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Objective:To investigate the long-term survival and safety in patients with muscle-invasive bladder cancer (MIBC) who experienced a noninvasive down-staging (≤pT 1)after transurethral resection of bladder tumor (TURBT) plus systemic chemotherapy and received bladder-sparing treatment. Methods:The records of patients with MIBC who underwent maximal TURBT plus systemic chemotherapy-guided bladder-sparing treatment were reviewed retrospectively from Dec 2013 to Dec 2020. Eventually, 22 patients who achieved noninvasive down-staging underwent conservative management. The total patient cohort contained 10 males and 12 females. A majority of patients had single lesion and stage T2 disease. The median age of the patients was 66 years and the median tumor size was 3.0 cm. All patients underwent maximal TURBT to resect all visible diseases and followed by 3-4 cycles platinum-based systemic chemotherapy. After achieving noninvasive down-staging, 14 patients received concurrent chemoradiotherapy, and the other 8 patients underwent surveillance. Overactive bladder symptom score (OABSS) was used to assess the bladder function after treatment.Results:Twelve patients achieved pT 0 and 10 patients were down-staged to cT a-T 1. At a median follow-up of 36.7 months, 90.9%(20/22) patients retained their bladder function successfully. Among the 14 patients who received concurrent chemoradiotherapy, 4 had grade 3 or 4 adverse events. Among the 8 patients who underwent surveillance, 3 had grade 3 or 4 adverse events after systemic chemotherapy.Nine patients experienced tumor recurrence in the bladder, and 2 patients died of bladder cancer. Seven (31.8%) patients experienced Ⅲ/Ⅳ grade complications. The 5-year recurrence-free survival (RFS) and overall survival (OS) in patients achieved pT0 were 66.7% and 100.0%, respectively. The 5-year RFS and OS in patients achieved cTa-T1 were 40% and 72%, respectively. The OABSS score of 20 patients who retained their bladder successfully was (1.00±1.03). Conclusions:MIBC patients who achieved noninvasive down-staging might be candidates for the bladder-sparing treatment with maximum TURBT followed by systemic chemotherapy.The patients who achieved pT 0 might have better prognosis with functional bladder.
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Purpose@#Reduced quality of life after cystectomy has made bladder preservation a popular research topic for muscle-invasive bladder cancer (MIBC). Previous research has indicated significant tumor downstaging after neoadjuvant chemotherapy (NAC). However, maximal transurethral resection of bladder tumor (TURBT) was performed before NAC to define the pathology, impacting the real evaluation of NAC. This research aimed to assess real NAC efficacy without interference from TURBT and apply combined modality therapies guided by NAC efficacy. @*Materials and Methods@#Patients with cT2-4aN0M0 MIBC were confirmed by cystoscopic biopsy and imaging. NAC efficacy was assessed by imaging, urine cytology, and cystoscopy with multidisciplinary team discussion. Definite responders (≤ T1) underwent TURBT plus concurrent chemoradiotherapy. Incomplete responders underwent radical cystectomy or partial cystectomy if feasible. The primary endpoint was the bladder preservation rate. @*Results@#Fifty-nine patients were enrolled, and the median age was 63 years. Patients with cT3-4 accounted for 75%. The median number of NAC cycles was three. Definite responders were 52.5%. The complete response (CR) was 10.2%, and 59.3% of patients received bladder-sparing treatments. With a median follow-up of 44.6 months, the 3-year overall survival (OS) was 72.8%. Three-year OS and relapse-free survival were 88.4% and 60.0% in the bladder-sparing group but only 74.3% and 37.5% in the cystectomy group. The evaluations of preserved bladder function were satisfactory. @*Conclusion@#After stratifying MIBC patients by NAC efficacy, definite responders achieved a satisfactory bladder-sparing rate, prognosis, and bladder function. The CR rate reflected the real NAC efficacy for MIBC. This therapy is worth verifying through multicenter research.
