Oncological outcome of surgical treatment in 336 patients with renal cell carcinoma

Background and Objective: The most effective therapy against renal cell carcinoma (RCC) is surgical treatment; however, there have been few large-scale studies that focused on the oncological outcome of this disease in China. The aim of the current study was to report the clinicopathological results and cancer-specific survival (CSS) rate in RCC patients after surgical treatment in our center. Methods: We retrospectively analyzed the clinicopathological data of 336 RCC patients who underwent radical or partial nephrectomy between 1999 and 2006. Of the 336 patients, 226 were male and 110 were female; the median age was 51 years. Univariate and multivariate analyses were conducted to identify the independent prognostic predictors for this cohort of RCC patients. Results: During follow-up, the overall 5-year CSS rate was 81.4%. The 5-year CSS rates for patients with stage-I, -II, -III, and -IV RCC were 94.7%, 88.9%, 68.8%, and 19.3%, respectively. The patients with T1N0M0 (T1) and T2N0M0 (T2) tumors had similar survival curves. For patients with T1 category tumor, the survival rate did not differ significantly between the radical nephrectomy and nephron-sparing surgery groups. For the 21 patients with metastasis confined to the local lymph nodes, the 5-year survival rate was 31.6% after radical nephrectomy and lymph node dissection. For the 15 patients with vena caval tumor thrombus, the 5-year survival rate was 52.5% after radical nephrectomy and tumor thrombus extirpation. Multivariate Cox regression showed that stage was an independent predictor for CSS (hazard ratio, 3.359; P < 0.001). Conclusions: For localized RCC, the oncological outcome of this cohort is comparable to that reported in the Western literature. For some patients with locally advanced RCC, aggressive surgical treatment can lead to better long-term survival. However, the prognosis of the patients with metastasis still needs to be improved.

Survival analysis of children with stage Ⅱ testicular malignant germ cell tumors treated with surgery or surgery combined with adjuvant chemotherapy

For children with stage II testicular malignant germ cell tumors(MGCT), the survival is good with surgery and adjuvant chemotherapy. However, there is limited data on surgical results for cases in which there was no imaging or pathologic evidence of residual tumor, but in which serum tumor markers either increased or failed to normalize after an appropriate period of half-life time post-surgery. To determine the use of chemotherapy for children with stage II germ cell tumors, we analyzed the outcomes(relapse rate and overall survival) of patients who were treated at the Sun Yat-sen University Cancer Center between January 1990 and May 2013. Twenty-four pediatric patients with a median age of 20 months(range, 4 months to 17 years) were enrolled in this study. In 20 cases(83.3%), the tumors had yolk sac histology. For definitive treatment, 21 patients underwent surgery alone, and 3 patients received surgery and adjuvant chemotherapy. No relapse was observed in the 3 patients who received adjuvant chemotherapy, whereas relapse occurred in 16 of the 21 patients(76.2%) treated with surgery alone. There were a total of 2 deaths. Treatment was stopped for 1 patient, who died 3 months later due to the tumor. The other patient achieved complete response after salvage treatment, but developed lung and pelvic metastases 7 months later and died of the tumor after stopping treatment. For children treated with surgery alone and surgery combined with adjuvant chemotherapy, the 3-year event-free survival rates were 23.8% and 100%, respectively(P = 0.042), and the 3-year overall survival rates were 90.5% and 100%, respectively(P = 0.588). These results suggest that adjuvant chemotherapy can help to reduce the recurrence rate and increase the survival rate for patients with stage II germ cell tumors.

Complications of radical nephrectomy for renal cell carcinoma: a retrospective study comparing transperitoneal and retroperitoneal approaches using a standardized reporting methodology in two Chinese centers

The reporting of complications following transperitoneal and retroperitoneal open radical nephrectomy (RN) is nonstandardized. This study aimed to compare early complications between the two approaches using a standardized reporting methodology in a large contemporary cohort. Between 1996 and 2009, 558 patients underwent open RN for renal cell carcinoma (RCC) in our two centers (424 from Sun Yat-sen University Cancer Center and 134 from the First Affiliated Hospital of Sun Yat-sen University). Records were reviewed for clinicopathologic features and complications. Complications were graded using the Clavien system based on the severity of impact. One hundred and five patients (18.8%) had one or more early complications (168 complications overall). The overall rates of grades I to V complications were 5.6%, 10.8%, 2.2%, 0.4%, and 0.2%, respectively. Patients who underwent transperitoneal RN did not experience more overall or procedure-related complications than those who underwent retroperitoneal RN (P=0.911 and P=0.851, respectively). On subgroup analysis, neither grade I/II nor grades III-V complications were significantly different between the transperitonal RN and retroperitoneal RN groups. Multivariate analysis showed that for any grade of complication, age (P=0.016) and estimated blood loss (P=0.001) were significant predictors. We concluded that open RN is a safe procedure associated with low rates of serious morbidity and mortality. Compared with retroperitoneal RN, transperitoneal RN was not associated with more complications. Older patient and more blood loss at surgery were independent predictors for higher early postoperative complication rates.

