Adverse pathologic features impact survival outcomes for small renal masses following nephrectomy.

PURPOSE: While most small renal masses (SRM) < 4 cm have an excellent prognosis following resection, the impact of adverse T3a pathologic features on oncologic outcomes of SRMs remains unclear. We sought to compare clinical outcomes for surgically resected pT3a versus pT1a SRMs at our institution. MATERIALS AND METHODS: We retrospectively reviewed records of patients who underwent radical or partial nephrectomy (RN, PN) for renal tumors <4 cm at our institution between 2010 and 2020. We compared features and outcomes of pT3a vs pT1a SRMs. Continuous and categorical variables were compared using Student's t and Pearson's chi-squared tests, respectively. Postoperative outcomes of interest including overall, cancer-specific, and recurrence-free survival (OS, CSS, and RFS) were analyzed using Kaplan-Meier method, Cox proportional hazard regression, and competing risk analysis. Analyses were performed using R statistical package (R Foundation, v4.0). RESULTS: We identified 1,837 patients with malignant SRMs. Predictors of postoperative pT3a upstaging included higher renal score, larger tumor size, and presence of radiologic features concerning for T3a disease (odds ratio [OR] = 5.45, 95% confidence interval [CI] 3.92-7.59, P < 0.001). On univariable modeling, pT3a SRMs had higher positive margin rates (9.6% vs 4.1%, P < 0.001), worse OS (hazard ratio [HR] = 2.9, 95% CI 1.6-5.3, P = 0.002), RFS (HR 9.32, 95% CI 2-40.1, P = 0.003), and CSS (HR = 3.6, 95% CI 1.5-8.2, P = 0.003). On multivariable modeling, pT3a status remained associated with worse RFS (HR = 2.7, 95% CI 1.04-7, P = 0.04), but not OS (HR 1.6, 95% CI = 0.83-3.1, P = 0.2); multivariable modeling was deferred for CSS due to low event rates. CONCLUSIONS: Adverse T3a pathologic features portend worse outcomes for SRMs, highlighting the crucial role of pre-operative planning and case selection. These patients have relatively poor prognosis, and should be monitored more closely and counseled for consideration of adjuvant therapy or clinical trials.

Perivesical Fat Invasive Pattern as Prognostic Factor and Predictor of Response to Adjuvant Chemotherapy in T3 Stage Bladder Cancer.

BACKGROUND: The prognostic value of the distinction between microscopic (pT3a) and macroscopic (pT3b) perivesical fat invasions remains a subject of debate. To explore whether the pattern of perivesical fat invasion can serve as a prognostic factor to better subgroup T3 stage bladder cancer. MATERIALS AND METHODS: One hundred and forty-nine patients diagnosed with T3 stage bladder cancer at Sun Yat-sen University Cancer Center (SYSUCC) were selected for the experimental cohort in this study. Ninety-seven T3 stage bladder cancer patients with pathological slices at the Cancer Genome Atlas (TCGA) were selected as validation cohort in this study. The perivesical fat invasive pattern was examined with hematoxylin and eosin-stained pathological slides by two pathologists independently. Two different perivesical fat invasive patterns, fibrous-surrounded (FS) pattern, and nonfibrous-surrounded (NFS) pattern were assessed. RESULTS: Perivesical fat invasion pattern had a significant influence on overall survival in T3 stage bladder cancer. Compared to the NFS pattern, the FS pattern was related to a better prognosis in both the SYSUCC cohort and TCGA cohort. The patients with NFS pattern tumor who underwent cisplatin-based adjuvant chemotherapy experienced an obvious improvement compared to observation after radical cystectomy in overall survival in the SYSUCC cohort. CONCLUSION: The perivesical fat invasion pattern could predict prognosis and clinically different chemotherapeutic survival outcomes in patients with T3 stage bladder cancer after radical cystectomy.

Residual cancer is a strong predictor of survival in T3 incidental gallbladder cancer.

