Prognostic significance of serum lactate dehydrogenase in patients undergoing radical cystectomy for bladder cancer

BackgroundTo investigate the prognostic significance of preoperative serum lactate dehydrogenase (LDH) in patients undergoing radical cystectomy for bladder cancer (BCa).Patients and methodsA cohort of 263 patients undergoing open or laparoscopic radical cystectomy between 2011 and 2016 was studied. Baseline characteristics, hematological variables, follow-up data were collected. Kaplan-Meier curves and Cox proportional hazard regression model were applied to assess the relationship between LDH and overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS).ResultsAfter a median 34.2 (22.9–45.8) months follow-up, all-cause death, cancer-specific death, and disease recurrence occurred in 66 patients, 50 patients, and 91 patients. The elevation of serum LDH was associated with several unfavorable parameters, including advanced age, continent cutaneous urinary diversion, increased neutrophil-to-lymphocyte ratio, decreased lymphocyte-to-monocyte ratio. Patients with a higher serum LDH (> 220 U/L) had a worse OS (P < 0.001), CSS (P < 0.001) and DFS (P < 0.001). Multivariate Cox analysis suggested that elevated LDH was an independent predictor for OS (hazard ratio [HR]: 3.113, 95% confidence interval [CI]: 1.524–6.358; P = 0.002), CSS (HR: 4.564, 95% CI: 2.008–10.373; P < 0.001), DFS (HR: 2.051, 95% CI: 1.125–3.739; P = 0.019). Medical history of diabetes, high pT stage, and positive lymph node also were adverse predictors for oncological outcomes of BCa patients in multivariate analysis.ConclusionsPreoperative serum LDH is an independent prognostic biomarker for OS, CSS, and DFS in patients undergoing radical cystectomy for BCa, which can be incorporated into prognostic models.     

Prognostic nutritional index and prognosis in renal cell carcinoma: A systematic review and meta-analysis

PurposeTo perform a systematic review and meta-analysis of the Prognostic Nutritional Index (PNI) as a prognostic factor for renal cell carcinoma (RCC).Materials and methodsEligible studies that evaluated the prognostic impact of pretreatment PNI in RCC patients were identified by comprehensive searching the electronic databases PubMed, Cochrane Central Search library, and EMBASE. The end points were overall/cancer-specific survival (OS/CSS) and recurrence-free/disease-free survival (RFS/DFS). Meta-analysis using random-effects models was performed to calculate hazard ratios (HRs) with 95 % confidence intervals (CIs).ResultsIn total, 9 retrospective, observational, case-control studies involving 5,976 patients were included for final analysis. Eight studies evaluated OS/CSS, and 5 evaluated RFS/DFS. Our results showed that lower PNI was significantly associated with unfavorable OS/CSS (HR = 1.68, 95% CI 1.44-1.96, P < 0.001, I² = 9.2%, P = 0.359) and RFS/DFS (HR = 1.98, 95% CI 1.57-2.50, P < 0.001, I² = 18.2%, P = 0.299) in patients with RCC. Subgroup and meta-regression analysis based on ethnicity, study sample size, presence of metastasis, PNI cut-off value, Newcastle–Ottawa quality assessment scale (NOS) score, and gender ratio all showed that lower PNI was associated with poorer OS/CSS and RFS/DFS. Funnel plots and Egger's tests indicated significant publication bias in OS/CSS (P = 0.001), but not in RFS/DFS (P = 0.757).ConclusionThis meta-analysis indicated that lower PNI was a negative prognostic factor and associated with tumor progression and poorer survival of patients with RCC. Therefore, PNI could be a potential prognostic predictor of treatment outcomes for patients with RCC.     

Oncologic safety of minimally invasive surgery in non-endometrioid endometrial cancer

ObjectiveThis study was aimed to compare the oncologic outcomes of patients with non-endometrioid endometrial cancer who underwent minimally invasive surgery with the outcomes of patients who underwent open surgery.MethodThis is a retrospective, multi-institutional study of patients with non-endometrioid endometrial cancer who were surgically staged by either minimally invasive surgery or open surgery. Oncologic outcomes of the patients were compared according to surgical approach.Results113 patients met the inclusion and exclusion criteria. 57 underwent minimally invasive surgery and 56 underwent open surgery. Patients who underwent minimally invasive surgery had smaller tumors (median size, 3.3 vs. 5.2%, p = 0.0001) and a lower lymphovascular space invasion rate (29.8% vs. 48.2%, p = 0.045). In the overall population, the numbers and rate of recurrence were significantly higher in the open surgery group (p = 0.016). In multivariate analysis, disease stage and tumor size were associated with DFS in contrast to surgical procedure.ConclusionMinimally invasive surgery showed similar survival outcomes when compared to open surgery in non-endometrioid endometrial cancer patients, irrespective of disease stage. When minimally invasive surgery is managed by expert surgeons, non-endometrioid histological subtypes should not be considered a contraindication for minimally invasive surgery.     