Stage T1N0M0 renal cell carcinoma: the prognosis in Asian patients

The prognostic features of T1N0M0 renal cell carcinoma (RCC) in Asian patients have not been well explored in large sample studies. In this study, we retrospectively analyzed the records of 713 patients undergoing nephrectomy for T1N0M0 RCC between 1991 and 2009 in three Asian hospitals. Univariate and multivariate analysis were performed to identify the independent predictive factors for T1N0M0 RCC prognosis among a series of clinicopathological parameters, including age, gender, tumor size, Fuhrman grade, and histological classification. Our results showed that 388 of 713 patients had tumors 4.0 cm or smaller (stage T1a) and 325 of 713 patients had tumors 4.0-7.0 cm in size (stage T1b). Five-year cancer-specific survival (CSS) and recurrence-free survival (RFS) rates for this group of patients were 96.0% and 93.5%, respectively. The patients with T1b RCC had a significantly lower 5-year CSS and RFS rates than did those with T1a RCC (CSS, 93.1% vs. 98.6%, P = 0.026; RFS, 90.0% vs. 96.5%, P < 0.001). Patients with low grade (grades I-II) tumors had a higher 5-year CSS (97.8% vs. 91.2%, P = 0.001) and RFS (95.5% vs. 85.5%, P < 0.001) rate than did those with high grade (grades I-II) tumors. More interestingly, when stratifying patients to T1a and T1b groups, the role of grade in distinguishing prognosis could be only observed in patients with T1b disease. Cox regression showed tumor size and Fuhrman grade were significant in predicting CSS and RFS. Our study suggests that the prognosis of patients with T1N0M0 RCC is excellent, and these results are comparable to previously reported studies in Western patients. Furthermore, our data indicates that patients with T1b disease and high Fuhrman grade have high risk of tumor recurrence and death, thus requiring more frequent follow-up.

Radical cystectomy for bladder cancer: oncologic outcome in 271 Chinese patients

Few large scale studies have reported the oncologic outcome of radical cystectomy for treating bladder cancer in China; hence, we lack long-term prognostic information. The aim of the current study was to determine the survival rate and prognostic factors of patients who underwent radical cystectomy for bladder cancer in a Chinese medical center. We retrospectively analyzed clinicopathologic data from 271 bladder cancer patients who underwent radical cystectomy between 2000 and 2011. Univariate and multivariate analyses were conducted to identify independent prognostic predictors for this cohort. Median follow-up was 31.7 months(range, 0.2–139.1 months). Thirty-day mortality was(1.4%). The 5-year recurrence-free survival, cancer-specific survival(CSS), and overall survival rates were 61.6%, 72.9%, and 68.0%, respectively. The 5-year CSS rates of patients with T1–T4 disease were 90.7%, 85.0%, 51.0%, and 18.0%, respectively. Patients with organ-confined disease had a higher 5-year CSS rate than those with extravesical disease(81.4% vs. 34.9%, P < 0.001). For the 38 patients(14%) with lymph node involvement, the 5-year CSS rate was 27.7%—significantly lower than that of patients without lymph node metastasis(P < 0.001). The 5-year CSS rate was much higher in patients with low grade tumor than in those with high grade tumor(98.1% vs. 68.1%, P < 0.001). Multivariate Cox regression showed that patient age(hazard ratio, 2.045; P = 0.013) and T category(hazard ratio, 2.213; P < 0.001) were independent predictors for CSS. These results suggest that radical cystectomy is a safe and effective method for treating bladder cancer in Chinese patients. Old age and high T category were associated with poor prognosis in bladder cancer patients who underwent radical cystectomy.

