PZ-PSAD was higher than that of PSA, PSA density (PSAD), and transition zone PSA density (TZ-PSAD). PZ-PSAD could amend the diagnosis for more than half of the patients with inaccurate transrectal ultrasonography (TRUS) and mpMRI results. When TRUS and mpMRI findings were ambiguous to predict PCa (PIRADS score ≤3), PZ-PSAD could increase the positive rate of biopsy from 21.7% to 54.7%, and help 63.8% (150/235) of patients avoid unnecessary prostate biopsy. In patients whose PSA was 4.0-10.0 ng ml
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Introduction: The androgen receptor (AR) plays an important role in normal development of the prostate gland, as well as in prostatic neoplasms. Transcriptional regulation by AR is modulated by its interaction with co-activators or co-repressors, such as NCoR1 (nuclear receptor co-repressor 1), which is involved in reducing AR activity over the target gene transcription. Methods: To identify the role of NCoR1 in the prostate cancer androgen independence in a cell line model, we aimed to evaluate the effects of silencing NCoR1 on prostate-specific antigen (PSA) gene expression, the proliferative response and PSA secretion on the supernatant of C4-2B and LNCaP cells that were submitted to small interfering RNAs (siRNAs) transfection, and to treatments with different androgen dosages. Results: In LNCaP and C4-2B cells with no dihydrotestosterone (DHT) treatment, a decrease in PSA mRNA expression was observed 48 hours and 72 hours after gene silencing in the siNCoR group when compared to the control and siNC groups. The LNCaP and C4-2B cells showed a biphasic pattern in response to dihydrotestosterone treatment in transfected groups (siNCoR and siNC) as well as in the control condition (without transfection). The secretion of PSA in cell supernatant of LNCaP and C4-2B cells was higher in the siNCoR group, and, in relation to hormonal treatment, higher in the 10-8 M DHT group. Conclusions: A reduction in the NCoR1 levels seems to have a double influence on the activity of AR in PCa cells. These results suggest that NCoR may act as an AR co-repressor depending upon hormonal stimulation.(AU)
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Humans , Male , Prostatic Neoplasms , Prostate-Specific Antigen , Cell Proliferation , Nuclear Receptor Co-Repressor 1 , Dihydrotestosterone , Receptors, Androgen , Cell Line , Co-Repressor ProteinsABSTRACT
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Humans , Male , Antineoplastic Agents , Cardiovascular Diseases , Cohort Studies , Comorbidity , Diagnosis , Drug Therapy , Follow-Up Studies , Gonadotropin-Releasing Hormone , Incidence , Morinda , Multivariate Analysis , Myocardial Ischemia , National Health Programs , Observational Study , Passive Cutaneous Anaphylaxis , Prostate , Prostatic Neoplasms , Social ClassABSTRACT
Hypoxia-induced erythropoietin signaling plays an important role in tumor growth and invasion. In the present study, we investigated the contribution of erythropoietin signaling pathway to castration-resistant prostate cancer and the development of a neuroendocrine phenotype. Immunohistochemical staining showed that the erythropoietin and erythropoietin receptor scores in castration-resistant prostate cancer and androgen-dependent prostate cancer were 7.55 versus 4.5 and 7.45 versus 5.9,respectively (P < 0.001). Furthermore, a cell proliferation assay was conducted, and the differential expression of erythropoietin and erythropoietin receptor in LNCaP cells and hypoxia-induced LNCaP cells was evaluated using western blot and quantitative real-time PCR. The proliferation capacity of hypoxia-induced LNCaP cells was similar in cultures of both fetal bovine serum and charcoal-stripped fetal bovine serum, suggesting that LNCaP cells acquired hypoxia-induced androgen-independent growth. After 2 weeks of hypoxic culture, LNCaP cells showed a neuroendocrine cell change and increased expression of neuron-specific enolase, erythropoietin, and erythropoietin receptor; knockdown of erythropoietin receptor reversed the hypoxia-induced upregulation of neuron-specific enolase in the LNCaP cells. In conclusion, the concurrent upregulation of erythropoietin and erythropoietin receptor in castration-resistant prostate cancer suggests that the erythropoietin/erythropoietin receptor autocrine loop plays an important role in the progression of castration resistance and is responsible for the development of a neuroendocrine phenotype.