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Objective:To evaluate the value of 68Ga-labeled prostate-specific membrane antigen( 68Ga-PSMA PET/CT)in the diagnosis of prostate cancer(PCa) and determination of the strategy on neurovascular bundle(NVB)preservation and lymphadenectomy before surgery. Methods:We retrospectively analyzed the clinical data of 46 patients with newly diagnosed PCa who underwent 68Ga-PSMA PET/CT from June 2018 to October 2019. The median age was 66.50 (60.00, 69.25) years old and the median PSA was 15.97(8.58, 33.10)ng/ml. Forty-one patients were diagnosed PCa and 5 were diagnosed with benign prostatic hyperplasia or prostatitis by 68Ga-PSMA PET/CT, 6 were diagnosed with lymph nodes metastasis. Forty patients underwent mpMRI, 33 were diagnosed PCa, and 6 were diagnosed with lymph nodes metastasis. Seventeen patients underwent 11C-choline PET/CT, 12 were diagnosed PCa, and 4 were diagnosed with lymph nodes metastasis. Among the 41 patients which were diagnosed PCa by 68Ga-PSMA PET/CT, 26 were confirmed with PCa by needling biopsy, 12 did not undergo the needling biopsy and 3 had negative biopsy; 22 were in the high-risk group, and 19 were in the low- and medium-risk group. All 41 patients underwent radical prostatectomy. The strategy of NVB preservation was determined by the position of the PCa reported by 68Ga-PSMA PET/CT. If the tumor was close to the unilateral prostate capsule, the healthy part of the NVB would be preserved. And if the tumor was limited in the prostate gland, bilateral NVB would be preserved. The NVB was preserved in 16 cases(6 cases unilateral and 10 cases bilateral). In addition to routine lymph node dissection for patients in the high-risk group, lymph node dissection was also performed on patients with 68Ga-PSMA PET/CT that showed positive lymph nodes in the low- and medium-risk groups. The paired chi-square or Fisher exact test was used to compare the sensitivity and specificity of 68Ga-PSMA PET/CT, mpMRI, and 11C-choline PET/CT for lesion detection. Spearman analysis was used to examine the correlation between the SUV max, Gleason score, and the PSA value before treatment. Results:Forty-one patients undergoing radical resection were diagnosed PCa by postoperative pathology, and no cancer tissue was observed at the surgical margin; the median Gleason score was 8(7, 9); 20 cases (48.8%) had a pathological stage ≤pT 2c; 21 cases (51.2%)≥pT 3; 7 cases were N+ (11 positive lymph nodes). Seven cases (17.1%) had complications of Clavien-Dindo ≤ grade 2 within 30 days after surgery, and there was no complication above grade 3 after surgery. The median follow-up time of the 41 patients was 16(12, 20). The rate of urinary control was 46.3%, 95.1%, and 100% after 1 month, 6 months, and 12 months follow-up respectively. Among the five patients that did not undergo surgery, the PSA value of 4 decreased after antibiotic treatment, and biopsy was performed in 1 case without PSA decreasing, and no carcinoma was found. The sensitivity of 68Ga-PSMA PET/CT on the primary PCa was 100%(41/41), which was significantly better than that of 11C-choline(80%, 12/15, P=0.016)and mpMRI (83.7%, 31/37, P=0.009), while no statistical significance was observed between the specificity of 68Ga-PSMA PET/CT (5/5)and 11C-choline PET/CT(2/2, P=1.000), 68Ga-PSMA PET/CT and mpMRI(1/3, P=0.107). Of the 41 patients that were diagnosed with PCa, the sensitivity of 68Ga-PSMA PET/CT to lymph nodes metastases(71.4%, 5/7) had a significant difference with that of mpMRI(16.7, 1/6, P=0.016), but no statistical difference with 11C-choline (75%, 3/4, P=1.000). Analysis of the relationship between SUV max of 68Ga-PSMA PET/CT, Gleason score, and PSA value before treatment revealed that the SUV max of 68Ga-PSMA PET/CT in patients with Gleason score ≥8 and <8 score were 19.60(9.58, 24.38) and 8.55 (5.18, 12.88); SUV max of patients with PSA values ≥20 ng/ml and <20 ng/ml before treatment were 19.40 (13.00, 23.50) and 8.40 (5.35, 13.95), respectively, the differences were statistically significant (all P<0.05). Conclusions:68Ga-PSMA PET/CT had high sensitivity and specificity for the diagnosis of primary prostate cancer lesions, but the sensitivity for the diagnosis of lymph node metastasis was not enough to guide the preoperative decision of whether to remove the lymph node and the scope of the removal. However, the treatment strategy of whether to retain NVB could be formulated according to the tumor location displayed by 68Ga-PSMA PET/CT before surgery.
