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1.
Journal of Zhejiang University. Medical sciences ; (6): 133-138, 2023.
Article in English | WPRIM | ID: wpr-982027

ABSTRACT

OBJECTIVES@#To investigate the prevalence of pathogenic germline mutations of mismatch repair (MMR) genes in prostate cancer patients and its relationship with clinicopathological characteristics.@*METHODS@#Germline sequencing data of 855 prostate cancer patients admitted in Fudan University Shanghai Cancer Center from 2018 to 2022 were retrospectively analyzed. The pathogenicity of mutations was assessed according to the American College of Medical Genetics and Genomics (ACMG) standard guideline, Clinvar and Intervar databases. The clinicopathological characteristics and responses to castration treatment were compared among patients with MMR gene mutation (MMR+ group), patients with DNA damage repair (DDR) gene germline pathogenic mutation without MMR gene (DDR+MMR- group) and patients without DDR gene germline pathogenic mutation (DDR- group).@*RESULTS@#Thirteen (1.52%) MMR+ patients were identified in 855 prostate cancer patients, including 1 case with MLH1 gene mutation, 6 cases with MSH2 gene mutation, 4 cases with MSH6 gene mutation and 2 cases with PMS2 gene mutation. 105 (11.9%) patients were identified as DDR gene positive (except MMR gene), and 737 (86.2%) patients were DDR gene negative. Compared with DDR- group, MMR+ group had lower age of onset (P<0.05) and initial prostate-specific antigen (PSA) (P<0.01), while no significant differences were found between the two groups in Gleason score and TMN staging (both P>0.05). The median time to castration resistance was 8 months (95%CI: 6 months-not achieved), 16 months (95%CI: 12-32 months) and 24 months (95%CI: 21-27 months) for MMR+ group, DDR+MMR- group and DDR- group, respectively. The time to castration resistance in MMR+ group was significantly shorter than that in DDR+MMR- group and DDR- group (both P<0.01), while there was no significant difference between DDR+MMR- group and DDR- group (P>0.05).@*CONCLUSIONS@#MMR gene mutation testing is recommended for prostate cancer patients with early onset, low initial PSA, metastasis or early resistance to castration therapy.


Subject(s)
Male , Humans , Prostate-Specific Antigen/genetics , Germ-Line Mutation , Retrospective Studies , DNA Mismatch Repair/genetics , DNA-Binding Proteins/metabolism , China , Prostatic Neoplasms/pathology
2.
Chinese Medical Journal ; (24): 1207-1215, 2023.
Article in English | WPRIM | ID: wpr-980845

ABSTRACT

BACKGROUND@#LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer.@*METHODS@#We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels.@*RESULTS@#On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]).@*CONCLUSION@#LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile.@*TRIAL REGISTRATION@#ClinicalTrials.gov, NCT04563936.


Subject(s)
Humans , Male , Antineoplastic Agents, Hormonal/therapeutic use , East Asian People , Gonadotropin-Releasing Hormone/agonists , Goserelin/therapeutic use , Prostate-Specific Antigen , Prostatic Neoplasms/drug therapy , Testosterone
3.
Chinese Journal of Urology ; (12): 535-539, 2022.
Article in Chinese | WPRIM | ID: wpr-957423

ABSTRACT

Objective:To observe the efficacy and safety of radium-223 in metastatic castration resistant prostate cancer (mCRPC) with bone metastasis.Methods:The clinical data of 48 patients with mCRPC treated with radium-223(55 kBq/kg, once every 4 weeks, planned to use for 6 cycles)from February 2021 to May 2022 were analyzed retrospectively. All patients had symptomatic bone metastasis without visceral metastasis, which the number of bone metastasis was more than one site.They were all classified as IVb stage. The average age was 70.5 (ranging 49-90) years. The median PSA was 44.70(ranging 0.15-1 864.00) ng/ml. The median ALP was 162 (ranging 43-1 589) U/L. The median time from mCRPC diagnosis to radium-223 use was 10 (ranging 3-47) months. 9, 18 and 11 patients had received first-line, second-line and third-line treatment for mCRPC before enrollment respectively, 10 patients had received at least fourth-line treatment. 38 (79.1%), 31 (64.5%), 30 (62.5%) and 7 (14.6%) patients had used abiraterone, enzalutamide, docetaxel and olaparib before enrollment. The probability of PSA level decrease >30%, ALP level decrease >30%, symptom improvement rate, median overall survival (OS), as well as the occurrence of treatment-related adverse reactions and the reasons for withdraw treatment were analyzed.Results:The median follow-up time was 8 (ranging 1-16) months. 11 patients completed all 6 courses of treatment. The median number of completed courses was 4 (ranging 1-6). 27 patients (56.2%) received radium-223 and bone protection drugs (Bisphosphate/ Denosumab). PSA decreased by >30% was recorded in 10 patients (20.8%) and ALP decreased by >30% was recorded in 25 patients (52.1%). 23 cases (47.9%) reported bone pain relief during treatment. Among the 9 patients who had received first-line of mCRPC previously, 6 cases (66%) had relief of bone pain symptoms, and 4 cases (44%) had a decrease of PSA >30%. Among the 18 patients who had previously received second-line mCRPC treatment, 11 cases (61%) had relief of bone pain symptoms, and 4 cases (22%) had a decrease of PSA >30%. Among the 21 patients who had received third-line or more mCRPC treatment in the past, 6 (28.5%) had symptom relief, and 2 (9.5%) had PSA decrease >30%. The median overall survival (OS) was not reached, and the OS was estimated to be 12.5 months using the Kaplan-Meier method. The most common hematological adverse effects were thrombocytopenia (15 cases, 31.2%; grade 3 in 6 cases and grade 4 in 0), followed by leucopenia (11 cases, 22.9%; grade 3 in 4 cases and grade 4 in 1 case) and anemia (8 cases, 16.7%; grade 3 in 3 cases and grade 4 in 0). Non-hematological adverse reactions included fever in 1 case (2.1%), constipation in 4 cases (8.3%), nausea and vomiting in 10 cases (20.8%), diarrhea in 7 cases (14.6%), dizziness in 1 case (2.1%) and fatigue in 11 cases (22.9%). Seven cases were discontinued due to intolerable adverse reactions (median 2 courses), 14 cases were discontinued due to disease progression or death (median 2 courses), and 5 cases were discontinued due to other reasons (median 1 course).Conclusions:Radium-223 has a good performance in symptom control for mCRPC patients who have previously received first-line or second-line therapy. Due to the high incidence of hematological adverse reactions, more attention should be paid to the changes of hemogram during the treatment, and timely treatment should be carried out to improve the drug tolerance of patients.