Effect of concomitant variant histology on the prognosis of patients with upper urinary tract urothelial carcinoma after radical nephroureterectomy

ObjectiveTo evaluate the prognostic effect of concomitant variant histology (CVH) on survival outcomes in patients with upper urinary tract urothelial carcinoma (UTUC) after radical nephroureterectomy.Materials and methodsData on 417 patients with UTUC treated with radical nephroureterectomy without preoperative adjuvant therapy were retrospectively reviewed with a focus on CVH. Clinicopathological features and prognostic factors were compared between patients with pure UTUC and patients with UTUC with CVH. The primary end points were cancer-specific survival (CSS), disease recurrence-free survival (DFS), and overall survival (OS).ResultsUTUC with CVH was present in 90 (21.6%) of 417 patients. At a median follow-up of 26 months, 153 (36.7%) had died of UTUC, 161 (38.6%) had experienced a relapse, and 176 (42.2%) had died of other causes. UTUC with CVH was significantly associated with advanced tumor stage, high tumor grade, tumor diameter, lymphovascular invasion, lymph node metastasis, positive surgical margins, and tumor architecture compared with pure UTUC (all P<0.01). The estimated 5-year CSS, DFS, and OS rates were 64.9%, 61.1%, and 62.1%, respectively, in the pure UTUC group, compared with 36.3%, 34.3%, and 26.5%, respectively, in the UTUC with CVH group (P<0.001). Multivariate analysis demonstrated that CVH was an independent predictor of CSS (hazard ratio [HR] = 1.594; 95% CI: 1.125–2.259; P = 0.009), DFS (HR = 1.549; 95% CI: 1.077–2.152; P = 0.017), and OS (HR = 1.685; 95% CI: 1.212–2.343; P = 0.002).ConclusionsApproximately one-fifth of the specimens of patients with UTUC were observed to exhibit CVH. CVH was an independent prognostic factor for CSS, DFS, and OS in patients with UTUC on both univariate and multivariate analyses. Genitourinary pathologists should look for potential CVH components in UTUC specimens and report this in routine pathological practice. The presence of CVH should identify patients as candidates for consultation regarding early adjuvant therapy and intensive surveillance protocols.     

Association between lymphovascular invasion and oncological outcome in node-negative upper tract urothelial carcinoma with different stage

ObjectivesTo evaluate the prognostic impact of lymphovascular invasion (LVI) on node-negative upper tract urothelial carcinoma (UTUC) in patients treated with radical nephroureterectomy (RNU).Materials and methodsA retrospective study was performed in single tertiary referral center of middle Taiwan between 2001 and 2015. Seven hundred and twenty-eight patients were diagnosed of UTUC and underwent RNU with ipsilateral bladder cuff excision including 303 and 195 patients with N0 and Nx status respectively. LVI status was assessed as a prognostic factor for cancer-specific (CSS) and overall survival (OS) using univariate and multivariate Cox regression analysis.ResultsLVI was observed in 82 patients (16.5%). LVI presentation associated with smoking status, advanced tumor stage, high tumor grade, positive surgical margin, and consequence lung/liver/bone metastasis. In the multivariate analysis, LVI was failed to predict CSS, OS, and disease-free survival (DFS) (hazard ratio [HR] [95% confidence interval [CI]: 1.07 [0.55–2.09], 1.05 [0.62–1.79], 1.15 [0.69–1.92], in CSS, OS, DFS, respectively). In the subgroup analysis of pT1-2 disease, the CSS, OS, and DFS were associated with LVI status (HR [95% CI]: 2.29 [0.44–11.84], 3.17 [1.16–8.67], 2.66 [1.04–6.79], in CSS, OS, DFS, respectively). In contrast, there was no difference in pT3 disease.ConclusionIn conclusion, LVI status was not associated with survival outcomes of node-negative UTUC in our study. The subgroup analysis showed different prognostic impacts of LVI status in node-negative UTUC with T1-2 and T3 stage. Further evidence to clarify the prognostic effect is needed to make LVI became a practical factor in clinical decision-making.     