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PURPOSE: This study was conducted to identify the differences in symptoms, depression, intimacy and quality of life (QOL), and the factors influencing QOL in men with prostate cancer undergoing androgen deprivation therapy (ADT). METHODS: This study used a cross-sectional, descriptive research design. Data were collected using a self-report questionnaire from 122 men with prostate cancer undergoing ADT. The data collection period was from November 19, 2018 to February 25, 2019. Data were analyzed using t-tests, χ2 tests, Fisher's exact tests, 4-way ANOVA and multiple regression. RESULTS: The mean age of the men was 70.3±7.3. There were statistically significant differences in urinary, bowel, sexual and hormonal symptoms according to treatment duration (F=23.74, p<.001). Factors influencing QOL explained 55% of the variance (adjusted R2=.55, p<.001). These factors were depression (β=−.52, p<.001), intimacy (β=.23, p=.001), ADT duration (β=−.17, p=.011), economic status middle (β=.23, p=.006), high (β=.29, p=.001) and sleep (β=.15, p=.023). CONCLUSION: The study found an association between ADT duration and symptoms, and the factors influencing QOL of participants. It provides a base for future research direction on ADT and patient QOL.
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Humans , Male , Data Collection , Depression , Hormone Replacement Therapy , Prostate , Prostatic Neoplasms , Quality of Life , Research DesignABSTRACT
PURPOSE: To compare biopsy performance of 2 approaches for multiparametric magnetic resonance imaging (MRI) guided biopsy and transrectal ultrasonography (TRUS)-guided biopsy with 2nd and 3rd repeat biopsy patients in prostate cancer detection. MATERIALS AND METHODS: This retrospective study reviewed 2,868 patients who was performed prostate biopsy between September 2013 to March 2017 at Samsung Medical Center, Seoul, Korea with TRUS-guided random biopsy and MRI fusion, MRI cognitive, and MRI-guided biopsy as 2nd and 3rd repeat biopsy and propensity matching was applied to reduce bias. Detection rate of each study was compared with 1:1 matching. RESULTS: Among 265 patients who performed TRUS 2nd biopsy, positivity rate for prostate cancer (PCa) was 18.49% (n=49/265) while 54.72% (n=145/265) for MRI-guided biopsy. In 3rd biopsy, positivity rate for PCa of TRUS biopsy was 17.74% (n=11/62) while 56.45% (n=35/62) for MRI guided biopsy. There was no significant difference in the detection rate for the patient with Gleason score 8 or more. CONCLUSIONS: MRI-guided biopsy was associated with a higher detection rate of prostate cancer with especially in patients with prior negative biopsy.
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Humans , Bias , Biopsy , Cohort Studies , Korea , Magnetic Resonance Imaging , Neoplasm Grading , Passive Cutaneous Anaphylaxis , Propensity Score , Prostate , Prostatic Neoplasms , Retrospective Studies , Seoul , UltrasonographyABSTRACT
Summary Objective: Considering the importance of screening for prostate cancer, the possibility of damage resulting from indiscriminate screening and the difficulty of disclosure and adherence to the main guidelines on the subject, we aimed to identify current guidelines, look for common approaches and establish a core of conducts. Method: Systematic review of the literature on screening practice guidelines for prostate cancer searching the databases PubMed, Lilacs and Google Scholar and active search in the sites of several national health entities. Results: Twelve (12) guidelines were selected, whose analysis resulted in the identification of six common points of conduct, with the following minimum core of recommendations: (1) screening indication or not: must be individualized, and preceded by an informed decision; (2) tests used: PSA with or without rectal digital examination; (3) age at which initiate testing in men in general risk: 50-55 years; (4) age at which to initiate testing in men at increased risk: 40-45 years; (5) the interval between screening: annual or biennial; and (6) age at which to discontinue testing: 70 years-old or life expectancy less than 10 years. Conclusion: Although there are differences between them, it was possible to establish a minimum core of conducts that may be useful in the daily practice of the physician.
Resumo Objetivo: Considerando a importância do rastreamento de câncer de próstata, a possibilidade de dano decorrente do rastreamento indiscriminado, a dificuldade de divulgação e adesão às diretrizes sobre o assunto, objetivamos identificar as principais diretrizes vigentes, procurar pontos de abordagem comuns e estabelecer um núcleo mínimo de condutas. Método: Revisão sistemática da literatura sobre guias de prática de rastreamento para câncer de próstata nas bases Pubmed, Lilacs e Google Scholar, além de busca ativa nos sítios de diversas entidades de saúde nacionais. Resultados: Foram selecionadas 12 diretrizes, cuja análise resultou na identificação de seis pontos comuns de conduta, com o seguinte núcleo mínimo de recomendações: (1) a indicação ou não de rastreamento: deve ser individualizada e precedida de uma decisão informada; (2) os exames utilizados: PSA com ou sem exame digital retal; (3) a idade de início geral: 50-55 anos; (4) a idade de início em homens com risco aumentado: 40 anos; (5) o intervalo entre os rastreamentos: anual ou bienal; e (6) a idade de suspensão do rastreamento: 70 anos ou expectativa de vida menor que 10 anos. Conclusão: Embora existam divergências entre elas, foi possível estabelecer um núcleo mínimo de condutas que podem ser úteis na prática diária do médico.