4.
Chinese Journal of Urology ; (12): 529-534, 2022.
Article in Chinese | WPRIM | ID: wpr-957422

ABSTRACT

Objective:To explore the value of gonadotropin-releasing hormone (GnRH) antagonist in prostate cancer management.Methods:We retrospectively analyzed the data of 92 consecutive hormonal sensitive prostate cancer (HSPC) patients treated with GnRH antagonist from Jan 2019 to March 2022 in Fudan University Shanghai Cancer Center. The median (IQR) age at diagnosis was 70(65-76)years old. Median(IQR) serum prostate-specific antigen (PSA) level before treatment was 98.30 (32.50-436.75)ng/ml. The median (IQR) testosterone level was 12.30(1.51-18.44)nmol/L. Twenty-six(28.3%)cases were in M 0 stage, while 66(71.7%) were in M 1 stage at diagnosis. There were 67(72.8%)cases in ≥T 3 stage, and 54(58.7%)cases in N 1 stage.The Gleason score of 80(87.0%)cases was ≥8.The second generation androgen inhibitor was used in 58(63.0%)cases, and 21(22.8%)cases had specific gene mutation. Patients received a subcutaneously 240mg Degarelix in the first 28 days and 80 mg Degarelix following every 28 days. The pre-injection and 3 months post injection PSA and testosterone (T) level were collected. According to the proportion of patients with the largest decrease in PSA, the patients were divided into high response group (PSA decrease ≥99% after 3 months of use of Degarelix) and low response group (PSA decrease <99% after 3 months of use of Degarelix). Univariate and multivariate logistic analysis were used to analyze the risk factors affecting the treatment response of Degarelix. Results:Among the 92 prostate cancer patients, after 3 months Degarelix treatment, the median PSA value decreased to 0.64ng/ ml ( P <0.001), and the median testosterone value decreased to 0.45nmol/L ( P <0.001). After treatment, there were 48 cases in the high reaction group and 44 cases in the low reaction group. Before treatment, the median PSA in the high-response group was 100.00(67.11-444.25) ng/ml, higher than 88.50 (9.91-582.25) ng/ml in the low-response group, but not statistically significant ( P=0.077). The median testosterone level in the high response group was 13.82 (7.53-19.43) nmol/L, which was significantly higher than that in the low response group [4.61 (0.75-16.12) nmol/L, P =0.030]. After treatment, the median PSA in the high-response group was 0.22 (0.09-0.82) ng/ml, significantly lower than that in the low-response group [3.22 (0.19-15.88) ng/ ml, P<0.001]. The median testosterone value of the high reaction group was 0.40 (0.09-0.80) nmol/L and that of the low reaction group was 0.45 (0.02-0.65) nmol/L, which showed no significant difference ( P =0.826), and both reached the level of castration (<1.7nmol/L). Univariate analysis showed that age ≤ 65 years old was a good prognostic factor ( OR=0.333, 95% CI 0.119-0.810, P =0.017); T stage ( P =0.540), N stage ( P =0.363), M stage ( P =0.660), Gleason score ( P =0.834), application of second-generation antiandrogens ( P=0.238) and gene mutation ( P =0.525) were not related to Degarelix hyperresponsiveness. In multivariate analysis, age was the only independent favorite prognostic factors( OR=0.913, 95% CI 0.847-0.983, P=0.016). Conclusions:In the real world, GnRH antagonists significantly reduced the levels of testosterone and PSA in HSPC patients after 3 months of treatment regardless of TNM stage, Gleason score, and the second generation androgen inhibitor using.

