636 Background: Upper Tract Urothelial Carcinoma (UTUC) presents a challenging prognosis even after Radical Nephroureterectomy (RNU), and postoperative renal insufficiency further limits the options for adjuvant therapy. The efficacy of neoadjuvant chemotherapy for UTUC remains uncertain as past studies have not shown satisfactory results and have mostly been retrospective. There is an urgent need for a more promising regimen. This phase II study aims to investigate the efficacy and safety of a combination of chemotherapy (Gemcitabine/Cisplatin) and PD-1 inhibitor (Toripalimab) as neoadjuvant treatment (NT) in UTUC patients. Methods: We planned to enroll 34 UTUC patients with either cT1N0M0 (high grade) or cT2-3N0M0, confirmed by ureterorenoscopy biopsy and imaging. The treatment regimen included three or four cycles of NT (Gemcitabine, 800mg/m 2 , days 1 and 8/Cisplatin, 60mg/m 2 , day 1/Toripalimab, 240mg, day 1 of a 21-day cycle), followed by RNU and pelvic lymphadenectomy. The primary outcome was the pathological complete response (pCR) rate, with secondary outcomes including significant downstaging (≤pT1) rate, disease control rate (DCR), and safety. Results: To date, 17 patients have been accrued since August 1st, 2020, and recruitment is ongoing. Fifteen patients have completed treatments and were preliminarily analyzed, with two patients still undergoing treatment. The median age was 66.0 years, with 53.3% being male. The majority of patients had unifocal tumors, with a median maximum diameter of 2.8cm (0.4-5.8). All patients experienced obstructed hydronephrosis. Clinical T staging was confirmed by multi-parameter MRI, indicating two T2 and thirteen T3 patients. Ureterorenoscopy biopsy revealed 13 high-grade and two low-grade urothelial carcinoma patients. All patients were classified as high-risk UTUC. Twelve patients completed 4 cycles, and three underwent 3 cycles. The median interval time from initiation of NT to RNU and from the end of NT to RNU was 18.3 (11.4-22.7) weeks and 6.3 (0.1-11.6) weeks respectively. The pCR rate was 20.0% (3/15), the ≤pT1 rate was 53.3% (8/15), and the DCR was 100%. No grade 4-5 chemotherapy-related adverse events were recorded, but 26.7% (4/15) experienced grade 2 myelosuppression, 20% (3/15) grade 3, and 6.7% (1/15) grade 4. Two patients experienced immune-related adverse events after 4 cycles, including hypothyroidism (grade 2) and adrenal insufficiency (grade 2). No surgery-related complications or readmissions within one month were reported. With a median follow-up of 25.6 months, all patients remained alive and tumor-free. Conclusions: Preliminary analyses suggest that the combination of chemotherapy and a PD-1 inhibitor as NT exhibits promising pCR rate for UTUC. The treatment was manageable in terms of safety, with immune-related adverse events potentially leading to prolonged treatment periods. Clinical trial information: NCT04099589 .

Abstract Background Non-invasive, especially the urine-based diagnosis of prostate cancer (PCa) remains challenging. Although prostate cancer antigen (PSA) is widely used in prostate cancer screening, the false positives may result in unnecessary invasive procedures. PSA elevated patients are triaged to further evaluation of free/total PSA ratio (f/t PSA), to find out potential clinically significant PCa before undergoing invasive procedures. Genomic instability, especially chromosomal copy number variations (CNVs) were proved much more tumor specific. Here we performed a prospective study to evaluate the diagnostic value of CNV via urine-exfoliated cell DNA analysis in PCa. Methods We enrolled 28 PSA elevated patients (≥ 4 ng/ml), including 16 PCa, 9 benign prostate hypertrophy (BPH) and 3 prostatic intraepithelial neoplasia (PIN). Fresh initial portion urine was collected after hospital admission. Urine exfoliated cell DNA was analyzed by low coverage Whole Genome Sequencing, followed by CNV genotyping by the prostate cancer chromosomal aneuploidy detector (ProCAD). CNVs were quantified in absolute z-score (|Z|). Serum free/total PSA ratio (f/t PSA) was reported altogether. Results In patients with PCa, the most frequent CNV events were chr3q gain (n = 2), chr8q gain (n = 2), chr2q loss (n = 4), and chr18q loss (n = 3). CNVs were found in 81.2% (95% Confidence Interval (CI) 53.7–95.0%) PCa. No CNV was identified in BPH patients. A diagnosis model was established by incorporating all CNVs. At the optimal cutoff of |Z|≥ 2.50, the model reached an AUC of 0.91 (95% CI 0.83–0.99), a sensitivity of 81.2% and a specificity of 100%. The CNV approach significantly outperformed f/t PSA (AUC = 0.62, P = 0.012). Further analyses showed that the CNV positive rate was significantly correlated with tumor grade. CNVs were found in 90.9% (95% CI 57.1–99.5%) high grade tumors and 60.0% (95% CI 17.0–92.7%) low grade tumors. No statistical significance was found for patient age, BMI, disease history and family history. Conclusions Urine exfoliated cells harbor enriched CNV features in PCa patients. Urine detection of CNV might be a biomarker for PCa diagnosis, especially in terms of the clinically significant high-grade tumors.