Prognostic effect of preoperative serum albumin to globulin ratio in patients treated with cytoreductive nephrectomy for metastatic renal cell carcinoma

BackgroundAccurate identification of ideal candidates for cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) is an unmet need. We tested the association between preoperative value of systemic albumin to globulin ratio (AGR) and overall survival (OS) as well as cancer-specific survival (CSS) in mRCC patients treated with CN.MethodsmRCC patients treated with CN were included. The overall population was therefore divided into two AGR groups using cut-off of 1.43 (low, <1.43 vs. high, ≥1.43). Univariable and multivariable Cox regression analyses tested the association between AGR and OS as well as CSS. The discrimination of the model was evaluated with the Harrel’s concordance index (C-index). The clinical value of the AGR was evaluated with decision curve analysis (DCA).ResultsAmong 613 mRCC patients, 159 (26%) patients had an AGR <1.43. Median follow-up was 31 (IQR: 16–58) months. On univariable analysis, low preoperative serum AGR was significantly associated with both OS (HR: 1.55, 95% CI: 1.26–1.89, P<0.001) and CSS (HR: 1.55, 95% CI: 1.27–1.90, P<0.001). On multivariable analysis, AGR <1.43 was associated with worse OS (HR: 1.51, 95% CI: 1.23–1.85, P<0.001) and CSS (HR: 1.52, 95% CI: 1.24–1.86, P<0.001). The addition of AGR only minimally improved the discrimination of a base model that included established clinicopathologic features (C-index=0.640 vs. C-index=0.629). On DCA, the inclusion of AGR marginally improved the net benefit of the prognostic model. Low AGR remained independently associated with OS and CSS in the IMDC intermediate risk group (HR: 1.52, 95% CI: 1.16–1.99, P=0.002).ConclusionsIn our study, low AGR before CN was associated with worse OS and CSS, particularly in intermediate risk patients.     

Neoadjuvant and Adjuvant Chemotherapy for Upper Tract Urothelial Carcinoma: A 2020 Systematic Review and Meta-analysis,and Future Perspectives on Systemic Therapy

ContextTo improve the prognosis of upper tract urothelial carcinoma (UTUC), clinicians have used neoadjuvant chemotherapy (NAC) or adjuvant chemotherapy (AC) before or after radical nephroureterectomy (RNU). Despite some new data, the evidence remains mixed on their efficacy.ObjectiveTo update the current evidence on the role of NAC and AC for UTUC.Evidence acquisitionWe searched for all studies investigating NAC or AC for UTUC in Medline, Embase, the Cochrane Central Register of Controlled Trials, and abstracts from the American Society of Clinical Oncology meetings up to February 2020. A systematic review and meta-analysis was performed.Evidence synthesisFor NAC, the pooled pathologic complete response rate (≤ypT0N0M0) was 11% (n = 811) and pathologic partial response rate (≤ypT1N0M0) was 43% (n = 869), both across 14 studies. Across six studies, the pooled hazard ratios (HRs) were 0.44 (95% confidence interval [CI]: 0.32–0.59, p < 0.001) for overall survival (OS) and 0.38 (95% CI: 0.24–0.61, p < 0.001) for cancer-specific survival (CSS) in favor of NAC. The evidence for NAC is at best level 2. As for AC, there was a benefit in OS (pooled HR 0.77; 95% CI: 0.64–0.92, p = 0.004 across 14 studies and 7983 patients), CSS (pooled HR 0.79; 95% CI: 0.69–0.91, p = 0.001 across 18 studies and 5659 patients), and disease-free survival (DFS; pooled HR 0.52; 95% CI: 0.38–0.70 across four studies and 602 patients). While most studies were retrospective (level 2 evidence), there were two prospective randomized trials providing level 1 evidence. There are currently four phase 2 trials on neoadjuvant immunotherapy and three phase 2 trials on adjuvant immunotherapy for UTUC.ConclusionsNAC for UTUC confers a favorable pathologic response and tumor downstaging rate, and an OS and CSS benefit compared with RNU alone. AC confers an OS, CSS, and DFS benefit compared with RNU alone. Currently, the evidence for AC appears stronger (with positive level 1 evidence) than that for NAC (at best level 2 evidence). Limited data are available for chemoimmunotherapy approaches, but preliminary data support an active research investment.Patient summaryAfter a comprehensive search of the latest studies examining the role of neoadjuvant and adjuvant chemotherapy for upper tract urothelial cancer, the pooled evidence shows that perioperative chemotherapy was beneficial for prolonging survival; however, the evidence for adjuvant chemotherapy was stronger than that for neoadjuvant chemotherapy.     

Whether histologic subtyping affect the oncological outcomes of patients with papillary renal cell carcinoma: evidence from a systematic review and meta-analysis

