The impact of nutritional risk factors and sarcopenia on survival in patients treated with pelvic exenteration for recurrent gynaecological malignancy: a retrospective cohort study.

PURPOSE: The aim of the present study is to investigate the prognostic significance of nutritional risk factors and sarcopenia on the outcome of patients with recurrent gynaecological malignancies treated by pelvic exenteration. METHODS: We retrospectively evaluated muscle body composite measurements based on pre-operative CT scans, nutritional risk factors as assessed by a validated pre-operative questionnaire, and clinical-pathological parameters in 65 consecutive patients with recurrent gynaecological malignancies, excluding ovarian cancer, treated by pelvic exenteration at the Royal Marsden Hospital London. Predictive value for postoperative morbidity was investigated by logistic regression analyses. Relevant parameters were included in uni- and multivariate survival analyses. RESULTS: We found only (1) low muscle attenuation (MA)-an established factor for muscle depletion-and (2) moderate risk for malnutrition to be independently associated with shorter overall survival (p = 0.006 and p = 0.008, respectively). MA was significantly lower in overweight and obese patients (p = 0.04). Muscle body composite measurements were not predictive for post-operative morbidity. CONCLUSION: The study suggests that pre-operative low MA and moderate risk for malnutrition are associated with shorter survival in patients with recurrent gynaecological malignancies treated with pelvic exenteration. Further studies are needed to validate these findings in larger cohorts.

False negative rate at 18F-FDG PET/CT in para-aortic lymphnode involvement in patients with locally advanced cervical cancer: impact of PET technology.

BACKGROUND: The identification of factors responsible for false negative (FN) rate at 18F- Fluorodeoxyglucose (FDG) Positron Emission Tomography /Computed Tomography (PET/CT) in para-aortic (PA) lymph nodes in the presurgical staging of patients with locally advanced cervical cancer (LACC) is challenging. The aim of this study was to evaluate the impact of PET/CT technology. METHODS: A total of 240 consecutive patients with LACC (International Federation of Gynecology and Obstetrics, FIGO, stage IB2-IVA) and negative Magnetic Resonance Imaging (MRI) and/or Computed Tomography (CT) and negative 18F-FDG PET/CT in the PA region, undergoing laparoscopic PA lymphadenectomy before chemoradiotherapy were included. The FN rate in patients studied with Time of flight (TOF) PET/CT (TOF PET) or non-Time of flight PET/CT (no-TOF PET) technology was retrospectively compared. RESULTS: Patients presented with FIGO stage IB (n = 78), stage IIA-B (n = 134), stage III (n = 18) and stage IVa (n = 10), squamous cell carcinoma (n = 191) and adenocarcinoma (n = 49). 141/240 patients were evaluated with no-TOF PET/CT and 99/240 with TOF PET/CT. Twenty-two patients (9%) had PA nodal involvement at histological analysis and considered PET/CT FN findings. The FN rate was 8.5% for no-TOF PET and 10% for TOF PET subgroup respectively (p = 0.98). Ninety patients (38%) presented with pelvic node uptakes at PET/CT. The FN rate in the PA region was 18% (16/90) and 4% (6/150) in patients with and without pelvic node involvement at PET/CT respectively (19 vs 3% for no-TOF PET and 17 vs 5% for TOF PET subgroup). CONCLUSIONS: In LACC, FN rate in PA lymph nodes detection is a clinical issue even for modern PET/CT, especially in patients with pelvic uptake. Surgical lymphadenectomy should be performed in case of negative PET/CT at PA level in these patients, while it could be discussed in the absence of pelvic uptake.

Impact of frailty on the management of patients with gynecological cancer aged 80 years and older.

PURPOSE: To assess the impact of frailty on compliance of standard therapy, complication, rate and survival in patients with gynecological malignancy aged 80 years and older. METHODS: In total, 83 women with gynecological malignancy (vulva, endometrial, ovarian or cervical cancer) who underwent primary treatment between 2007 and 2017 were retrospectively analyzed. Frailty index was calculated and its association with compliance of standard treatment, peri- and postoperative mortality and morbidity, and survival was evaluated. RESULTS: Frailty was observed in 24.1% of cases. Both frail and non-frail patients were able to receive standard therapy in most cases - 75.0% and 85.7%, respectively (p = 0.27). Frail patients did not show an increased postoperative complication rate. Frail patients had shorter 3 years overall survival rates (28%) when compared to non-frail patients (55%) (p = 0.02). In multivariable analysis high frailty index (Hazard Ratio [HR] 12.15 [1.39-106.05], p = 0.02) and advanced tumor stage (HR 1.33 [1.00-1.76], p = 0.05) were associated with poor overall survival, but not age, histologic grading, performance status, and compliance of standard therapy. CONCLUSION: Majority of patients was able to receive standard therapy, as suggested by the tumor board, irrespective of age and frailty. Nonetheless, frailty is a common finding in patients with gynecological malignancy aged 80 years and older. Frail patients show shorter progression-free, and overall survival within this cohort.