Abstract Background This study aimed to evaluate the feasibility and safety of online adapt-to-shape (ATS) workflow for prostate cancer patients on 1.5-T MR linac in China. Methods This prospective phase II study enrolled patients with localized or oligometastatic prostate cancer. Ultra-hypofractionated radiotherapy (UHF-RT) with dose of 36.25-40 Gy in five fractions was delivered every other day. After each fraction, feasibility and tolerability of the treatment were assessed. The primary endpoints were acute grade 2 or above genitourinary (GU) and gastrointestinal (GI) toxicities after up to 12 weeks follow-up.Results From March 2021 to November 2021, 26 patients were enrolled (23 with localized prostate cancer, 3 with oligometastatic prostate cancer). For all fractions, the online ATS plans met the dose criteria for both the target volume and normal tissues. The median on-couch time was 55 (34-95) minutes and 39 (24-50) minutes with T2WI 6-minute sequence and 2-minute sequence scans, respectively. For 98.4% fractions, treatment was well tolerated. Twenty-four patients completed treatment and were followed-up for at least 2 weeks. Grade 2 or above GU and GI toxicities occurred in 33.3% and 8.3% patients, respectively; two patients had RTOG grade 3 GU toxicity (hourly nocturia). IPSS remained unchanged during UHF-RT, increased from week 2 (mean, 9.1) to week 4 (mean, 12.4), and then gradually decreased at week 6. Patient-reported urinary and bowel scores were consistent with IPSS.Conclusions UHF-RT with ATS workflow is well tolerated by patients with localized and oligometastatic prostate cancer, with only moderate GU and mild GI toxicities. Trial Registration: NCT05183074, ChiCTR2000033382

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.

Objective To improve the accuracy of preoperative diagnosis of renal vein tumor thrombus in renal cell carcinoma (RCC),the clinical characteristics of RCC with misdiagnosis of renal vein tumor thrombus (RVTT) were analyzed.Methods Clinical data of 128 patients with RCC accompanied with RVTT from January 2000 to September 2015 were studied retrospectively.According to whether RVTT failed to be detected preoperatively,all patients were divided into 39 cases of misdiagnosis group and 89 cases of no misdiagnosis group.Forty cases of RCC with pathologically confirmed no RVTT were selected as no tumor thrombus group from January 2015 to June 2015.Misdiagnosis group included 29 males and 10 females,with age of (61.4 ± 11.1) years old,body mass index of (26.74 ±3.12) kg/m2,KPS ＜80 in 2 cases,paraneoplastic syndrome and Mayo grade 0 in 1 case.No misdiagnosis group consisted of 74 males and 15 females,with age of (60.2 ± 9.7) years old,body mass index of (25.12 ± 1.93) kg/m2,KPS ＜ 80 in 5 cases,paraneoplastic syndrome and Mayo grade 0 in 7 cases.No tumor thrombus group comprised of 31 males and 9 females,with age of (59.5 ± 10.7) years old,body mass index of (24.48 ± 2.56) kg/m2,KPS ＜ 80 in 3 cases,and paraneoplastic syndrome in 3 cases.There was no significant difference in general clinical data between misdiagnosis group and no misdiagnosis group,and misdiagnosis group and no tumor thrombus group (P ＞ 0.05).The tumor location,tumor diameter and imaging data were compared between misdiagnosis group and no misdiagnosis group,and misdiagnosis group and no tumor thrombus group.Results There was no significant difference in term of tumor locating in the middle pole [56.4％ (22/39) vs.38.2％ (34/89)],tumor with collateral vessels [33.3％ (13/39) vs.31.5％ (28/89)] and renal vein contrast agents filling defect [42.9％ (9/21) vs.61.8％ (21/34)] between misdiagnosis group and no misdiagnosis group (P ＞ 0.05).The proportion of renal tumor locating in the middle pole,tumor with collateral vessels and renal vein contrast agents filling defect in misdiagnosis group was significantly higher than that of no tumor thrombus group [30.0％ (12/40),P =0.018;10.0％ (4/40),P =0.012;16.7％ (4/24),P =0.002].Conclusions RVTT is vulnerable of misdianosis in RCC.It should be alert to the possibility of complicating tumor thrombus in the presence of renal tumor locating in the middle pole,renal tumor with collateral vessels and renal vein contrast agents filling defect.The clinical understanding of these features should be improved.