5.
Chinese Journal of Urology ; (12): 512-517, 2022.
Article in Chinese | WPRIM | ID: wpr-957419

ABSTRACT

Objective:To analyze germline genetic testing in Chinese high-to very-high-risk non-metastatic prostate cancer patients.Methods:This study included 249 Chinese patients with high- to very-high-risk non-metastatic prostate cancer for germline genetic testing, in Fudan University Shanghai Cancer Center, West China Hospital and Cancer Center of Sun Yat-sen University, from January 2018 to December 2022. High risk and very-high risk are termed according to National Comprehensive Cancer Network (NCCN) Prostate Cancer Guideline (2022 V1). The mean age of the patients was (66.7±9.2) years old and median PSA level was 28.50 (ranging 2.43 - 1481.11) ng/ml. Within these 249 patients, 84 (33.7%) were T 1-2, 98 (39.3%) were T 3-4, while 67 (26.9%) were unclear in T stage. Additionally, 51 patients (20.5%) were classified into International Society of Urological Pathology(ISUP) grade group 1-3 group and 198 patients (79.5%) were in ISUP 4-5 group. Focusing on 16 genetic susceptibility genes for prostate cancer, we interpret the germline genetic testing data in accordance with the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guideline, clarify the germline pathogenic mutation rate and elucidate the clinicopathological characteristics of germline pathogenic mutation carriers. Results:Among Chinese high-to very-high-risk non-metastatic prostate cancer patients, 7.2% (18/249) had germline pathogenic mutations. Patients with mutations had a significantly higher proportion of first-degree relatives with a history of malignancy than those without mutations (50% vs. 13%, P<0.001), but there was no difference in age of onset [(68.2±9.3)years vs. (66.6±9.2) years], PSA level (median: 40.68 ng/ml vs. 28.00 ng/ml), T stage [T 3-4: 38.9%(7/18)vs. 39.4%(91/231)] and ISUP grade [group 4-5: 88.9%(16/18) vs. 78.8%(182/231)]. Germline pathogenic mutations were observed in BRCA2 (7 patients, 38.9%), MSH2 (3 patients, 16.7%), PALB2 (2 patients, 11.1%), ATM (2 patients, 11.1%), RAD51C (1 patient, 5.6%), PMS2 (1 patient, 5.6%), MSH6 (1 patient, 5.6%) and HOXB13 (1 patient, 5.6%). By comparing with normal controls of East-Asian population, germline pathogenic mutations in BRCA2 ( OR=11.1, 95% CI 4.8-25.6, P<0.001) and MSH2 ( OR= 43.5, 95% CI 8.5-200.0, P<0.001) can significantly increase the risk of developing high- to very-high-risk prostate cancer in Chinese males. Conclusions:This study identified a germline pathogenic mutation rate of 7.2% in 249 Chinese patients with high- or very-high-risk non-metastatic prostate cancer. Carrying germline BRCA2 or MSH2 pathogenic mutations can significantly increase the risk of high- or very-high-risk prostate cancer in Chinese men.

6.
Chinese Journal of Urology ; (12): 484-489, 2022.
Article in Chinese | WPRIM | ID: wpr-957414

ABSTRACT

Objective:To explore clinical value of prostate target biopsy guided by multiparametric magnetic resonance imaging (mpMRI) and 68Ga-labeled prostate specific membrane antigen ligand imaging positron emission tomography/X-ray computed tomography ( 68Ga-PSMA PET/CT) image fusion. Methods:The data of 50 patients admitted to Fudan University Shanghai Cancer Center from January 2021 to February 2022 who underwent mpMRI and 68Ga-PSMA PET/CT to guide prostate biopsy were retrospectively analyzed. The median age was 70 (63-79) years, the median serum tPSA value was 8.1 (6.8-83.0) ng/ml, and the prostate volume was 45.5 (30-80) ml. 36 cases were positive by mpMRI, including PI-RADS score 3 in 5 cases, 4 score in 19 cases, 5 score in 12 cases. 32 cases were positive by 68Ga-PSMA PET/CT examination, of which 30 cases were double positive and the fusion of both imaging techniques was positive, referred to as PET/CT-MRI. The patient's mpMRI and 68Ga-PSMA PET/CT images were imported into the MIM fusion software, and the outline of the prostate and the target area were outlined respectively. When PET/CT and MRI double positive cases were biopsied, the two images were alternately fused, calibrated and locked with the real-time prostate ultrasound interface(PET/CT-MRI). Single-positive cases were guided by positive images to complete targeted biopsy, and 12-needle systematic biopsies were completed after targeted biopsy and double-negative cases. The advantages of targeted biopsy and systematic biopsy was evaluated, and the diagnostic performance (sensitivity, specificity, positive predictive value, and negative predictive value) was analyzed. Results:Among the 50 biopsy patients in this group, 31 (62%) had prostate cancer, of which 22 (44%) were CsPCa. There was no significant difference in the detection rate of prostate cancer between targeted biopsy and systematic biopsy [78.9% (30/38) and 62.0% (31/50), P=0.088], and there was no significant difference in the detection rate of CsPCa [57.9% (22/38) and 40.0% (20/50), P=0.096]. The positive rate of the biopsy needles number was significantly different [86.3% (69/80) and 19.0% (114/ 600), P<0.001]. The detection rates of prostate cancer in mpMRI positive, PET/CT positive and PET/CT-MRI positive cases were 83.3% (30/36), 90.6% (29/32) and 96.6% (29/30) respectively, the detection rates of CsPCa were 61.1% (22/36), 68.8% (22/32) and 73.3% (22/30) respectively.The sensitivity, specificity, positive predictive value and negative predictive value of mpMRI in the diagnosis of prostate cancer were 96.8%(30/31), 68.4%(13/19), 83.3%(30/36)and 92.9%(13/14), respectively.Those values in 68Ga-PSMA PET/CT were 93.5%(29/31), 84.2%(16/19), 90.6%(29/32)and 88.9%(16/18), respectively.Those values in PET/CT-MRI were 93.8%(29/31), 94.7%(18/19), 96.7%(29/30)and 90.0%(18/20), respectively. The above four indicators of mpMRI diagnosis of CsPCa were 100.0%(22/22), 50.0%(14/28), 61.1%(22/36)and 100.0%(14/14), respectively.Those indicators in 68Ga-PSMA PET/CT were 100.0%(22/22), 64.3%(18/28), 68.8%(22/32)and 100.0%(18/18), respectively.Those indicators in PET/CT-MRI was 100.0%(22/22), 71.4%(20/28), 73.2%(22/30)and 100.0%(20/20), respectively. The detection efficiency of PET/CT-MRI was better than that of mpMRI (Kappa value was 0.737, P=0.031). Conclusions:PET/CT-MRI image fusion-guided targeted prostate biopsy can effectively improve the detection efficiency of prostate cancer and clinically significant prostate cancer, and increase the positive rate.