BackgroundWhether the histologic subtype (type 1 and type 2) of papillary renal cell carcinoma (pRCC) is a tool to predict the prognosis is of great debate. This study is aimed to evaluate the prognostic significance of histologic subtype in patients with pRCC after surgery through a systematic review and meta-analysis.MethodsWe searched PubMed, the Web of Science, Cochrane library and EMBASE databases to identify studies published until January 20, 2021 according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Studies were deemed eligible if they compared the overall survival (OS), cancer specific survival (CSS), recurrence-free survival (RFS) or disease-free survival (DFS) between patients with type 1 or type 2 pRCC. And the corresponding hazard ratios (HRs) and 95% conference intervals (CIs) were collected for meta-analysis and further subgroup analysis.ResultsOverall 22 studies with a total of 4,494 patients were considered eligible and included for the systematic review and meta-analysis. The pooled results showed that type 2 pRCC was associated with a worse OS (pooled HR 1.61, 95% CI: 1.10–2.36, P=0.02) and CSS (pooled HR 1.59, 95% CI: 1.00–2.51, P=0.05). However, the subgroup analysis yielded the same result as the initial analysis only when the HRs were extracted from univariate analysis. In studies with multivariate analysis, type 2 pRCC was not statistically associated with a worse OS (pooled HR 1.22, 95% CI: 0.97–1.53, P=0.27), CSS (pooled HR 1.16, 95% CI: 0.67–2.00, P=0.60), and DFS (pooled HR 1.33, 95% CI: 0.93–1.91, P=0.12) compared to type 1 pRCC.DiscussionHistologic subtype is not an independent prognostic factor for patients with pRCC, although the result needs to be taken with caution. And studies with retrospective study design, larger sample size and longer follow-up period are required to verify these results.     

Association of preoperative serum De Ritis ratio with oncological outcomes in patients treated with cytoreductive nephrectomy for metastatic renal cell carcinoma

PurposeIdentifying which patients are likely to benefit from cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) is important. We tested the association between preoperative serum De Ritis ratio (DRR, Aspartate Aminotransferase/Alanine Aminotransferase) and overall survival (OS) as well as cancer-specific survival (CSS) in mRCC patients treated with CN.Material and methodsmRCC patients treated with CN at different institutions were included. After assessing for the optimal pretreatment DRR cut‐off value, we found 1.2 to have the maximum Youden index value. The overall population was therefore divided into 2 DRR groups using this cut‐off (low, <1.2 vs. high, ≥1.2). Univariable and multivariable Cox regression analyses tested the association between DRR and OS as well as CSS. The discrimination of the model was evaluated with the Harrel's concordance index (C-index). The clinical value of the DRR was evaluated with decision curve analysis.ResultsAmong 613 mRCC patients, 239 (39%) patients had a DRR ≥1.2. Median follow-up was 31 (IQR 16–58) months. On univariable analysis, high DRR was significantly associated with OS (hazard ratios [HR]: 1.22, 95% confidence interval [CI]: 1.01–1.46, P = 0.04) and CSS (HR: 1.23, 95% CI: 1.02–1.47, P = 0.03). On multivariable analysis, which adjusted for the effect of established clinicopathologic features, high DRR remained significantly associated with both OS (HR: 1.26, 95% CI: 1.04-1.52, P = 0.02) and CSS (HR: 1.26, 95% CI: 1.05–1.53, P = 0.01). The addition of DRR only minimally improved the discrimination of a base model that included established clinicopathologic features (C-index = 0.633 vs. C-index = 0.629). On decision curve analysis, the inclusion of DRR did not improve the net-benefit beyond that obtained by established subgroup analyses stratified by IMDC risk groups, type of systemic therapy, body mass index and sarcomatoid features, did not reveal any prognostic value to DRR.ConclusionDespite the statistically significant association between DRR and OS as well as CSS in mRCC patients treated with CN, DRR does not seem to add any further prognostic value beyond that obtained by currently available features.     

Internal mammary node irradiation in node-positive breast cancer treated with mastectomy and taxane-based chemotherapy

BackgroundIt is important to continually reevaluate the risk/benefit calculus of internal mammary node irradiation (IMNI) in the era of modern systemic therapy. We aimed to investigate the effect of IMNI on survival in node-positive breast cancer treated with mastectomy and anthracycline plus taxane-based chemotherapy.MethodsWe analyzed 348 patients who underwent mastectomy and anthracycline plus taxane-based chemotherapy for node-positive breast cancer between January 2006 and December 2011. All patients received postoperative radiation therapy (RT) with IMNI (n = 105, 30.2%) or without IMNI (n = 243, 69.8%). The benefit of IMNI for disease-free survival (DFS) and overall survival (OS) was evaluated using multivariate analysis and inverse probability of treatment weighting (IPTW) to adjust for unbalanced covariates between the groups.ResultsAfter a median follow-up of 95 months, the 10-year locoregional recurrence-free survival rate, DFS, and OS in all patients were 94.8%, 77.4%, and 86.2%, respectively. The IPTW-adjusted hazard ratio (HR) for the association of IMNI (vs. no IMNI) with DFS and OS was 0.208 (95% confidence intervals (CI) 0.045–0.966) and 0.460 (95% CI, 0.220–0.962), respectively. In multivariate analysis, IMNI was a favorable factor for DFS (HR, 0.458; P = 0.021) and OS (HR 0.233, P = 0.018).ConclusionsIMNI was associated with improved DFS and OS in node-positive patients treated with mastectomy, post-mastectomy RT, and taxane-based chemotherapy, although the rate of locoregional recurrence was low.     