Molecular Guided Treatments in Gynecologic Oncology: Analysis of a Real-World Precision Cancer Medicine Platform.

INTRODUCTION: Advanced gynecologic cancers have a poor prognosis and constitute a major challenge for adequate treatment strategies. By analyzing and targeting molecular alterations, molecular guided treatments may be a viable option for the treatment of advanced gynecologic cancers. PATIENTS AND METHODS: In this single-center, real-world retrospective analysis of our platform for precision cancer medicine (PCM), we describe the molecular profiling of 72 patients diagnosed with different types of advanced gynecologic malignancies. Tumor samples of the patients were examined by next-generation sequencing panel and immunohistochemistry (IHC). RESULTS: In total, we identified 209 genetic aberrations in 72 patients. The ten most frequent alterations were TP53 (n = 42, 20%), KRAS (n = 14, 6.6%), PIK3CA (n = 11, 5.2%), PIK3R1 (n = 9, 4.3%), ATR (n = 8, 3.8%), PTEN (n = 8, 3.8%), BRCA1 (n = 6, 2.8%), NF1 (n = 4, 1.9%), NOTCH1 (n = 4, 1.9%), and POLE (n = 4, 1.9%), which account for more than half of all molecular alterations (52.6%). In 21 (29.1%) patients only one mutation could be detected, and 44 (61.1%) patients had more than one mutation. No molecular alterations were detected in seven (9.7%) patients. IHC detected expression of phosphorylated mammalian target of rapamycin and epidermal growth factor receptor in 58 (80.6%) and 53 (73.6%) patients, respectively. In over two thirds (n = 49, 68.1%), a targeted therapy was suggested, based on the identified genetic aberrations. The most frequently recommended specific treatment was the combination of everolimus with exemestane (n = 18, 25 %). CONCLUSION: Based on our observations, it seems that PCM might be a feasible approach for advanced gynecologic cancers with limited treatment options. IMPLICATIONS FOR PRACTICE: Nowadays molecular profiling of advanced gynecologic malignancies is feasible in the clinical routine. A molecular portrait should be done for every patient with an advanced therapy-refractory gynecologic malignancy to offer molecular-based treatment concepts.

Prognostic value of T1 substaging on oncological outcomes in patients with non-muscle-invasive bladder urothelial carcinoma: a systematic literature review and meta-analysis.

PURPOSE: To evaluate the prognostic value of substaging on oncological outcomes in patients with T (or pT1) urothelial carcinoma of the bladder. METHODS: A literature search using PubMed, Scopus, Web of Science, and Cochrane Library was conducted on March 2019 to identify relevant studies according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. The pooled disease recurrence (DR) and disease progression (DP) rate in T1(or pT1) patients were calculated using a fixed or random effects model. RESULTS: Overall 36 studies published between 1994 and 2018 including a total of 6781 bladder cancer patients with T1(or pT1) stage were selected for the systematic review and meta-analysis. Twenty-nine studies reported significant association between tumor infiltration depth or muscularis mucosa (MM) invasion and oncological outcomes. Totally 12 studies were included in the meta-analysis. MM invasion (T1a/b/c [or pT1a/b/c] or T1a/b [or pT1a/b] substaging system) was associated with DR (pooled HR: 1.23, 95%CI: 1.01-1.49) and DP (pooled HR: 2.61, 95%CI: 1.61-4.23). Tumor infiltration depth (T1 m/e [or pT1 m/e] substaging system) was also associated with DR (pooled HR: 1.49, 95%CI: 1.11-2.00) and DP (pooled HR: 3.29, 95%CI: 2.39-4.51). CONCLUSIONS: T1(or pT1) substaging in patients with bladder cancer is of prognostic value as it is associated with oncologic outcomes. Inclusion of this factors into the clinical decision-making process of this heterogeneous tumor may improve outcomes, while avoiding over- and under-treatment for T1(or pT1) bladder cancer.