Intraarterial chemotherapy with gemcitabine and cisplatin in locally advanced or recurrent penile squamous cell carcinoma

The prognosis of locally advanced or recurrent squamous cell carcinoma(SCC) of the penis after conventional treatment is dismal. This study aimed to evaluate the therapeutic effects of intraarterial chemotherapy with gemcitabine and cisplatin on locally advanced or recurrent SCC of the penis. Between April 1999 and May 2011, we treated 5 patients with locally advanced penile SCC and 7 patients with recurrent disease with intraarterial chemotherapy. The response rate and toxicity data were analyzed, and survival rates were calculated. After 2 to 6 cycles of intraarterial chemotherapy with gemcitabine and cisplatin, 1 patients with locoregionally advanced disease achieved a complete response, and 4 achieved partial response. Of the 7 patients with recurrent disease, 2 achieved complete response, 3 achieved partial response, 3 had stable disease, and 1 developed progressive disease. An objective tumor response was therefore achieved in 10 of the 12 patients. The median overall survival for the patients was 24 months(range, 10-50 months). Three out of 10 patients who responded were long-term survivors after intraarterial chemotherapy. Intraarterial chemotherapy with gemcitabine and cisplatin may be effective and potentially curative in locoregionally advanced or recurrent penile SCC. The contribution of this therapy in the primary management of advanced or recurrent penile SCC should be prospectively investigated.

Clinical outcomes in patients with stage non-seminomatous germ cell cancer

This study assesses the long-term outcomes in Han Chinese patients with clinical stage I non-seminomatous germ cell testicular cancer （CSI NSGCT） treated with surveillance, retroperitoneal lymph node dissection （RPLND） and adjuvant chemotherapy. We retrospectively evaluated 89 patients with a mean age of 26.5 years. After orchiectomy, 37 patients were treated with surveillance, 34 underwent RPLND and 18 were managed with chemotherapy. The overall survival rate, the recurrence-free survival rate and the risk factors were evaluated. The median follow-up length was 92 months （range： 6-149 months）. Thirteen of the 89 patients （14.6%） had relapses, and one died by the evaluation date. The overall survival rate was 98.9%. The cumulative 4-year recurrence-free rates were 80.2%, 92.0% and 100% for the surveillance, RPLND and chemotherapy groups, respectively. The disease-free period tended to be briefer in patients with a history of cryptorchidism and those with stage Is. Therefore, surveillance, RPLND and adjuvant chemotherapy might be reliable strategies in compliant patients with CSI NSGCT. Surveillance should be recommended for patients with the lowest recurrence rate, especially those without lymphovascular invasion. This study might aid the establishment of a standard therapy for CSI NSGCT in China.

阴茎癌改良临床病理肿瘤分期预后意义分析

背景与目的第8版美国癌症联合会-TNM(American Joint Committee on Cancer tumor–node–metastasis,AJCC-TNM)分期基于的是一些回顾性单中心研究。本研究旨在分析分期的预后价值,并探讨加入脉管癌栓的改良的临床病理肿瘤分期能否提高对T2–3期阴茎癌患者预后预测的准确性。方法根据第8版AJCC-TNM分期对2000年至2015年在中国和巴西2个中心接受治疗的411例患者所组成的训练队列进行分期。采用C-indexes一致性系数进行预测模型的评估,Bbootstrap再抽样法(1000次)进行模型验证。采用来自4个大洲15个中心接受治疗的436例患者的数据进行外部验证。结果根据第8版AJCC-TNM分期的T2和T3期患者有存活率重叠(P=0.587)。脉管癌栓是转移和生存的重要预后因素(均P <0.001)。多因素分析显示,仅脉管癌栓对癌症特异性生存(cancer-specific survival,CSS)有显著影响(风险比=1.587,95%置信区间=1.253–2.011;P=0.001)。发生脉管癌栓的T2和T3期患者的CSS显著短于无脉管癌栓的患者(P <0.001)。因此,我们提出一种改良的临床病理分期,将第8版AJCC-TNM分期的T2和T3期细分为如下2个新类别:T2期肿瘤侵犯尿道海绵体和/或阴茎海绵体和/或尿道且无淋巴管侵犯;T3期肿瘤侵犯尿道海绵体和/或阴茎海绵体和/或尿道并有淋巴管侵犯。加入脉管癌栓的改良的分期显示出预后分层改善,各组间CSS差异显著(均P <0.005),患者预后预测的准确性高于第8版AJCC-TNM分期(C-index,0.739 vs. 0.696)。以上结果在外部验证队列中得到了确认。结论 T2–3期阴茎癌是异质性的,加入脉管癌栓的改良临床病理分期比第8版AJCC-TNM分期对阴茎癌患者的预后预测能力更强。

Up-regulation of indoleamine 2,3-dioxygenase 1(IDO1)expression and catalytic activity is associated with immunosuppression and poor prognosis in penile squamous cell carcinoma patients