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Objective To investigate the dose of docetaxel appropriate for patients with metastatic castration-resistant prostate cancer and its affects to the prognosis.Methods A retrospective analysis was performed on the clinical data of 75 patients with metastatic castration-resistant prostate cancer admitted from March 2010 to July 2016 who received docetaxel combined with prednisone chemotherapy.The patients were divided into the low-dose group (n =43,docetaxel ＜ 65 mg/m2),the middle-dose group (n =21,docetaxel 65-70 mg/m2) and the high-dose group (n =11,docetaxel ＞ 70 mg/m2).The median age in the low-dose group,middle-dose group and high-dose group was 67 (53-80),66 (56-78) and 61 (47-76) years old,respectively.Among 75 patients with bone metastasis,2 patients had no evidence of bone metastasis in the low-dose group.The lymph node metastasis was found in 26,13 and 6 cases in each group,respectively.And visceral and other metastasis were founded in 11,4 and 2 cases,respectively.The Gleason score in the low-dose group was≤7 points in 15 cases,≥8 points in 22 cases and no score in 6 cases.The Gleason score inthe middle-dose group was ≤7 points in 4 cases,≥8 points in 13 cases and no score in 4 cases.The Gleason score in the high-dose group was ≤7 points in 3 cases,≥8 points in 5 cases and no score in 3 cases.The number of patients with pain in the low-dose group,middle-dose group and high-dose group was 36,12 and 9,respectively,there were no significant differences in the above indicators (P ＞ 0.05),except age,which showed relatively more aged patients in the low-dose group,(P =0.045).Kaplan-Meier method was used to compare the overall survival (OS),progression-free survival (PFS) and the incidence of ≥CTCAE-4 grade 3 adverse reactions between the two groups.The Cox regression model was adopted to analyzed the factors that might affect patient prognosis,including the effective time of first-line endocrine therapy,hemoglobin level,ECOG score,pain score,number of cycles of chemotherapy,age,dose of docetaxel and alkaline phosphatase (ALP).Kaplan-Meier method was used to analyze the effect of dose of docetaxel on the prognosis,and log-rank method was used to test the significance of the results.Results The median OS was respectively 24.1,18.5 and 23.5 months in the low-dose group,middle-dose group and high-dose group,respectively.The median PFS was 5.3 months in all three groups,which didn't show statistically significant differences.The incidence of grade 3/4 adverse reactions in the low-dose group,middle-dose group and high-dose group was 15 cases (34.9％),8 cases (38.1％) and 5 cases (45.5％) respectively.It showed an increasing trend,but no statistically significant difference.The single factors related to OS mainly include the effective time of first-line endocrine therapy,hemoglobin level,ECOG score,pain score,number of cycles of chemotherapy,there was no significant correlation with age,docetaxel dose,ALP and PSA value.Conclusions It is common to receive lower doses of docetaxel in clinical practice for patients with metastatic castration-resistant prostate cancer in China.The efficacy of low-dose docetaxel is similar to that of high doses (standard dosage).There was no significant correlation between the OS and the actual dose of docetaxel in the tolerable range.
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Objective To evaluate the efficacy and safety of the modified docetaxel plus prednisone scheme for the metastatic castration resistant prostate cancer patients who got poor tolerance to chemotherapy.Method The clinical data of 50 metastatic castration resistant prostate cancer who received docetaxel + prednisone chemotherapy from March 2010 to October 2015 were analyzed retrospectively.23 cases received the modified DP regimen (modified group),27 cases received the standard DP regimen (standard group).The median age of the modified group and the standard group were 69 years (47-80 years) and 63 years (52-77 years) (P =0.005).There were 19 and 24 cases with pain in modified group and standard group respectively;10 and 19 cases with lymph node metastasis respectively;3 and 4 cases of visceral metastasis respectively;all of the 50 patients were complicated with bone metastasis.For the pathological Gleason score,there were 7 cases scored ≤7 points,13 cases scored ≥ 8 points and 3 cases unscored in the modified group;7 cases scored ≤7 points,15 cases scored ≥8 points and 5 cases unscored in standard group.There was no significant difference of the pain,metastasis,and Gleason score between the two groups (P ＞ 0.05).Progression free survival (PFS),overall survival (OS)and adverse events were analyzed using Kaplan-Meier curves,and the differences were assessed using the log-rank test.Results In the modified group and standard group,the median follow-up times were 11.0 months and 14.0 months respectively,the median chemotherapy cycles were 4.5 cycles and 5.0 cycles respectively;OS were 18.0 months and 27.5 months respectively (P =0.746).The PFS of the two groups were 6.0 months and 5.2 months,respectively (P =0.822).The PSA response were 13 cases and 17 cases in the modified group and standard group respectively (P =0.615),and the pain response were 8 cases and 7 cases (P =0.927),grade 3 to 4 adverse events were 3 cases and 14 cases (P =0.003).The main adverse events were blood toxicity,neutrophils,gastrointestinal reaction,edema,fatigue and oral mucositis etc.Conclusions Compared with the standard DP scheme,the modified DP scheme had no significant difference in OS,PFS,pain response rate and PSA response rate,while the incidence of grade 3 to 4 adverse events was significantly reduced.Modified DP scheme may be a better choice for patients with metastatic castration resistant prostate cancer who get poor tolerance to chemotherapy.
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Objective To investigate the effect of SMAD3 knockout on the reproduction of male mice.Methods Adult wild type females were mated with knockout or wild type males;Testis were performed with HE and TUNEL staining;Cauda epididymal sperms were counted and analyzed with morphology and motility.Results Wild-type / knock-out pairs resulted in a pregnancy rate of 92% with an average litter size of 5.45? 0.78 and a live birth rate of(87?19)%.In the wild-type / wild-type pairs,100% females were pregnant,the litter size was 6.01? 1.03,and the live rate was(97?15)%,there was no significant difference between the two groups.Histological analysis showed a relatively normal spermatogenesis in knockout testis,and TUNEL analysis did not demonstrate more apoptotic cells in knock-out testis.The cauda epididymal sperm number was normal,and there was no obvious difference in the sperm motility and morphology in the knock-out males.Conclusion The function of SMAD3 can be compensated in male reproduction.