The value of pretreatment serum butyrylcholinesterase level as a novel prognostic biomarker in patients with cervical cancer treated with primary (chemo-)radiation therapy.

BACKGROUND: Deficiency in butyrylcholinesterase (BChE), a condition commonly noticed in liver damage, inflammation, and malnutrition, has previously been associated with impaired prognosis in different malignancies. The aim of the present study was to investigate the value of pretreatment serum BChE levels as a prognostic biomarker in patients with cervical cancer treated with primary (chemotherapy-[chemo-])radiation therapy. METHODS: We retrospectively evaluated data of a consecutive series of patients with cervical cancer treated with primary (chemo-)radiation therapy between 1998 and 2015. Pretreatment serum BChE levels were correlated with clinico-pathological parameters and response to treatment. Uni- and multivariate survival analyses were performed to assess the association between decreased serum BChE levels and progression-free (PFS), cancer-specific (CSS), and overall survival (OS). RESULTS: A total of 356 patients were eligible for inclusion into the present study. The median (IQR) pretreatment serum BChE level was 6180 (4990-7710) IU/l. Lower serum BChE levels were associated with lower BMI (p < 0.001), advanced tumor stage (p = 0.04), poor treatment response (p = 0.002), the occurrence of disease recurrence (p = 0.003), and the risk of death (p < 0.001). In uni- and multivariate analyses, low pretreatment serum BChE levels were independently associated with shorter PFS (HR 1.8 [1.2-2.6]; p = 0.002), CSS (HR 2.2 [1.4-3.5], p < 0.001), and OS (HR 2.0 [1.4-2.9]; p < 0.001). CONCLUSIONS: Low pretreatment serum BChE levels are associated with advanced tumor stage and poor response to treatment, and serve as an independent prognostic biomarker for shorter PFS, CSS, and OS in patients with cervical cancer treated with primary (chemo-)radiation therapy.

Pre-operative hypoalbuminemia is associated with complication rate and overall survival in patients with vulvar cancer undergoing surgery.

OBJECTIVE: Hypoalbuminemia, a known marker for malnutrition, has been associated with an increased risk for perioperative morbidity and poor prognosis in patients with solid tumors. The aim of this study was to investigate the prognostic and predictive value of pre-treatment serum albumin levels for survival and postoperative complications in patients with vulvar cancer undergoing surgery. METHODS: Within in this retrospective study, we assessed data of 103 consecutive patients with vulvar cancer undergoing primary surgery into this study. Pre-treatment serum albumin levels were correlated with clinico-pathological parameters and complications. We performed univariate log-rank test and multivariable Cox regression models to evaluate the association between pre-treatment serum albumin and survival. RESULTS: We found hypoalbuminemia (< 35 mg/dl) in 9 of 103 (8.7%) patients. No difference in tumor characteristics was observed between patients with hypoalbuminemia and normal serum albumin levels. Difference in postoperative complications (55.6% and 37.8% of patients with hypoalbuminemia and normal serum albumin levels, respectively) was not statistically significant (p = 0.345). Shorter overall survival (OS) was observed in patients with hypoalbuminemia (5-year OS rate 17.1%) when compared to patients with normal serum albumin levels (5-year OS rate 58.6%, p = 0.004). In multivariable analysis, age (p = 0.017), FIGO stage (p = 0.011) and serum albumin levels (p = 0.013) were independently associated with OS. CONCLUSION: Pre-treatment hypoalbuminemia is an independent prognostic biomarker for OS in patients with vulvar cancer. We did not find an association between pre-treatment hypoalbuminemia and a higher risk for postoperative complications.

Factors associated with post-relapse survival in patients with recurrent cervical cancer: the value of the inflammation-based Glasgow Prognostic Score.