Evaluation of the platelet-to-lymphocyte ratio as a prognostic indicator in a European cohort of patients with prostate cancer treated with radiotherapy

ObjectivesRecent evidence suggests that the presence of a systemic inflammatory response plays an important role in the progression of several solid tumors. The platelet-to-lymphocyte ratio (PLR) has been proposed as an easily assessable marker of systemic inflammation and has been shown to represent a prognostic marker in different cancer entities. To evaluate the prognostic value of the PLR in prostate cancer, we performed the present study.Methods and materialsData from 374 consecutive patients with prostate cancer, treated with 3D conformal radiotherapy from 1999 to 2007, were analyzed. Distant metastases–free survival (MFS), cancer-specific survival (CSS), overall survival (OS), biochemical disease–free survival, and time to salvage systemic therapy were assessed using the Kaplan-Meier method. Cox proportional hazards analysis was performed to calculate hazard ratio (HR) and 95% CI. Multivariate Cox regression analysis was performed to adjust for other covariates.ResultsUsing receiver operating characteristics analysis, the optimal cutoff level for the PLR was 190. Kaplan-Meier analyses revealed that PLR≥190 was a prognostic factor for decreased MFS (P = 0.004), CSS (P = 0.004), and OS (P = 0.024) whereas a significant association of an elevated PLR with biochemical disease–free survival (P = 0.740) and time to salvage systemic therapy (P = 0.063) was not detected. In multivariate analysis, an increased PLR remained a significant prognostic factor for poor MFS (HR = 2.24, 95% CI: 1.06–4.76, P = 0.036), CSS (HR = 3.99, 95% CI: 1.19–13.4, P = 0.025), and OS (HR = 1.87, 95% CI: 1.02–3.42, P = 0.044).ConclusionsOur findings indicate that the PLR may predict prognosis in patients with prostate cancer and may contribute to future individual risk assessment in them.     

Is hepatic resection justified for non-colorectal non-neuroendocrine liver metastases? A systematic review and meta-analysis

BackgroundHepatic resection (HR) is effective for colorectal or neuroendocrine liver metastases. However, the role of HR for non-colorectal non-neuroendocrine liver metastases (NCNNLM) is unknown. This study aims to perform a systematic review and meta-analysis on long-term clinical outcomes after HR for NCNNLM.Methodselectronic search was performed to identify relevant publications using PRISMA and MOOSE guidelines. Primary outcomes were 3- and 5-year overall survival (OS) and disease-free survival (DFS). Secondary outcomes were post-operative morbidity and 30-day mortality.ResultsThere were 40 selected studies involving 5696 patients with NCNNLM undergone HR. Pooled data analyses showed that the 3- and 5-year OS were 40% (95% CI 0.35–0.46) and 32% (95% CI 0.29–0.36), whereas the 3- and 5-year DFS were 28% (95% CI 0.21–0.36) and 24% (95% CI 0.20–0.30), respectively. The postoperative morbidity rate was 28%, while the 30-day mortality was 2%. Subgroup analysis on HR for gastric cancer liver metastasis revealed the 3-year and 5-year OS of 39% and 25%, respectively.ConclusionsHR for NCNNLM may achieve satisfactory survival outcome in selected patients with low morbidities and mortalities. However, more concrete evidence from prospective study is warrant in future.     

Increased preoperative levels of plasma fibrinogen and d dimer in patients with renal cell carcinoma is associated with poor survival and adverse tumor characteristics

Background and objectiveThe relationship between renal cell carcinoma (RCC) and coagulation/fibrinolysis system has been described in several studies. The aim of this study was to investigate the role of 4 different coagulation/fibrinolysis factors on the prediction of histopathologic and survival prognosis in patients with RCC.Patients and methodsData from 128 patients who underwent surgical intervention between March 2006 and January 2011 for RCC were evaluated in this prospective study. Blood samples were collected from all patients on the morning of the operation to measure the plasma fibrinogen, d-dimer, coagulation factor VII, and antithrombin 3 levels. The relationships of these factors in the demographic, clinical, and histopathologic outcomes were analyzed using the Student t, Mann-Whitney U, Kruskal-Wallis, and one-way analysis of variance tests. Receiver operating curve analyses were performed to determine the optimal cutoff level for fibrinogen and d dimer, both of which had a strong relation with the clinical and histopathologic parameters. Disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) were assessed using the Kaplan-Meier method. Multivariate Cox regression analyses (forward stepwise logistic regression) were performed to examine the independent prognostic values on survival outcomes.ResultsIncreased plasma fibrinogen and d-dimer levels were associated with tumor size (P = 0.004 and 0.106), nuclear grade (P<0.001 and<0.001), TNM category (P<0.001 and 0.029), and metastasis (P<0.001 and 0.032). Both increased plasma fibrinogen and d-dimer levels predicted decreased DFS (P = 0.027 and 0.04), CSS (P = 0.007 and 0.043), and OS (P = 0.014 and 0.001) rates based on Kaplan-Meier analyses. Furthermore, multivariate analyses demonstrated that fibrinogen independently predicted poor DFS (hazard ratio [HR] = 2.52; 95% CI: 1.04–6.31; P = 0.029) and CSS (HR = 3.89; 95% CI: 1.13–13.40; P = 0.032), whereas d dimer had negative independent prognostic value on OS (HR = 4.01; 95% CI: 1.54–10.50; P = 0.005).ConclusionsIncreased plasma fibrinogen levels accurately predict poor histopathologic and survival outcomes and may be an effective independent prognostic factor in patients with RCC. Moreover, d dimer may serve as a copredictive factor in conjunction with fibrinogen.     