BACKGROUND AND PURPOSE: Index cholecystectomy is insufficient for curing T3 incidental gallbladder cancer (IGC), and once residual cancer (RC) is found, the prognosis is often poor. The purpose of this study was to investigate the effect of RC on the prognosis and the optimal choice of adjuvant therapy for R0 reresection patients with T3 IGC. METHODS: We retrospectively reviewed data from patients with T3 IGC who underwent radical reresection from January 2013 to December 2018. RC was defined as histologically proven cancer at reresection. Demographics and tumour treatment-related variables were analysed in correlation with RC and survival. Adjuvant (Adj) chemoradiotherapy (CRT) was correlated with overall survival (OS) and disease-free survival (DFS). RESULTS: Of the 167 patients with IGC who underwent surgery, 102 underwent radical extended resection. Thirty-two (31.4%) RCs were found. Hepatic side tumours (T3h) and both side tumours (T3h + T3p) were associated with the presence of RC. In multivariate analysis, RC and lymph node metastasis were independent prognostic factors for DFS and OS (P < 0.05). RC was associated with a significantly shorter median OS (20 vs. 53 months; P < 0.01) and DFS (11 vs. 40 months; P < 0.001) despite R0 resection. For R0 reresection patients with RC and/or lymph node metastasis, Adj CRT significantly improved OS (P = 0.024). CONCLUSION: Residual cancer and lymphatic metastasis are important factors for the poor prognosis of T3 IGC despite R0 resection, and these patients should actively receive adjuvant therapy.

Laparoscopic segment 4b+5 liver resection for stage T3 gallbladder cancer.

BACKGROUND: There is still controversy over whether to perform laparoscopic surgery for T3 stage gallbladder cancer. In addition, the necessity of segment 4b+5 liver resection for stage T3 gallbladder has not been reported. This article aims to explore the safety, effectiveness, and short-term prognosis of laparoscopic segment 4b+5 liver resection for T3 stage gallbladder cancer. METHODS: This is a retrospective multicenter propensity score-matched study. Disease-free survival, perioperative complications, and intraoperative safety were analyzed to evaluate safety and effectiveness. RESULTS: There was no significant difference in the incidence of intraoperative bleeding, number of lymph nodes obtained, postoperative complications, or disease-free survival (DFS) between the open group (OG) and laparoscopic group (LG) (P > 0.05). The DFS time of the S4b+5 resection group (S4b5) was longer than that of the wedge group (P = 0.016). Cox regression showed that positive margins (HR, 5.32; 95% CI 1.03-27.63; P = 0.047), lymph node metastasis (HR, 2.70; 95% CI 1.31-5.53; P = 0.007), and liver S4b+5 resection (HR, 0.30; 95% CI 0.14-0.66; P = 0.003) were independent risk factors for DFS. The operative time of indocyanine green (ICG) fluorescence-guided liver S4b5 segment resection was shorter than that of traditional laparoscopic S4b+5 resection guided by hepatic veins (P ≤ 0.001). CONCLUSION: Laparoscopic liver S4b+5 resection for T3 stage gallbladder cancer is safe and feasible and can prolong DFS. ICG fluorescence-guided negative staining may reduce the difficulty of the operation.

Stage cT3 low rectal cancer: analysis of prognostic factors.

Background: Whether all cT3 low rectal cancer patients should receive neoadjuvant chemoradiotherapy (nCRT) remains controversial. The depth of invasion beyond the muscularis propria of the cT3 rectal cancer is of great significance to the selection of a treatment plan and the evaluation of prognosis. Methods: A retrospective analysis was conducted of 187 patients with stage cT3 low rectal cancer, who had been treated at the Department of Colorectal Surgery, The First Affiliated Hospital of Xiamen University from June 2010 to December 2012. The patients were divided into the nCRT group (88 cases) and no-nCRT group (99 cases). Possible significant prognostic factors [i.e., primary tumor volume (PTV), cell differentiation, circumferential resection margin (CRM), nCRT, age, sex, carcinoembryonic antigen (CEA), lymph node status, surgical procedure, etc.] were collected for estimation of disease-free survival (DFS), distant metastases rate (DM), local recurrence rate (LR). Independent predictive factors or survival were determined using Cox proportional hazards model. Results: The mean PTV was 16.2±11.1 (2.07-72.68) cm3. In the univariate and multivariate analyses: nCRT hazards ratio (HR) =4.258, 95% confidence interval (CI): 1.912-9.483 (P<0.001); PTV HR =0.381, 95% CI: 0.181-0.804 (P=0.011); CRM HR =0.227, 95% CI: 0.097-0.532 (P=0.001). For the PTV ≤15 cm3 group, there were no significant differences between the nCRT and no-nCRT group in 3-year follow-up (P>0.05). For the PTV >15 cm3 group, there were significant differences between the nCRT and no-nCRT group in 3-year DFS (84.2% vs. 51.1%; P=0.001), DM (13.1% vs. 31.2%; P=0.017) and LR (2.9% vs. 26.6%; P=0.009). For the CRM negative group, there were significant differences between the nCRT and no-nCRT group in 3-year DFS (94.0% vs. 79.0%; P=0.008), LR (1.5% vs. 10.7%; P=0.028) and DM (4.5% vs. 13.5%; P=0.039). Conclusions: For stage cT3 low rectal cancer patients, nCRT, PTV, and CRM were independent prognostic factors. NCRT may improve the survival of PTV >15 cm3 patients, but may not have a significant effect on patient with PTV ≤15 cm3 and CRM negative. Direct surgery is recommended for this group of patients.