PURPOSE: The aim of the present study was to assess the value of the Glasgow Prognostic Score (GPS) as a prognostic tool for predicting post-relapse survival (PRS) in patients with recurrent cervical cancer. METHODS: We retrospectively evaluated the data of 116 patients with recurrent cervical cancer in whom serologic biomarkers had been assessed at the time of relapse. The GPS was calculated as follows: patients with elevated serum C-reactive protein levels and hypoalbuminemia were allocated a score of 2, and those with 1 or no abnormal value were allocated a score of 1 and 0, respectively. To assess the association between factors including the GPS and PRS, we performed uni- and multivariate survival analyzes. RESULTS: After a median follow-up of 20.9 months from recurrence, a 5-year PRS rate of 25% (SE 4.7%) was observed. Only in 29.8% of the patients, recurrence was limited to the pelvis. In uni- and multivariate survival analyzes, the GPS [HR 1.6 (95% CI 0.9-2.4), p = 0.01], a history of radiation therapy as part of initial treatment [HR 2.7 (95% CI 1.1-6.9), p = 0.03], and the presence of peritoneal carcinomatosis or multiple sites of relapse [HR 4.2 (95% CI 1.9-9.3), p < 0.001] were associated with shorter PRS. The GPS correlated with higher squamous cell carcinoma antigen levels (p = 0.001), shorter median PRS (p = 0.009), and less intensive treatment for relapse (p = 0.02). CONCLUSIONS: A higher GPS at the time of relapse, a history of radiation therapy, and the presence of peritoneal carcinomatosis or multiple sites of relapse are independently associated with shorter PRS in patients with recurrent cervical cancer.

AB0 blood groups and rhesus factor expression as prognostic parameters in patients with epithelial ovarian cancer - a retrospective multi-centre study.

BACKGROUND: AB0 blood groups and Rhesus factor expression have been associated with carcinogenesis, response to treatment and tumor progression in several malignancies. The aim of the present study was to test the hypothesis that AB0 blood groups and Rhesus factor expression are associated with clinical outcome in patients with epithelial ovarian cancer (EOC). METHODS: AB0 blood groups and Rhesus factor expression were evaluated in a retrospective multicenter study including 518 patients with EOC. Their association with patients' survival was assessed using univariate and multivariable analyses. RESULTS: Neither AB0 blood groups nor Rhesus factor expression were associated with clinico-pathological parameters, recurrence-free, cancer-specific, or overall survival. In a subgroup of patients with high-grade serous adenocarcinoma, however, blood groups B and AB were associated with a better 5-year cancer-specific survival rate compared to blood groups A and 0 (60.3 ± 8.6% vs. 43.8 ± 3.6%, p = 0.04). Yet, this was not significant in multivariable analysis. CONCLUSIONS: AB0 blood groups and Rhesus factor expression are both neither associated with features of biologically aggressive disease nor clinical outcome in patients with EOC. Further investigation of the role of the blood group B antigen on cancer-specific survival in the subgroup of high-grade serous should be considered.

A phase I, single-arm, open-label, dose escalation study of intraperitoneal cisplatin and doxorubicin in patients with recurrent ovarian cancer and peritoneal carcinomatosis.

OBJECTIVE: We performed a phase I, single-arm, non-randomized, open-label, dose-escalation trial to determine the dose-limiting toxicity of intraperitoneal cisplatin and doxorubicin applied as pressurized intraperitoneal aerosol chemotherapy (PIPAC) in women with recurrent ovarian cancer. METHODS: We used a standard 3 + 3 dose-escalation design with doxorubicin 1.5 mg/m2, cisplatin 7.5 mg/m2 q 4 to 6 weeks for 3 cycles and subsequent dose escalation steps (20% increment per step) in patients with recurrent ovarian cancer and peritoneal carcinomatosis. Toxicity and clinical efficacy were monitored. The primary endpoint was the maximum-tolerable dose. Secondary endpoints included histologic tumor regression and serum parameters. RESULTS: 15 evaluable patients (3, 7, and 5 in cohorts 1, 2, and 3, respectively) on average received 2.3 PIPAC cycles. No dose limiting toxicities were found. Adverse side effects were 1 grade 3 event (colon perforation) and 85 grade 1/2 events including fatigue (n = 19), abdominal pain (n = 18), nausea/vomiting (n = 14), sleep disorder (n = 8), diarrhea (n = 5), and fever (n = 2). Liver and renal toxicity was not observed in any of the 3 cohorts (AST 19.1 ±â€¯3.2, 25.8 ±â€¯6.5, and 22.1 ±â€¯4.5 IU/L, respectively; ALT 14.7 ±â€¯3.5, 18.5 ±â€¯5.6, and 23.3 ±â€¯13.0 IU/L, respectively; GGT 45.7 ±â€¯35.1, 25.2 ±â€¯10.3, and 43.9 ±â€¯26.4 IU/L, respectively; serum creatinine 1.06 ±â€¯0.23, 0.80 ±â€¯0.17, and 0.89 ±â€¯0.35 mg/dL, respectively). No systemic hematologic toxicity, alopecia, or neurotoxicity was noted. The maximum tolerable dose was not reached. Histologic tumor regression was observed in 7/11 (64%) patients who underwent ≥2 PIPAC cycles. CONCLUSIONS: PIPAC with cisplatin and doxorubicin may be safely used at an intraperitoneal dose of 10.5 mg/m2 and 2.1 mg/m2, respectively. Systemic toxicity of this therapy is low.