7.
Chinese Journal of Urology ; (12): 397-400, 2021.
Article in Chinese | WPRIM | ID: wpr-885033

ABSTRACT

DNA damage repair gene mutations are prevalent in advanced prostate cancer. Among these, mutations in homologous recombination repair genes could impair the ability of cell to restore the DNA double-strand break, which can be exploited by Poly-ADP-ribose polymerase (PARP) inhibitors through synthetic lethality and result in cell death. The phase Ⅲ study " PROfound" showed that the PAPR inhibitor Olaparib could significantly improve the survival of patients with homologous recombination repair gene mutations compared with novel hormone agents, starting the era of targeted, precise and individualized treatment based on genetic profile detection for prostate cancer treatment.

8.
Chinese Journal of Urology ; (12): 54-58, 2021.
Article in Chinese | WPRIM | ID: wpr-911176

ABSTRACT

Retrospectively analyze the clinicopathological data of a patient with metastatic hormone sensitive prostate cancer, and review relevant literature. The patient was male, 68 years old. Complaints of dysuria and urgency for half a year. Blood PSA>100 ng/ml, magnetic resonance showed that the prostate was occupying space, the boundary with the seminal vesicle gland was not clear, and the pelvic cavity had multiple bone lesions. Bone scan revealed multiple bone metastases. The prostate biopsy showed adenocarcinoma, Gleason score 5+ 5. The clinical stage was T 3N 0M 1b.A palliative transurethral resection of the prostate was performed due to urination obstruction, and endocrine therapy with medical castration combined with abiraterone and prednisone. PSA was continuously controlled at <0.006 ng/ml. After half a year of treatment, the prostate-specific membrane antigen single-photon emission computerized tomography and magnetic resonance examination revealed sternal and parasternal soft tissue lesions. Local radiotherapy and continuous endocrine therapy were given. The disease was under long-term control.There are various treatment options for metastatic hormone sensitive prostate cancer. Medical castration treatment combined with abiraterone and prednisone can effectively control the disease with mild adverse reactions. Palliative transurethral resection of the prostate can improve the symptoms of urinary obstruction and may also improve the prognosis of patients.

9.
Chinese Journal of Urology ; (12): 747-751, 2021.
Article in Chinese | WPRIM | ID: wpr-911108

ABSTRACT

Objective:To investigate the current perceptions, treatment patterns and unmet needs of androgen deprivation therapy (ADT) on treating prostate cancer (PCa) by gonadotropin-releasing hormone agonist (GnRH-a) in Chinese urologists.Methods:The survey was conducted between July 2020 and August 2020. Questionnaires were designed to investigate the urologists employed by 163 grade A tertiary hospitals from 7 districts (North, Northeast, East, South, Central, Southwest, Northwest) across China. The inclusion criteria were urologists who had the title of attending physician or above, had experience of prescribing GnRH-a, and agreed to participate in the survey. An electronic self-administered structured questionnaire was used for data collection, with a target sample size of 300, covering treatment patterns, experience of GnRH-a prescription, and unmet needs of GnRH-a.Results:There were 13 886 questionnaires had been distributed, among which 410 questionnaires had met the inclusion criteria. After excluding 110 incomplete questionnaires, 300 valid questionnaires were included in the analysis. The average number of PCa patients administered castration treatment per urologist per month was 12±8. Monthly GnRH-a injection was more often used than quarterly GnRH-a injection[(62.0±24.7)% vs. (38.0±24.7)%]. The main follow-up frequency for patients receiving GnRH-a was once a month as reported by 49.3% (148/300) of urologists. GnRH-a injection frequency (31.3%, 94/300), prostate-specific antigen (PSA) testing frequency (27.7%, 83/300) and clinical effectiveness (26.0%, 78/300) were reported as top factors determining the follow-up frequency. Only 46.0% (138/300) urologists believed that over 70.0% of the patients were completely adherent to the prescribed treatment. When deciding which GnRH-a product to be prescribed, the top 4 factors considered by urologists were effectiveness (92.0%, 276/300), adverse events (85.7%, 257/300), economic burden (76.7%, 230/300), and frequency of injection (61.3%, 184/300). The urgency of improvement for each aspect of GnRH-a therapy was evaluated with a 5-point Likert scale (from 1 (not urgent) to 5 (extremely urgent)). The top 4 aspects needing further improvement were effectiveness (4.04±0.93), economic burden (3.93±0.84), adverse events (3.90±0.90), and frequency of injection (3.60±0.93). A 5-point Likert scale (from 1 (not influential) to 5 (extremely influential)) was also applied to evaluate factors influencing patients’ quality of life and the top 4 factors were pain (4.09±0.94), psychological stress (3.61±0.90), adverse events (3.46±0.89), and discomfort caused by frequent GnRH-a injection (3.34±0.91).Conclusions:Most urologists in China hoped that GnRH-a therapy could have reduced injection frequency, improved effectiveness, reduced economic burden and decreased adverse events in order to increase patient’s adherence and to improve the effectiveness of PCa treatment as well.