Better prognostic determination of cT3 rectal cancer through measurement of distance to mesorectal fascia: A multicenter study.

OBJECTIVE: To forward the magnetic resonance imaging (MRI) based distance between the deepest tumor invasion and mesorectal fascia (DMRF), and to explore its prognosis differentiation value in cT3 stage rectal cancer with comparison of cT3 substage. METHODS: This was a retrospective, multicenter cohort study including cT3 rectal cancer patients undergoing neoadjuvant chemoradiotherapy followed by radical surgery from January 2013 to September 2014. DMRF and cT3 substage were evaluated from baseline MRI. The cutoff of DMRF was determined by disease progression. Multivariate cox regression was used to test the prognostic values of baseline variables. RESULTS: A total of 804 patients were included, of which 226 (28.1%) developed progression. A DMRF cutoff of 7 mm was chosen. DMRF category, the clock position of the deepest position of tumor invasion (CDTI) and extramural venous invasion (EMVI) were independent predictors for disease progression, and hazard ratios (HRs) were 0.26 [95% confidence interval (95% CI), 0.13-0.56], 1.88 (95% CI, 1.33-2.65) and 1.57 (95% CI, 1.13-2.18), respectively. cT3 substage was not a predictor for disease progression. CONCLUSIONS: The measurement of DMRF value on baseline MRI can better distinguish cT3 rectal cancer prognosis rather than cT3 substage, and was recommended in clinical evaluation.

Mortality Increases When Radical Nephrectomy is Delayed More Than 60 Days for T3 Renal Cell Carcinoma.

Background: Radical nephrectomy is widely accepted as the default management option for patients with T3 renal cell carcinoma (RCC). However, it may require a certain time before surgery for various reasons. There are concerns that the delay in surgery may affect postoperative outcomes. The present study aimed to evaluate the impact of surgical wait time on survival in patients with T3 RCC. Methods: We retrospectively selected 138 patients with T3 RCC who underwent radical surgery between July 2009 and December 2019. Surgical wait time was defined as the period from initial imaging diagnosis to surgery. Patients were divided into the following 2 groups according to wait time: short-wait group(≤60 days), and long-wait group (>60 days). The clinical and pathological characteristics were evaluated. The overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) of each group were calculated and compared. Age, gender, interval, tumor size, pathological grade, Eastern Cooperative Oncology Group performance status (ECOG PS), surgical approach, year of surgery, and pathological type were included in the multivariable model. Results: This study included 91 male (65.9%) and 47 female (34.1%) patients. The median age of all patients was 60 years (interquartile range [IQR] 52-68 years). The median body mass index is 22.2 kg/m2 (IQR 18.9-24.7  kg/m2). There were 128 patients (92.8%) with pT3a disease and 10 patients (7.3%) with pT3b disease. The median surgical wait time for all patients was 16 days (IQR 10-77 days). The median surgical wait time of the short- and long-wait groups was 12 days (IQR 8-16 days) and 92 days (IQR 79-115 days), respectively. Until the last follow-up, 54 patients died. Among them, 49 patients (90.7%) died of tumor-related causes, and 5 patients (9.3%) died of other causes. There are 1 and 4 cases in the short-wait and long-wait groups, respectively. There were no significant differences in gender, ECOG PS, American society of anesthesiologists score, Charlson comorbidity index, clinical T stage, clinical N stage, and body mass index. And there were no significant differences in tumor size, surgical approach, year of surgery, pathological type, tumor grade, pathological T stage, pathological N stage, and venous involvement between the 2 groups. OS, CSS, and RFS were compared. The 5-year OS of the short- and long-wait time groups were 65.0% and 40.9%, respectively (P = .030). The 5-year CSS rates of the short- and long-wait time groups were 68.7% and 51.5%, respectively (P = .012). The 5-year RFS rates of the short- and long-wait time groups were 61.5% and 46.8%, respectively (P = .119). Multivariable analysis revealed that surgical wait time interval and tumor size were independent risk factors for OS and that wait time was also an independent risk factor for CCS. Conclusion: Delay in radical surgery beyond 60 days can negatively affect OS in patients with T3 RCC.