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Humans , Male , Prostatic Neoplasms/diagnosis , Mass Screening/standards , Practice Guidelines as Topic , Early Detection of Cancer/standards , Prostate-Specific Antigen/standards , Age of OnsetABSTRACT
PURPOSE: Fibroblast growth factor (FGF) signals are important in carcinogenesis and progression of prostate cancer. Dovitinib is an oral, pan-class inhibitor of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, and fibroblast growth factor receptor (FGFR). We evaluated the efficacy and toxicity of dovitinib in men with metastatic castration resistant prostate cancer (mCRPC). MATERIALS AND METHODS: This study was a single-arm, phase II, open-label, multicenter trial of dovitinib 500 mg/day (5-days-on/2-days-off schedule). The primary endpoint was 16-week progression-free survival (PFS). Secondary endpoints were overall survival (OS), toxicity and prostate-specific antigen (PSA) response rate. Biomarker analyses for VEGFR2, FGF23, and FGFR2 using multiplex enzyme-linked immunosorbent assay was performed. RESULTS: Forty-four men were accrued from 11 hospitals. Eighty percent were post-docetaxel. Median PSA was 100 ng/dL, median age was 69, 82% had bone metastases, and 23% had liver metastases. Median cycles of dovitinib was 2 (range, 0 to 33). Median PFS was 3.67 months (95% confidence interval [CI], 1.36 to 5.98) and median OS was 13.70 months (95% CI, 0 to 27.41). Chemotherapy-naïve patients had longer PFS (17.90 months; 95% CI, 9.23 to 28.57) compared with docetaxel-treated patients (2.07 months; 95% CI, 1.73 to 2.41; p=0.001) and the patients with high serum VEGFR2 level over median level (7,800 pg/mL) showed longer PFS compared with others (6.03 months [95% CI, 4.26 to 7.80] vs. 1.97 months [95% CI, 1.79 to 2.15], p=0.023). Grade 3 related adverse events were seen in 40.9% of patients. Grade 1-2 nausea, diarrhea, fatigue, anorexia, and all grade thrombocytopenia are common. CONCLUSION: Dovitinib showed modest antitumor activity with manageable toxicities in men with mCRPC. Especially, patients who were chemo-naïve benefitted from dovitinib.
Subject(s)
Humans , Male , Anorexia , Biomarkers , Carcinogenesis , Castration , Diarrhea , Disease-Free Survival , Enzyme-Linked Immunosorbent Assay , Fatigue , Fibroblast Growth Factors , Liver , Multicenter Studies as Topic , Nausea , Neoplasm Metastasis , Prostate , Prostate-Specific Antigen , Prostatic Neoplasms , Prostatic Neoplasms, Castration-Resistant , Receptors, Fibroblast Growth Factor , Receptors, Platelet-Derived Growth Factor , Receptors, Vascular Endothelial Growth Factor , ThrombocytopeniaABSTRACT
Resumo Recentemente, inúmeras campanhas nacionais promovidas por hospitais, sociedades médicas e outras organizações têm estimulado o rastreamento do câncer de próstata, em consonância com iniciativas mundiais conhecidas como Novembro Azul. Essas campanhas aconselham a utilização do toque retal acompanhado da dosagem sérica do antígeno prostático específico em faixas etárias definidas. A motivação seria a detecção precoce da neoplasia, com redução de sua mortalidade e das complicações e impactos associados ao seu tratamento. A dosagem do PSA para fins de rastreamento é alvo de grande controvérsia, visto que a maioria dos tumores detectados pelo rastreamento é de evolução lenta e não interfeririam na sobrevida ou na qualidade de vida do paciente. O rastreamento de base populacional não é a indicação de inúmeras instituições estrangeiras e, no Brasil, o Instituto Nacional de Câncer também não recomenda à organização programas de rastreamento desse tipo. O artigo discute os riscos e benefícios associados a esse tipo de estratégia e reforça a preocupação com o uso inadequado e indiscriminado do rastreamento para o câncer de próstata.