10.
Chinese Journal of Urology ; (12): 670-674, 2021.
Article in Chinese | WPRIM | ID: wpr-911093

ABSTRACT

Objective:To observe the clinical effect and safety of regional lymph node dissection in metastatic castration resistant prostate cancer(mCRPC).Methods:The clinical data of 22 patients with mCRPC who underwent regional lymph node dissection in our hospital from August 2015 to May 2021 were retrospectively analyzed. All patients had undergone radical prostatectomy and entered mCRPC, metastatic lymph nodes limited to pelvic or retroperitoneal without other metastasis were determined by PSMA-PET in 5 cases and PSMA-SPECT in 17 cases. The median time from radical surgery to mCRPC was 32 (4-96) months, and the median time from discovery of mCRPC to regional lymph node dissection was 4 (1-43) months. The median PSA before regional lymph node dissection was 4.44 (2.00-22.15) ng/ml. Image of local examination showed pelvic lymph node metastasis in 16 cases, retroperitoneal lymph node metastasis in 3 cases, pelvic together with retroperitoneal lymph node metastasis in 3 cases. Before regional lymph node dissection, 18 patients were treated with drug castration combined with first-generation antiandrogens, and 4 patients were treated with drug castration combined with abiraterone. The lymph node dissection range was determined according to the location of metastatic lymph nodes. Obturator lymph nodes and lymph node metastasis around external iliac and internal iliac vessels: the range of dissection includes fibrous adipose tissue around external iliac vein and internal iliac vein, and obturator lymph adipose tissue. Common iliac and pelvic floor lymph node metastasis: dissect lymphoid adipose tissue around common iliac vessels on the basis of the original dissection range as far as the aortic bifurcation. Retroperitoneal lymph node metastasis: remove all lymph node adipose tissue located between the bifurcation of renal artery and aorta. The PSA remission rate, PSA remission time, surgical complications and other relevant clinicopathological features were analyzed.Results:Among the 22 cases, 6 cases underwent unilateral pelvic lymph node dissection, 10 cases underwent bilateral pelvic lymph node dissection, 3 cases underwent retroperitoneal lymph node dissection, and 3 cases underwent pelvic and retroperitoneal lymph node dissection at the same time. 19 cases (86.3%) showed positive lymph nodes by pathology. An average of 9.8 (3-29) lymph nodes were dissected in each patient, with an average of 4.1 (0-12) positive lymph nodes. All 22 cases continued to use the previous anti-androgen therapy after lymph node dissection. 17 cases (77.3%) achieved PSA remission after operation, of which 9 cases developed PSA progression, and the median PSA progression time was 12 (2-36) months. Univariate analysis showed that PSA value during radical operation ( P=0.029), N stage during radical operation ( P=0.057), the number of positive lymph nodes during regional lymph node dissection ( P=0.069) and the location of lymph node metastasis during regional lymph node dissection ( P =0.005) were related to the progression time of PSA. Postoperative complications: lymphatic leakage in 7 cases; 5 cases of postoperative fever, of which 1 case was confirmed to have pelvic bacterial infection. One patient suffered from massive intra-operative bleeding due to the invasion of blood vessels by metastatic lymph nodes. After timely hemostasis during the operation, the patient returned to the ward and was discharged 6 days later. One case of intestinal obstruction, and 1 case of body surface wound infection. 6 cases of lymphatic leakage healed within 1 month after operation, and 1 case of lymphatic leakage healed within 3 months after operation. Conclusions:For mCRPC patients with lymph node metastasis which could be surgically removed, regional lymph node dissection may further delay the starting time of posterior drugs, and the complications are relatively controllable.

11.
Chinese Journal of Urology ; (12): 662-665, 2021.
Article in Chinese | WPRIM | ID: wpr-911091

ABSTRACT

Objective:To explore the clinical value of cryoablation technology in the treatment of patients with primary tumor recurrence after radical radiotherapy for prostate cancer.Methods:The clinical data of 21 patients with prostate cancer recurrence after radical radiotherapy in the Fudan University Affiliated Cancer Hospital from August 2017 to February 2021 was retrospectively analyzed. The average age was 73.1 (57.3-85.0) years old, and the Gleason score was 6 in 5 cases, 7 in 8 cases, and ≥8 in 8 cases. The clinical stage of the first diagnosis: 13 cases of cT 2 stage; 8 cases of cT 3 stage. The baseline PSA before radiotherapy was 35.3 (6.4-78.5) ng/ml, and the lowest PSA after radiotherapy was 1.8 ng/ml. After a median follow-up of 8 (3-12) months, all patients were detected with persistently elevated PSA. Pelvic MRI and PSMA SPECT showed that the primary prostate lesion had recurred. PSA before cryoablation was 4.1 (1.8-14.4) ng/ml. Comprehensive assessment of preoperative examination showed that the patient only had a recurrence of the primary tumor, and no lymph node or distant metastasis was seen. An argon-helium cryogenic surgical treatment system was used to place 1 to 3 cryo-needles for recurring lesions, and cryoablation was performed using two cold and hot cycles. Observation indicators include prognostic indicators such as PSA, recurrence and metastasis, and the occurrence of adverse reactions. Results:Complications after cryoablation include: 2 cases of urinary retention, 1 case of urinary tract infection, and 2 cases of urination with tissue shedding. The PSA of 11 cases decreased rapidly 2 to 3 months after operation, and dropped to the lowest median value of 0.4 (0.003 to 2.8) ng/ml. After cryoablation, the median follow-up was 18 (6-51) months. Imaging examinations in 1 case showed that the prostate still had limited diffusion or increased PSMA uptake, and 4 cases had PSA progression but no recurrence or metastasis. The median recurrence time for advanced patients was 13 (4-36) months. Larger prostate volume ( P<0.001) and higher blood PSA before ablation( P=0.021) were related to biochemical recurrence. Conclusions:Prostate cryoablation could delay the progression of the primary tumor after radical radiotherapy for prostate cancer. The incidence of complications such as urinary retention and urinary tract infection is not high, and it is generally safe and controllable.

12.
Chinese Journal of Urology ; (12): 641-643, 2021.
Article in Chinese | WPRIM | ID: wpr-911087

ABSTRACT

Prostate cancer is the most common solid malignant tumor among men in Western countries. While the incidence of prostate cancer is relatively low in Asia. In recent years, the incidence of prostate cancer in Asia is growing rapidly due to the development of social and economic level, popularization of people's health awareness and technological progress of health medicine in Asian countries. However, the uneven level of economic, social, human and medical aspects in Asian countries has also brought some difficulties and challenges to the standardized diagnosis and treatment of prostate cancer. Based on the Asian population, combined with the characteristics of Asian countries, this paper will explore the future directions of prostate cancer diagnosis and treatment in Asia from the development of prostate cancer diagnosis and treatment in China.