Background Previous related studies have mainly focused on renal cell carcinoma (RCC) with venous tumor thrombus, specifically inferior vena cava tumor thrombus with renal vein tumor thrombus (RVTT). However, only a few studies have focused on postoperative long-term survival of RCC patients exclusively with RVTT. Our aim was to investigate the independent prognostic factors for locally advanced RCC with RVTT in China. Methods Patients with locally advanced RCC with RVTT were enrolled for the study from January 2000 to December 2015. All patients underwent radical nephrectomy. Survival analysis was estimated using Kaplan-Meier. Univariable and multivariable survival analyses were performed using COX. Patients were divided into high-risk, middle-risk, and low-risk groups based on independent prognostic factors and then analyzed for survival. Results One hundred twenty-eight consecutive patients (103 men & 25 women) were enrolled with a median age of 61 years. Thrombi were all graded 0 using the Mayo system, of which 23 were friable. None of the thrombi detached during surgery. 121 patients were successfully followed up, with a median follow-up period of 47 months. Median overall survival was 127 months (95%CI: 101–153). The 5-year and 10-year cancer-specific survival (CSS) rate was 67.9 and 57.0%. 59 patients had recurrence with median time of 40 months. Friable thrombus, paraneoplastic syndrome (PNS), modified Fuhrman grade 3/4 and perirenal fat invasion were independent prognostic factors ( p < 0.05). The 5-year CSS for the Low-risk group (no factors) was 100%, Middle-risk group (1–2 factors) was 68.6%, while the High-risk group (3–4 factors) was 0%. Conclusions After radical surgery, RCC patients with RVTT had a relatively fair prognosis except for patients with friable thrombus, PNS, higher modified Fuhrman grade and perirenal fat invasion.

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.

目的 探讨无远处转移肾癌伴肾静脉瘤栓患者行开腹根治性肾切除联合瘤栓取出术的预后影响因素. 方法 回顾性分析2000年1月～2014年9月我院113例术后病理证实为肾癌伴肾静脉瘤栓的临床资料,均为May0 0级瘤栓,采用Kaplan-Meier生存分析,Cox比例风险模型评价肾癌伴肾静脉瘤栓的预后. 结果 106例获得随访,随访率93.8％(106/113),中位随访时间61个月(12～186个月),36例死亡,中位生存127个月(5～186个月),5年肿瘤特异性生存率(cancer-specific survival,CSS)为61.3％,10年CSS为50.4％.Cox比例风险模型结果显示副瘤综合征(β=2.457,P=0.000)、Fuhrman分级(G3/4) (β =2.617,P=0.000)和肾周脂肪受累(β=1.369,P=0.002)是肾癌伴肾静脉瘤栓患者的独立预后因素,同时伴有3项危险因素的患者中位生存仅14个月. 结论 术前无远处转移的肾癌伴肾静脉瘤栓患者行开腹根治性肾切除联合瘤栓取出术后预后良好,伴有副瘤综合征,高Fuhrman分级和肾周脂肪受累的患者预后差.