The Usefulness of the Pretreatment Neutrophil/Lymphocyte Ratio as a Predictor of the 5-Year Survival in Stage 1–3 Triple Negative Breast Cancer Patients

BackgroundWe have previously shown that the neutrophil/lymphocyte ratio (NLR) is a predictor of survival among breast cancer patients. The aim of this study was to determine the predictive value of NLR among different nodal and chemotherapy subgroups of triple negative breast cancer (TNBC).MethodsPatients with stage 1–3 TNBC who underwent treatment from 2007 to 2014 and had blood counts prior to treatments were included. Patients were categorized into high (≥2) and low (<2) NLR groups. Primary outcomes were overall survival (OS) and disease-free survival (DFS).ResultsThe average follow-up time was 54 months. The high NLR group had worse OS (HR 2.8, CI 1.3–5.9, p < 0.001) and DFS (HR 2.3, CI 1.2–4.2, p < 0.001) than the low NLR group. After adjusting for confounding variables, high NLR was an independent prognostic factor for both OS (HR 5.5, CI 2.2–13.7, p < 0.0001) and DFS (HR 5.2, CI 2.3–11.6, p < 0.0001). Categorization of TNBC patients by NLR (high vs. low) and nodal status (positive vs. negative) resulted in four groups with significantly different OS and DFS (log rank p < 0.0001). Significant improvements in OS (p < 0.001) and DFS (p < 0.001) were observed for patients who received chemotherapy and had high NLR but not for patients with low NLR (p = 0.65 and p = 0.07, respectively).ConclusionHigh pretreatment NLR is an independent predictor of poor OS and DFS among TNBC patients. Combining NLR and pN provides better risk stratification for TNBC patients. Chemotherapy appears to be beneficial only in patients with high NLR. Larger prospective studies are needed to validate these findings.     

Prognostic Value of Sarcopenia and Albumin in the Surgical Management of Localized Renal Cell Carcinoma

IntroductionA universally accepted model for preoperative surgical risk stratification in localized RCC patients undergoing nephrectomy is currently lacking. Both the evaluation of body composition and nutritional status has demonstrated prognostic value for patients with cancer. This study aims to investigate the potential associations between sarcopenia and hypoalbuminemia and survival outcomes in patients with localized kidney cancer treated with partial or radical nephrectomy.Materials and MethodsWe retrospectively analyzed 473 patients with localized RCC managed with radical and partial nephrectomy. Skeletal muscle index (SMI) was measured from preoperative CT and MRI. Sarcopenic criteria were created using BMI- and sex-stratified thresholds. Relationships between sarcopenia and hypoalbuminemia (Albumin <3.5 g/dL) with overall (OS), recurrence-free (RFS), and cancer-specific survival (CSS) were determined using multivariable and Kaplan-Meier analysis.ResultsOf the 473 patients, 42.5% were sarcopenic and 24.5% had hypoalbuminemia. Sarcopenia was significantly associated with shorter OS (HR=1.51, 95% CI 1.07-2.13), however, was nonsignificant in the RFS (HR = 1.33, 95% CI 0.88-2.03) and CSS (HR=1.66, 95% CI 0.96-2.87) models. Hypoalbuminemia predicted shorter OS (HR=1.76, 95% CI 1.22-2.55), RFS (HR=1.86, 95% CI 1.19-2.89), and CSS (HR=1.82, 95% CI 1.03-3.22). Patients were then stratified into low, medium, and high-risk groups based on the severity of sarcopenia and hypoalbuminemia. Risk groups demonstrated an increasing association with shorter OS (all p<0.05). Reduced RFS was observed in the medium risk-hypoalbuminemia (HR=2.18, 95% CI 1.16-4.09) and high-risk groups (HR=2.42, 95% CI 1.34-4.39). Shorter CSS was observed in the medium risk-hypoalbuminemia (HR=2.31, 95% CI 1.00-5.30) and high-risk groups (HR=2.98, 95% CI 1.34-6.61).ConclusionLocalized RCC patients with combined preoperative sarcopenia and hypoalbuminemia displayed a two to a three-fold reduction in OS, RFS, and CSS after nephrectomy. These data have implications for guiding prognostication and treatment election in localized RCC patients undergoing extirpative surgery.     