13.
Chinese Journal of Urology ; (12): 801-806, 2020.
Article in Chinese | WPRIM | ID: wpr-869774

ABSTRACT

The incidence of prostate cancer in China is growing rapidly in recent years. The leapfrog development of prostate cancer research in China during the last 40 years has been witnessed by "Chinese Journal of Urology" and divided into three major periods. First, the beginning phase during 1980 to 2000, when the Chinese urology community began to establish a professional and standardized prostate cancer treatment system. Second, the catching-up phase during 2001 to 2010, when Chinese urologists actively promoted prostate cancer diagnosis and treatment technology, and integrated with international advanced diagnosis and treatment concept. Third, the characteristics creating phase during 2011 to 2020, when prostate cancer research in China developed rapidly, and the voice of China is constantly being heard on the international stage. Based on the current prostate cancer research in China, it is also necessary to strengthen evidence-based medicine research, to focus on precision medicine research, to pay attention to real-world research, and to emphasize the importance of differences between China and the western countries. At last, Chinese prostate cancer patients will benefit more.

14.
Chinese Journal of Urology ; (12): 20-24, 2019.
Article in Chinese | WPRIM | ID: wpr-734565

ABSTRACT

Objective To investigate the short-term efficacy,safety and factors affecting the efficacy of BCG intravesical therapy in high risk non-muscle-invasive bladder cancer (NMIBC) patients.Methods A total of 161 high-risk non-muscle invasive bladder cancer (NMIBC) patients were reviewed in our hospital from March 2014 to December 2017.They were all treated with BCG instillation after transurethral resection of bladder tumor (TURBT).There were 121 males (75.2%) and 40 females (24.8%).Median age was 65 years old,including 17 cases (10.6%) <50 years old,23 cases (14.3%) within 50-59 years old,72 cases (44.7%) within 60-69 years old,49 cases ≥70 years old (30.4%).There were 112 patients (69.6%) with primary bladder cancer and 49 (30.4%) patients with recurrent bladder cancer.56 cases (34.8%) had single tumor and 105 cases (65.2%) had multiple tumors.The tumors size in 106 cases (65.8%) was less than 3 cm,and tumor size in 55 cases (34.2%) was more than 3 cm.43 patients (26.7%) suffered carcinoma in situ.10 patients (6.2%) suffered urothelial carcinoma with variant types.According to the American Joint Commission for Cancer (AJCC) version 7 TNM staging system,25 cases (15.5%) were classified into Ta stage,129 cases (80.1%) were classified into T1 stage,and 7 cases (4.3%) were classified into Tis stage.There were 8 cases (5%) with low-grade cancer and 153 cases (95%) with high-grade cancer.69 patients (42.9%) received chemo-instillation before.43 cases were directly perfused without re-TURBT and 118 cases were perfused after re-TURBT.They were all treated with BCG instillation after transurethral resection of bladder tumor (TURBT).The 120 mg BCG were dissolved into 50 ml saline for instillation and were kept for 2 hours.Induction scheme of six-weekly and three fortnightly instillations started two weeks after the initial TUR or re-TUR.Maintenance instillations were then be offered in a scheme of ten monthly instillations.During treatment,patients were offered cystoscopy and cytology every three months,while CT and chest radiographs were reviewed every 6-12 months.Recurrence status and adverse effects were recorded.Univariate and multivariate regression analyses were performed to predict risk factors for failure of BCG instillation in bladder cancer.Results A total of 161 patients were followed up.The median follow-up time was 13 months,ranging 7-22 months.The overall recurrence rate was 26.1% (42/161) and the 1-year recurrence-free survival rate was 79.0%.On univariate analysis,recurrence history,history of instillation chemotherapy application and history of re-staging transurethral resection influenced recurrence.Multivariate regression analysis showed recurrence status was an independent prognostic factor regarding recurrence-free survival.The incidence of adverse events in all 161 instillation patients was 40.4% (26/65).Grade 1,grade 2 and grade 3 adverse events accounted for 53.8% (35/65),40.0% (26/65) and 6.2% (4/65) respectively.6 cases (3.7%) reduced the dose of BGC and 1 case stop the instillation due to the intolerance of BCG.Conclusion Short-term efficiency and safety were confirmed in BCG-treated high-risk NMIBC patients.And recurrence status was an independent prognostic factor for recurrence-free survival.