High expression of EGFR predicts poor survival in patients with resected T3 stage gastric adenocarcinoma and promotes cancer cell survival.

Epidermal growth factor receptor (EGFR) is an essential regulator and biomarker of several types of cancer. However, the association between its expression and prognosis in patients with resected T3 stage gastric adenocarcinoma (RT3-GA) remains to be determined. In total, 683 patients with resectable T3-GA who underwent surgery were retrospectively included in the present study, and their immunohistochemical data for EGFR expression were collected. The associations between the patients' clinicopathologic characteristics and EGFR immunohistochemistry data were analyzed by multiple statistical methods. Annexin V apoptosis and MTT cell viability assays were performed to explore the effect of EGFR on AGS gastric adenocarcinoma cell survival. EGFR expression levels were categorized into two groups: low (406 cases) and high (277 cases). High EGFR was demonstrated to be significantly associated with distant metastasis (P=0.043) and severely decreased median overall survival time (MOST) and recurrence-free survival time (MRFST). MOST and MRFST in the low EGFR group were 39 and 37 months, respectively; whereas in the high EGFR group these values were only 18 and 13 months (P=3.10×10-9 and P=6.74×10-8, respectively). Multivariate analysis confirmed that high EGFR expression levels were associated with poor survival, which was associated with significantly increased recurrence risk and ~2-fold elevation in mortality risk [hazard ratio (HR), 1.73; 95% confidence interval (CI), 1.43-2.10; P=2.37×10-8 and HR, 1.80; 95% CI, 1.50-2.17; P=3.80×10-10]. Inhibiting EGFR with AG1478 suppressed its effect on promoting AGS cell survival. These results suggest that high EGFR expression indicates poor survival in patients with RT3-GA, which may be correlated with EGFR promoting GA cell survival.

Oncological outcomes of cryosurgery as primary treatment in T3 prostate cancer: experience of a single centre.

OBJECTIVE: To assess the oncological outcomes and determine prognostic factors for overall survival (OS), cancer-specific survival (CSS), and biochemical progression-free survival (BPFS) after cryosurgery for clinical stage T3 prostate cancer. PATIENTS AND METHODS: Between 2002 and 2007, 75 patients with clinical stage T3 prostate cancer received cryosurgery as primary treatment in our institution. No adjuvant treatment was provided until biochemical failure. After biochemical failure, hormone therapy was administered. Kaplan-Meier analysis was used to calculate the OS, CSS, and BPFS. Cox regression was used to identify factors predictive of survival. RESULTS: Clinical stage T3a (cT3a) was detected in 60% (45/75) of patients and cT3b detected in 40% (30/75). The 5-year OS, CSS, and BPFS rates were 85.3%, 92.0%, and 48%, respectively. There was a significant difference when comparing the pT3a with the pT3b group for 5-year OS (88.9% vs 80%, P = 0.02) and BPFS (55.6% vs 36.7%, P = 0.01), but there was no difference in CSS (93.3% vs 90%, P = 0.63). Stage, Gleason score, and nadir prostate-specific antigen (PSA) were associated with BPFS, while Gleason score and nadir PSA were the most significant predictors for CSS. CONCLUSIONS: Cryosurgery can offer good 5-year OS, CSS, and BPFS rates for cT3 prostate cancer, and there was no difference between T3a and T3b for CSS. Gleason score and nadir PSA were the most significant predictors of survival. Further clinical trials are warranted for evaluating the role of cryosurgery for cT3 prostate cancer.