Abstract Recently, numerous national campaigns promoted by hospitals, medical societies and other organizations have stimulated prostate cancer screening, in line with worldwide initiatives known as Blue November. These campaigns advise the use of rectal examination accompanied by dosage of serum prostate specific antigen (PSA) levels in defined age groups. The motivation would be the early detection of neoplasia, with reduction of mortality and complications and impacts associated with its treatment. The PSA dosage for screening purposes is highly controversial, since most of such tumors detected by screening are of slow progression and would not interfere with patient survival or quality of life. Population-based screening for prostate cancer is not recommended by numerous foreign institutions, including the National Cancer Institute in Brazil. The article discusses the risks and benefits associated with this type of strategy and reinforces concern about the inappropriate and indiscriminate use of screening for prostate cancer.
Subject(s)
Humans , Male , Prostatic Neoplasms/diagnosis , Quality of Life , Survival , Mass Screening/adverse effects , Mortality , Prostate-Specific Antigen , Evidence-Based Medicine , Men's Health/trends , Early Detection of Cancer/trendsABSTRACT
Objective To explore risk factors of the progression to castration-resistant prostate cancer(CRPC)after hormone therapy (HT).Methods A total of 178 patients with prostate cancer from February 2009 to February 2018 were enrolled to analyze the risk factors of the progression to castrationresistant prostate cancer after androgen deprivation therapy in Fujian Medical University Union Hospital.The mean age was72 years (range,49-91 years);the middle Gleason score was 7 (range,4-10);the middle PSA at the initiation of HT was 24.45 ng/ml (range,0.16-100.0 ng/ml);the middle time to PSA nadir was 9 months (range,0.5-69.0 months);the middle PSA nadir after HT was 0.030 ng/ml (range,0.003-78.670 ng/ml);the mean hemoglobin level was 131 g/L (range,64-184 g/L);the mean alkaline phosphatase level was 98 U/L (range,35-734 U/L);39 patients were diabetes mellitus (21.9％);82 patients were bone metastasis/visceral metastasis (46.1％);85 patients (47.8 ％) were in clinical T1 + T2;93 patients(52.2％)were in clinical T3 + T4.We studied the relationship between CRPC and these risk factors including age,Gleason score,PSA at the initiation of HT,PSA nadir after HT,the time to PSA nadir,hemoglobin level,alkaline phosphatase,bone metastasis/visceral metastasis,clinical T stage,diabetes mellitus by x2 test,univariate and multivariate Cox regression analysis methods.Results The middle follow-up time was 30 months (range,6-92 months).There were 74 of 178 patients progressed to CRPC after HT.The median time of progression to CRPC in this cohort was 15 months (range,4-47 months).On x2 test analysis,there were statistically significant differences between the progression to CRPC group after HT and the rest group in Gleason score (P ＜0.001),PSA nadir after HT (P ＜0.001),PSA at the initiation of HT (P =0.042),alkaline phosphatase (P =0.002),bone metastasis/visceral metastasis (P＜0.001) and clinical T stage (P ＜0.001).Additionally,on multivariate Cox regression analysis,Gleason score (OR =6.152,P ＜ 0.001),PSA nadir after HT (OR =3.022,P ＜ 0.004) and the time to PSA nadir (OR =0.375,P ＜0.001) were found to be significantly associated with the rapid progression to CRPC.Conelusions Gleason score,PSA nadir after HT and the time to PSA nadir were significantly associated with the progression to CRPC.Patients with higher PSA nadir or the shorter time to PSA nadir were more likely to progress to CRPC.
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Objective To analyze the clinical and pathological characteristics and prognosis of stage pT0 prostate cancer patients after radical prostatectomy.Methods From November 2004 to May 2017,eight patients who underwent radical prostatectomy and postoperatively diagnosed with pT0 were retrospectively evaluated.The patients aged 63-75 years (mean 69.1 years),with PSA 2.26-14.10 ng/ml(mean 6.10 ng/ml),prostate volume 30.3-72.1 ml (mean 52.1 ml).Exclusion criteria included patients undergoing neoadjuvant hormone therapy or TURP before the operation.Stage pT0 prostate cancer was defined as no evidence of residual tumor in radical prostatectomy specimen from the patient in whom biopsy-proven prostate carcinoma was histologically diagnosed.The clinical and pathological data were reviewed and follow-up was performed for stage pT0 prostate cancer patients.Biochemical progression was defined as postoperative PSA greater than 2 ng/ml for twice.The patients were followed-up.Results Eight patients (1.1％) were postoperatively diagnosed with prostate cancer of pT0 stage.After radical prostatectomy specimen was reexamined by an uropathological expert,small residual tumor(2mm) was found in left peripheral zone of the prostate in one patient.The average follow-up duration was 75 months for this 8 pT0 patients.One patient died of pulmonary embolism after 5 days of the surgery.No patient had evidence of biochemical progression.No biochemical recurrence survival rate and cancer-specific survival rate was 100％ (7/7) and overall survival rate was 87.5％ (7/8) for pT0 prostate cancer patients.Conclusions For patients who were biopsy-proven prostate cancer without neoadjuvant hormone therapy,stage pT0 was a rare pathological phenomenon.Those patients had a very favourable oncological prognosis.