15.
Chinese Journal of Urology ; (12): 661-667, 2019.
Article in Chinese | WPRIM | ID: wpr-797757

ABSTRACT

Objective@#To explore the predictive value of circulating tumor cells (CTCs) characterization for time to castration resistance of newly diagnosed high volume metastatic castration sensitive prostate cancer (mCSPC) patients.@*Methods@#Newly diagnosed high volume mCSPC patients were prospectively enrolled in this study from September 2015 to February 2017. The inclusion criteria include that the patients' age should be between 18 to 85 years old. The Prostate cancer should be diagnosed by biopsy or cytopathology. No endocrinological therapy, radiative therapy or chemotherapy was used before the study. High-volume metastatic lesion was confirmed by imaging. Those patients who accepted previous endocrinological therapy, radiative therapy or chemotherapy were excluded in this study. Those patients combined with concomitant tumor were also excluded. The health males were enrolled in the control group. All patients received androgen deprivation therapy (ADT) with goserelin plus bicalutamide (goserelin 3.6 mg subcutaneous injection, once a month plus bicalutamide 50mg orally, once a day). CanPatrol system was used to count CTCs in peripheral blood of patients and characterize CTCs based on expressions of epithelial markers(EpCAM and CK8/18/19) and mesenchymal markers(vimentin and twist). Primary endpoint was time to castration resistance. Survival analysis was conducted using Kaplan-Meier method and log-rank test was used to assess the difference of survival between groups, and univariate and multivariate analyses of prognostic factors were conducted using the Cox proportional hazards model.@*Results@#A total of 108 newly diagnosed high volume mCSPC patients were enrolled in this study. The median age of enrolled patients was 68 years old (ranging 51-85 years old), and median PSA was 196.2 ng/ml(ranging 5.8-5 011.9 ng/ml). The median level of hemoglobin was 32 g/L(ranging 9-172 g/L). The median level of LDH was 179 U/L(ranging 49-630 U/L). The ECOG scores was 0-1 score in 94 cases(87.0%), 2 scores in 14 cases (13.0%). The Gleason scores was 6-7 in 20 cases (18.5%) and more than 8 in 88 cases (81.5%). All patients had bone metastatic lesions, among which 41 (38.0%) patients had more than 10 metastatic lesions and 6 (5.6%) patients with visceral metastasis, 30(27.8%) patients with limb bone metastasis. The median CTCs count was four, and ranging 0-35. Mesenchymal CTCs positive and negative (negative included CTCs negative, epithelial CTCs positive and biophenotypic CTCs positive) patients were 58(53.7%) and 50, respectively. There was no correlation between CTCs characterization with age, baseline PSA, Gleason score, ALP and other clinical parameters (P>0.05). In control group, the mean age was 26 years old (ranging 20-31 years old). No CTCs were detected among those people. After a median follow-up of 24 months (ranging 18-32 months), 90 patients (83.3%) progressed to castration resistant prostate cancer (CRPC). The median time to CRPC for patients of mesenchymal CTCs positive and negative was (10.5±1.4) and (14.0±3.4) months, respectively(P<0.001). Univariate analysis revealed CTCs characterization(HR=1.647, P=0.003), the number of metastatic lesions (HR=1.624, P=0.025)and limb bone metastasis(HR=1.706, P=0.019) were prognostic factors of time to CRPC; further multivariate analysis showed that only baseline mesenchymal CTCs positive (HR=1.562, P=0.008) was independent prognostic factors of unfavorable time to CRPC.@*Conclusions@#CTCs characterization can predict time to CRPC of newly diagnosed high volume mCSPC patients receiving ADT, and patients of baseline mesenchymal CTCs positive are more likely to progress to CRPC.

16.
Chinese Journal of Surgery ; (12): 418-421, 2019.
Article in Chinese | WPRIM | ID: wpr-810655

ABSTRACT

Objective@#To investigate the short-term efficacy and adverse events of chemotherapy combined with androgen-deprivation therapy in high-volume metastatic hormone sensitive prostate cancer.@*Methods@#From March 2015 to August 2017, 55 patients with high-volume metastatic hormone sensitive prostate cancer were enrolled at Department of Urology, Fudan University Shanghai Cancer Center receiving chemotherapy combined with androgen-deprivation therapy. The age was 65(8) years (M(QR)) (range: 46 to 79 years). Patients were enrolled in the study for continuous androgen-deprivation therapy (medical or surgical castration), combined with docetaxel 75 mg/m2 intravenous injection on the first day, repeated every 21 days (6 cycles). Endpoints included overall survival, progression-free survival of prostate cancer, prostate specific antigen (PSA) response rate, and adverse events.@*Results@#The follow-up time was 21.2(11.7) months. The PSA value before chemotherapy was 144.9(415.3) μg/L. The days in patients undergoing androgen deprivation therapy before chemotherapy was 14(23) days. Four patients (7.3%) presented 0 in Eastern Cooperative Oncology Group scoring system and 51 patients(92.7%) presented 1. Thirty-nine patients (70.9%) completed more than 6 cycles of combined chemotherapy, 17 patients (30.9%) showed PSA<0.2 μg/L at 6 months after treatment, and 14 patients (25.5%) showed PSA<0.2 μg/L at 12 months after treatment. Twenty-eight patients (50.9%) had grade 3 to 4 neutropenia and 1 patient (1.8%) developed infectious neutropenia and died. Nausea and vomit occurred in 16 patients (29.1%). Twelve patients (21.8%) underwent dose adjustment due to adverse events in blood system.@*Conclusions@#The short-term effect was confirmed in high-volume metastatic hormone sensitive prostate cancer using chemotherapy combined androgen-deprivation therapy, and the long-term effect remains to be seen. Myelosuppression during chemotherapy requires close attention, and taking timely examination is recommended.

17.
Chinese Journal of Surgery ; (12): 401-403, 2019.
Article in Chinese | WPRIM | ID: wpr-810651

ABSTRACT

In recent years, morbidity and mortality of prostate cancer in China have increased rapidly, and it has become a common malignant tumor among the top 5 male tumors in some areas. Multidisciplinary comprehensive treatment is the key to improve the survival rate and quality of life of prostate cancer. However, the drugs used to construct multidisciplinary comprehensive treatment were based on anatomy, treatment stage and clinical trials, which lacked individualized treatment for complex tumor scenarios. With the rapid development of precision medicine, molecular imaging, molecular typing and pharmacogenomics will be added to these three elements, which will help to improve the individualized level of multidisciplinary comprehensive treatment. This kind of precise multidisciplinary comprehensive treatment urgently needs the vigorous promotion of ideas, researchers and researches.