Objective To study the clinical features and prognosis of renal cell carcinoma patients with peritoneal invasion but without lymphatic or systemic metastasis (T4N0M0).Methods We reviewed patients with pathological stage of T4N0M0 from Jan.1999 to Feb.2012.There were 16 patients (9 males,7 females) met the inclusion criteria.There were 6 tumors on the left while other l0 on right.The median patient age was 65 (ranged from 33-78) years,the medium size of the mass was 8.5 (ranged from 5.5-17.0)cm.Peritoneum was invaded in all these patients and all of them had radical nephrectomy and resection of a contiguous peritoneum successfully.Results These patients accounted for 0.21％ (16/2889) of all renal cell carcinoma cases or 21.62％ (16/74) of all T4NxMx cases during this period.All patients were followedup for 18-134 month.Metastases were found in 8 patients at a median 6.5 (ranged from 1-41) month after surgery.9 patients were survival with disease-free,1 patient were survival with disease progression,6 patients died after surgery.The 3 years and 5 years of cumulative survival rate were 79.32％ and 64.90％,respectively.Conclusions The incidence of renal cell carcinomas with peritoneal invaded only is rare.Patients accept a successfully radical nephrectomy and resection of a contiguous peritoneum will have a good prognosis.

OBJECTIVE:To assess serum levels of endogenous endostatin in patients with clear cell renal cell carcinoma (CCRCC) and to determine the relationship of these levels to tumor stage, grade. METHODS:From March 2004 to October 2008, preoperative serum were obtained from 138 consecutive patients with CCRCC (73 patients in T1, 39 patients in T2, 20 patients in T3, and 6 patients in T4) and 40 healthy controls. Serum levels of endostatin were measured by sandwich-ELISA. Associations between circulating endostatin levels and clinicopathologic factors and clinical outcome were determined. RESULTS:Endostatin levels did not differ significantly between the patients with CCRCC (93.1 microg/L) and healthy controls (78.9 microg/L, P > 0.05). Serum levels of endostatin were significantly higher in the T2-4 CCRCC patients (107.2 microg/L) than those of the T1 patients (80.4 microg/L, P < 0.01). No significant difference was found in the endostatin levels among the T2-4 patients, or between healthy controls and the T1 patients. The serum endostatin concentration was significantly higher in the metastasis group (118.4 microg/L) than in the no metastasis group (89.5 microg/L, P < 0.05), but there was no significant difference between patients with distant metastasis group (122.0 microg/L) and lymph nodes metastasis (110.0 microg/L, P > 0.05). Patients with G3-4 tumors had significantly higher endostatin levels (111.8 microg/L) than those of patients with G1 (80.4 microg/L) and G2 tumors (86.2 microg/L, P < 0.01), but endostatin levels did not differ significantly between the two groups (P > 0.05). CONCLUSION:Preoperative serum levels of endostatin elevated in patients with CCRCC and associated with higher stage and grade.

OBJECTIVE:To summarize the experience in diagnosis and treatment of urachal mass in adults.METHODS:The clinical data of 33 patients with urachal mass, 21 male and 12 females, aged 49 (30-75), were analyzed retrospectively.RESULTS:The urachal masses of 11 patients (33%, 11/33) were benign, including 5 cases of abscess, 3 of cyst, 2 of malacoplakia, and 1 of xanthogranuloma. The most common symptom of the benign urachal mass was abdominal mass (36%). Seven patients underwent computed tomography (CT) and no calcification was found. All 11 patients were treated successfully by mass excision. Twenty-two cases (67%) had urachal carcinomas, including 17 cases of adenocarcinoma, 4 of squamous carcinoma, and 1 of transitional cell carcinoma. The most common symptom was gross hematuria (68%) in the malignant urachal mass patients and CT showed calcification in 38% of them (5/13). The overall 5-year cancer-specific survival rate was 45.2%. Nine patients with localized cancer underwent extended partial cystectomy with a 5-year cancer-specific survival rate of 78.3%. The patients with metastatic urachal cancer underwent multimodal treatment with an objective response rate of 50% for chemotherapy and 25% for radiation therapy. The median survival time after metastasis of the 8 cases given multimodal treatment was 14.0 months, 7.5 months longer than that of the 4 cases untreated (6.5 months, P = 0.09).CONCLUSION:The majority of urachal mass in adults is malignant. CT helps in distinguishing the benignancy from malignancy of urachal mass. Surgical excision affords good course for benign urachal mass. Extended partial cystectomy provides a curative surgical treatment for localized urachal cancer. The prognosis of metastatic urachal cancer is poor. Active multimodal treatment may improve the survival of patients with metastatic disease.