Background: Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan (Trp)catabolism have been demonstrated to play an important role in tumor immunosuppression. This study examined the expression and catalytic activity of IDO1 in penilesquamous cell carcinoma (PSCC) and explored their clinical significance.Methods: IDO1 expression level, serum concentrations of Trp and kynurenine (Kyn)were examined in 114 PSCC patients by immunohistonchemistry and solid-phaseextraction-liquid chromatography-tandem mass spectrometry. The survival was analyzed using Kaplan-Meier method and the log-rank test. Hazard ratio of death was analyzed via univariate and multivariate Cox regression. Immune cell types were definedby principal component analysis. The correlativity was assessed by Pearson’s correlation analysis.Results: The expression level of IDO1 in PSCC cells was positively correlatedwith serum Kyn concentration and Kyn/Trp radio (KTR;both P < 0.001) but negatively correlated with serum Trp concentration (P = 0.001). Additionally, IDO1 upregulation in cancer cells and the increase of serum KTR were significantly associated with advanced N stage (both P < 0.001) and high pathologic grade (P = 0.008and 0.032, respectively). High expression level of IDO1 in cancer cells and serumKTR were associated with short disease-specific survival (both P < 0.001). However, besides N stage (hazard radio [HR], 6.926;95% confidence interval [CI],2.458-19.068;P < 0.001) and pathologic grade (HR, 2.194;95% CI, 1.021-4.529;P = 0.038), only serum KTR (HR, 2.780;95% CI, 1.066-7.215;P = 0.036) was anindependent predictor for PSCC prognosis. IDO1 expression was positively correlated with the expression of interferon-𝛾 (IFN𝛾, P < 0.001) and immunosuppressivemarkers (programmed cell death protein 1, cytotoxic T-lymphocyte-associated protein 4 and programmed death-ligand 1 and 2;all P < 0.05), and the infiltration ofimmune cells (including cytotoxic T lymphocytes, regulatory T lymphocytes, tumorassociated macrophages, and myeloid-derived suppressor cells;all P < 0.001) inPSCC tissues. Furthermore, the expression of IDO1 was induced by IFN𝛾 in a dosedependent manner in PSCC cells.Conclusions: IFN𝛾-induced IDO1 plays a crucial role in immunoediting andimmunosuppression in PSCC. Additionally, serum KTR, an indicator of IDO1catabolic activity, can be utilized as an independent prognostic factor for PSCC.

A modified clinicopathological tumor staging system for survival prediction of patients with penile cancer

Background:The 8th American Joint Committee on Cancer tumor-node-metastasis(AJCC-TNM)staging system is based on a few retrospective single-center studies.We aimed to test the prognostic validity of the staging system and to determine whether a modified clinicopathological tumor staging system that includes lymphovascular emboliza-tion could increase the accuracy of prognostic prediction for patients with stage T2-3 penile cancer.Methods:A training cohort of 411 patients who were treated at 2 centers in China and Brazil between 2000 and 2015 were staged according to the 8th AJCC-TNM staging system.The internal validation was analyzed by bootstrap-corrected C-indexes(resampled 1000 times).Data from 436 patients who were treated at 15 centers over four conti-nents were used for external validation.Results:A survivorship overlap was observed between T2 and T3 patients(P=0.587)classified according to the 8th AJCC-TNM staging system.Lymphovascular embolization was a significant prognostic factor for metastasis and survival(all P<0.001).Based on the multivariate analysis,only lymphovascular embolization showed a significant influ-ence on cancer-specific survival(CSS)(hazard ratio=1.587,95%confidence interval=1.253-2.011;P=0.001).T2 and T3 patients with lymphovascular embolization showed significantly shorter CSS than did those without lymphovascu-lar embolization(P<0.001).Therefore,a modified clinicopathological staging system was proposed,with the T2 and T3 categories of the 8th AJCC-TNM staging system being subdivided into two new categories as follows:t2 tumors invade the corpus spongiosum and/or corpora cavernosa and/or urethra without lymphovascular invasion,and t3 tumors invade the corpus spongiosum and/or corpora cavernosa and/or urethra with lymphovascular invasion.The modified staging system involving lymphovascular embolization showed improved prognostic stratification with significant differences in CSS among all categories(all P<0.005)and exhibited higher accuracy in predicting patient prognoses than did the 8th AJCC-TNM staging system(C-index,0.739 vs.0.696).These results were confirmed in the external validation cohort.Conclusions:T2-3 penile cancers are heterogeneous,and a modified clinicopathological staging system that incorporates lymphovascular embolization may better predict the prognosis of patients with penile cancer than does the 8th AJCC-TNM staging system.