18.
Chinese Journal of Urology ; (12): 661-667, 2019.
Article in Chinese | WPRIM | ID: wpr-791668

ABSTRACT

Objective To explore the predictive value of circulating tumor cells (CTCs) characterization for time to castration resistance of newly diagnosed high volume metastatic castration sensitive prostate cancer (mCSPC) patients.Methods Newly diagnosed high volume mCSPC patients were prospectively enrolled in this study from September 2015 to February 2017.The inclusion criteria include that the patients'age should be between 18 to 85 years old.The Prostate cancer should be diagnosed by biopsy or cytopathology.No endocrinological therapy,radiative therapy or chemotherapy was used before the study.High-volume metastatic lesion was confirmed by imaging.Those patients who accepted previous endocrinological therapy,radiative therapy or chemotherapy were excluded in this study.Those patients combined with concomitant tumor were also excluded.The health males were enrolled in the control group.All patients received androgen deprivation therapy (ADT) with goserelin plus bicalutamide (goserelin 3.6 mg subcutaneous injection,once a month plus bicalutamide 50mg orally,once a day).CanPatrol system was used to count CTCs in peripheral blood of patients and characterize CTCs based on expressions of epithelial markers(EpCAM and CK8/18/19) and mesenchymal markers (vimentin and twist).Primary endpoint was time to castration resistance.Survival analysis was conducted using Kaplan-Meier method and log-rank test was used to assess the difference of survival between groups,and univariate and multivariate analyses of prognostic factors were conducted using the Cox proportional hazards model.Results A total of 108 newly diagnosed high volume mCSPC patients were enrolled in this study.The median age of enrolled patients was 68 years old (ranging 51-85 years old),and median PSA was 196.2 ng/ml (ranging 5.8-5 011.9 ng/ml) . The median level of hemoglobin was 32 g/L(ranging 9-172 g/L).The median level of LDH was 179 U/L(ranging 49-630 U/L).The ECOG scores was 0-1 score in 94 cases(87.0%),2 scores in 14 cases (13.0%).The Gleason scores was 6-7 in 20 cases (18.5%) and more than 8 in 88 cases (81.5%).All patients had bone metastatic lesions,among which 41 (38.0%) patients had more than 10 metastatic lesions and 6 (5.6%) patients with visceral metastasis,30 (27.8%) patients with limb bone metastasis.The median CTCs count was four,and ranging 0-35.Mesenchymal CTCs positive and negative (negative included CTCs negative,epithelial CTCs positive and biophenotypic CTCs positive) patients were 58 (53.7%) and 50,respectively.There was no correlation between CTCs characterization with age,baseline PSA,Gleason score,ALP and other clinical parameters (P > 0.05).In control group,the mean age was 26 years old (ranging 20-31 years old).No CTCs were detected among those people.After a median follow-up of 24 months (ranging 18-32 months),90 patients (83.3%) progressed to castration resistant prostate cancer (CRPC).The median time to CRPC for patients of mesenchymal CTCs positive and negative was (10.5 ± 1.4) and (14.0 ± 3.4) months,respectively (P < 0.001).Univariate analysis revealed CTCs characterization(HR =1.647,P =0.003),the number of metastatic lesions (HR =1.624,P =0.025) and limb bone metastasis(HR =1.706,P =0.019) were prognostic factors of time to CRPC;further multivariate analysis showed that only baseline mesenchymal CTCs positive (HR =1.562,P =0.008) was independent prognostic factors of unfavorable time to CRPC.Conclusions CTCs characterization can predict time to CRPC of newly diagnosed high volume mCSPC patients receiving ADT,and patients of baseline mesenchymal CTCs positive are more likely to progress to CRPC.

19.
China Oncology ; (12): 81-87, 2018.
Article in Chinese | WPRIM | ID: wpr-701056

ABSTRACT

Bladder cancer is one of the common genitourinary malignancies. Since the discovery of intravesical Bacillus Calmette-Guerin (BCG) in the 1970s for non-muscle invasive bladder cancer, there have not been any major breakthrough drugs especially for locally advanced and metastatic bladder cancer. Recently, the immunotherapy for bladder cancer has made great breakthrough. Immune-checkpoint inhibitors targeting the programmed death 1 (PD-1), programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) pathways have shown significant long-term responses and tolerable safety profiles for locally advanced and metastatic bladder cancer. Inhibitors targeting PD-1, PD-L1 and CTLA-4 are mainly used to restore T cell activity by blocking negative regulation signal, and to enhance the anti-tumor activities of T cells. Other immunotherapies including chimeric antigen receptor T-cell (CAR-T) therapy also have great prospects. In this review, the effect of immunotherapeutic agents and the mechanisms in the treatment of bladder cancer are summarized.

20.
China Oncology ; (12): 496-500, 2017.
Article in Chinese | WPRIM | ID: wpr-616283

ABSTRACT

Background and purpose:Liquid biopsy is a kind of blood, urine and other non-solid biologi-cal tissue sampling analysis, mainly for malignant tumor diagnosis, monitoring and predicting its prognosis. In this research, we optimized the extraction of miRNA in urine, established a standardized means of liquid biopsy, screened and verified the miRNA markers in patients with bladder cancer.Methods:From Jan. 2014 to Sept. 2015, we used miRNA microarray in six patients with bladder cancer and six healthy controls. Samples of 78 cases of bladder cancer and 23 healthy controls were tested by real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR) to verify the relationship between miRNA markers in liquid biopsy and clinical pathological parameters. The diagnostic value of miRNA markers was also analyzed and compared.Results:We screened 10 miRNAs differential expression in urine. Combined with previous literature, we selected 20 miRNAs to verify their expression levels in bladder cancers and healthy controls. miR-509-5p/miR-124 ratio in the urine was found higher in patients with bladder cancer than in healthy controls (P<0.0001). With the rise of miR-509-5p/miR-124 ratio in urine, tumor stage and grade were also increased (P=0.003). When the cutoff was set at 0.41, the diagnostic sensitivity and specificity of miR-509-5p/miR-124 ratio were 73.1% and 82.6%, respectively. The AUC of miR-509-5p/miR-124 ratio to detect bladder cancer was 0.864, higher than that of urinary exfoliated cells (P=0.0002).Conclusion:We optimized the extraction of miRNAs in urine,established a standardized liquid biopsy of miRNA markers. The miR-509-5p/miR-124 ratio could be an ideal diagnos-tic marker for bladder cancer.

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