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Objective To evaluate the prognostic value of the ratio of AR and AR-V7 expression in prostate cancer treated by castration therapy.Methods Immunohistochemical staining was performed in biopsy specimen of 136 prostate cancer patients received hormone therapy in Tongji Hospital of Huazhong University of Science and Technology from January 2010 to December 2015.Expression was determined using modified H score method.Patients aged from 53-96,the median age was 71,median tPSA value at diagnosed was 110.00 ng/ml(2.61-4 003.4 ng/ml),median fPSA value was 14.62 ng/ml(0.12-640.19 ng/ml),median PSA density was 1.15 ng/(ml · cm3) [0.02-62.63 ng/(ml · cm3)].Among these,88 (64.7％)patients were diagnosed Gleason score≥8,39(28.7％) patients with Gleason score 7,while 7 (6.6％) patients Gleason score ＜7.There were 54(39.7％) patients diagnosed T4 stage,57(41.9％)patients T3 stage and 25 (18.4％) patients Tx stage;62 (45.6％) patients were diagnosed N 1 stage,46 (33.8％) N0 stage and 28(20.6％) patients Nx stage;97(71.3％) patients were diagnosed M1 stage,30(22.1％) M0 stage,9 (6.6％) patients Mx stage.Cause-specific Cox regression and Kaplan-Meier Analysis were used to analyze the prognosis risk.Results The median follow-up time was 44 months,ranged 15-71 months.During the surveillance,the disease progression-free survival time ranged from 5-59 month,median 19 months.The overall survival time ranged from 12-61 months,median 31 months.Among these,79(58.1％) patients were AR positive and 26(19.1％) patients were AR-V7 positive,while AR and AR-V7 expression had no significant correlation (Spearman-test r =0.042,P =0.629).The AR-V7 positive patients showed significantly lower CRPC progression free survival (10.8 months vs.25.0 months,P ＜ 0.001) and much lower overall survival (20.3 months vs.42.8 months,P ＜ 0.001).The high AR-V7/AR expression ratio group showed significantly lower CRPC progression free survival (12.0 months vs.24.8 months,P ＜ 0.001) and much lower overall survival (22.5 months vs.42.8 months,P ＜ 0.001).In univariate Cox regression analyses,Gleason score at diagnosis,T stage,tPSA,PSA density and high AR-V7/AR expression ratio could predict the prognosis of hormonal therapy.While in multivariate Cox regression analyses,T stage(HR =2.597,95％ CI 1.351-4.995,P =0.004) and high AR-V7/AR expression ratio(HR =5.788,95％ CI 2.530-13.242,P ＜ 0.001) could effectively and independently predict the prognosis of hormonal therapy.Conclusion High AR-V7/AR HS ratio is the independent predictor of the prognosis of prostate cancer hormone therapy.AR-V7 positive and high AR-V7/AR HS ratio patients may have shorter PFS and overall survival time than AR-V7 negative and low AR-V7/AR HS ratio patients.
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Historically, testosterone and prostate cancer have been demonstrated to have a positive association leading providers to forgo testosterone replacement therapy (TRT) in men with concurrent histories of hypogonadism and prostate cancer. This paradigm has been gradually shifting with our evolving understanding of the relationship between testosterone and prostate cancer and the gaining popularity of the saturation model. Newer data suggests improved quality of life for men with hypogonadism after TRT leading to a more tempered view of the effects of this treatment and its risk in prostate cancer. As more reports emerge of TRT in men who have either undergone definitive treatment for prostate cancer or are on active surveillance, some providers see a role for TRT in these patients despite non-consensus in clinical guidelines. It is critical that we examine evidence currently available, while we await more rigorous data to emerge.