Locoregional therapy in de novo metastatic breast cancer: Systemic review and meta-analysis

BackgroundLocoregional therapy (LRT) in de novo metastatic disease is controversial with inconsistent results from randomized control trials (RCTs).MethodsRCTs comparing LRT and systemic therapy to standard therapy alone in de novo metastatic breast cancer were identified. Hazard ratios (HRs) and their associated 95% confidence intervals (CIs) were computed and pooled in a meta-analysis using generic inverse variance. Overall survival (OS) and time to locoregional progression data were extracted for the intention to treat (ITT) population. Data on OS for pre-specified subgroups defined by tumor subtype and by site of metastases were also extracted.ResultsAnalyses included 4 trials comprising 970 patients. LRT included standard surgery to the primary breast tumor in all studies, and adjuvant radiation per standard of care was required in 3 studies. Compared to standard treatment, LRT was not associated with improved OS in the ITT population (HR 0.97, 95% CI 0.72–1.29, p = 0.81). However, LRT was associated with improved time to locoregional progression (HR 0.36, 95% CI 0.14–0.95, p = 0.04). LRT was not associated with improved OS in any tumor subtypes, including hormone receptor positive (HR 0.96, 95% CI 0.65–1.43), triple negative (HR 1.4, 95% CI 0.50–3.91) and human epidermal growth factor receptor 2 positive disease (HR 0.93, 95% CI 0.68–1.28). Additionally, LRT did not improve OS in bone only disease (HR 0.97, 95% CI 0.58–1.62) and in visceral disease (HR = 1.02, 95% CI 0.77–1.35). Our critical appraisal has identified some methodological problems in the design and conduct of the studies included that could affect the meta-analysis result.ConclusionsLRT in de novo metastatic breast cancer is not associated with improved OS. Results are consistent among different breast cancer subgroups. However, this conclusion should be interpreted with caution in view of the limitations identified in meta-analysis.     

Open Versus Thoracoscopic Esophagectomy in Patients with Esophageal Squamous Cell Carcinoma

Background

The impact of minimally invasive esophagectomy on patient prognosis, particularly disease-free survival (DFS), has not been well addressed. We compared the clinical outcomes of open and thoracoscopic esophagectomy in patients with esophageal squamous cell carcinoma (ESCC).

Methods

Sixty-three and 66 patients, nonrandomized, underwent open and thoracoscopic esophagectomies for ESCC between 2008 and 2011 were included. The clinicopathological data were reviewed retrospectively. Perioperative outcome, overall survival (OS), DFS, and the recurrence sites after open and thoracoscopic esophagectomy were compared.

Results

The open and thoracoscopic groups were comparable with regard to the total number of harvested lymph nodes and the percentage patients undergoing R0 resection. Fewer patients in the thoracoscopic group had pneumonia and wound complications. Intensive care unit (ICU) stay also was shorter in the thoracoscopic group. The recurrence pattern was similar in the two groups. In the open and thoracoscopic groups, the 3-year OS rates were 47.6 and 70.9 % (p = 0.031), respectively, and the 3-year DFS rates were 35 and 62.4 % (p = 0.007), respectively. However, the trends in better OS and DFS in the thoracoscopic group were not significant after stratification according to pathologic stage.

Conclusions

The perioperative benefit of thoracoscopic esophagectomy included fewer postoperative complications and shorter ICU stays. Mid-term OS and DFS associated with thoracoscopic techniques are at least equivalent to those associated with open procedures.     

Microsatellite and RAS/RAF Mutational Status as Prognostic Factors in Colorectal Peritoneal Metastases Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

Background

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) leads to prolonged survival for selected patients with colorectal (CRC) peritoneal metastases (PM). This study aimed to analyze the prognostic role of micro-satellite (MS) status and RAS/RAF mutations for patients treated with CRS.

Methods

Data were collected from 13 Italian centers with PM expertise within a collaborative group of the Italian Society of Surgical Oncology. Clinical and pathologic variables and KRAS/NRAS/BRAF mutational and MS status were correlated with overall survival (OS) and disease-free survival (DFS).

Results

The study enrolled 437 patients treated with CRS-HIPEC. The median OS was 42.3 months [95% confidence interval (CI), 33.4–51.2 months], and the median DFS was 13.6 months (95% CI, 12.3–14.9 months). The local (peritoneal) DFS was 20.5 months (95% CI, 16.4–24.6 months). In addition to the known clinical factors, KRAS mutations (p = 0.005), BRAF mutations (p = 0.01), and MS status (p = 0.04) were related to survival. The KRAS- and BRAF-mutated patients had a shorter survival than the wild-type (WT) patients (5-year OS, 29.4% and 26.8% vs 51.5%, respectively). The patients with micro-satellite instability (MSI) had a longer survival than the patients with micro-satellite stability (MSS) (5-year OS, 58.3% vs 36.7%). The MSI/WT patients had the best prognosis. The MSS/WT and MSI/mutated patients had similar survivals, whereas the MSS/mutated patients showed the worst prognosis (5-year OS, 70.6%, 48.1%, 23.4%; p = 0.0001). In the multivariable analysis, OS was related to the Peritoneal Cancer Index [hazard ratio (HR), 1.05 per point], completeness of cytoreduction (CC) score (HR, 2.8), N status (HR, 1.6), signet-ring (HR, 2.4), MSI/WT (HR, 0.5), and MSS/WT-MSI/mutation (HR, 0.4). Similar results were obtained for DFS.

Conclusion

For patients affected by CRC-PM who are eligible for CRS, clinical and pathologic criteria need to be integrated with molecular features (KRAS/BRAF mutation). Micro-satellite status should be strongly considered because MSI confers a survival advantage over MSS, even for mutated patients.

     

Operative outcome of laparoscopic colorectal cancer surgery in a regional hospital in a developing country: A propensity score-matched comparative analysis

ObjectiveLaparoscopic surgery is an alternative procedure for colorectal cancers. However, high-level supporting evidence has been derived from high-volume centers in developed countries. During the early phase of applying the laparoscopic approach, we evaluated the procedure’s short-term outcomes in our regional middle-volume hospital in a developing country.MethodsWe retrospectively analyzed data for a cohort of 223 colorectal cancer patients who underwent elective surgery from October 2017 to September 2019. We compared 165 patients undergoing open surgery (OS group) with 58 undergoing laparoscopic surgery (LS group) using a propensity score-matched analysis.ResultsAfter matching, each group contained 58 patients for evaluating outcomes. The LS group had more harvested mesenteric lymph nodes (5.0 nodes, 95% confidence interval (CI): 1.8–8.1; p-value: <0.01) with comparable blood loss (p-value: 0.54) and margin status (p-value: 0.66). However, LS was more time-consuming (68.8 min longer; 95% CI: 53.0–84.7; p-value: <0.01). Morbidity and mortality rates were equivalent (odds ratio (OR): 1.3, 95% CI: 0.25–2.73, p-value: 0.74, and OR: 2, 95% CI: 0.18–22.1, p-value: 0.57, respectively). The LS group experienced fewer days to begin normal eating (?0.5 days, 95% CI: ?0.9 to ?0.1, p-value: 0.04) and shorter hospital stay (?1.5 days, 95% CI: ?2.7 to ?0.4, p-value: <0.01). The conversion rate was 3.5%.ConclusionThe laparoscopic approach was applicable even in a regional middle-volume hospital in a developing country. However, longer surgical time was a drawback.     

Low ERCC1 expression is associated with prolonged survival in patients with bladder cancer receiving platinum-based neoadjuvant chemotherapy

PurposeExcision repair cross-complementation group 1 enzyme (ERCC1) plays a key role in the removal of platinum induced DNA adducts and cisplatin resistance. Prognostic role of ERCC1 expression in the neoadjuvant setting in bladder cancer has not been reported before. We evaluated the prognostic role of ERCC1 expression in bladder cancer receiving platinum-based neoadjuvant chemotherapy.Materials and methodsThirty-eight patients with muscle invasive bladder cancer who received neoadjuvant platinum-based chemotherapy were included. Clinical and histopathologic parameters along with immunohistochemical ERCC1 staining were examined and correlated with response rates and survival.ResultsPathologic complete response rates were similar between patients with low and high ERCC1 expression. Median disease-free survival (DFS) was 9.3 vs. 20.5 months (P = 0.186) and median overall survival (OS) was 9.3 vs. 26.7 months (P = 0.058) in patients with high ERCC1 expression compared with those with low expression, respectively. In multivariate Cox regression analysis: pathological complete response (pCR) after chemotherapy (hazard ratio (HR) 0.1, 95% CI 0.012–0.842, P = 0.034) and high ERCC1 expression (HR 3.7, 95% CI 1.2–11.2, P = 0.019) were significantly associated with DFS. Patient age (>60 vs. ≤60 years) (HR 3.4, 95% CI 1.2–9.4, P = 0.018), the presence of pCR (HR 0.11, 95% CI 0.014–0.981, P = 0.048) and high ERCC expression (HR 6.1, 95 CI 1.9–19.9, P = 0.002) were significantly associated with OS.ConclusionsOur results showed that high ERCC1 expression was independently associated with shorter disease-free and overall survival in patients with bladder cancer who received neoadjuvant platinum-based chemotherapy. ERCC1 may represent a potential predictive marker for platinum-based treatment in bladder cancer.