Accuracy and prognostic value of variant histology and lymphovascular invasion at transurethral resection of bladder.

OBJECTIVES: To evaluate the concordance rate of lymphovascular invasion (LVI) and variant histology (VH) of transurethral resection (TUR) with radical cystectomy (RC) specimens. Furthermore, to evaluate the value of LVI and VH at TUR for predicting non-organ confined (NOC) disease, lymph node metastasis, and survival outcomes. PATIENTS AND METHODS: Two hundred and sixty-eight patients who underwent TUR and subsequent RC were reviewed. Logistic regression analyses were performed to evaluate the association of LVI and VH with NOC and lymph node metastasis at RC. Cox regression analyses were used to estimate recurrence-free survival (RFS) and cancer-specific survival (CSS). RESULTS: LVI and VH were detected in 13.8 and 11.2% of TUR specimens, and in 30.2 and 25.4% of RC specimens, respectively. The concordance rate between LVI and VH at TUR and subsequent RC was 69.8 and 83.6%, respectively. They were both associated with adverse pathological features such as lymph node metastasis and advanced stage. TUR LVI and VH were both independently associated with lymph node metastasis and TUR VH was independently associated with NOC. On univariable Cox regression analyses, TUR LVI was associated with RFS and CSS while TUR VH was only associated with RFS. Only TUR LVI was independently associated with RFS. CONCLUSION: Detection of LVI is missed in a third of TUR specimens while VH seems more accurately identified. TUR LVI and VH are associated with more advanced disease and LVI predicts disease recurrence. Assessment and reporting of LVI and VH on TUR specimen are important for risk stratification and decision-making.

Preoperative C-reactive protein serum levels as a predictive diagnostic marker in patients with adnexal masses.

OBJECTIVE: To evaluate C-reactive protein (CRP) serum levels as a preoperative predictive marker for ovarian cancer in patients with adnexal masses. METHODS: CRP serum levels of 1843 adnexal masses and subsequent surgery were investigated (patients with benign ovarian tumors: n=1423; borderline tumor of the ovary [BTO]: n=83; EOC: n=337). Test characteristics and predictive values of CRP serum levels were investigated by univariate analysis and multivariate binary logistic regression models. RESULTS: Median (interquartile range) serum CRP levels in patients with benign ovarian tumors, BTO, and EOC were 0.4 (0.1-0.6)mg/dL, 0.5 (0.2-0.9)mg/dL, and 1.6 (0.5-5.4)mg/dL, respectively (p<0.001). Sensitivity and specificity of the combination of CRP and CA-125 was 80.1% and 90.8%, negative predictive value (NPV) and positive predictive value (PPV) was 92.2% and 76.9%, respectively. In univariate and multivariate analysis, CRP serum levels were independently associated with presence of BTO and EOC (HR 6.7 [5.2-8.5], p<0.001 and HR 2.2 [1.4-3.3], p<0.001). The combination of CRP and CA-125 serum levels resulted in a number needed to treat of 2.11 to detect one case of EOC or BTO. CONCLUSION: CRP serum levels independently predicted the presence of BTO and EOC in patients with suspicious adnexal masses. CRP serum levels seem to be of additional value to CA-125 in the preoperative differential diagnosis of adnexal masses and might be particularly in combination with CA-125 clinically useful.

Plasma fibrinogen levels in patients with benign and malignant ovarian tumors.

OBJECTIVE: Plasma fibrinogen is a key acute phase protein and known to be elevated in ovarian cancer. We aimed to investigate the association between plasma fibrinogen and malignant and benign ovarian tumors. METHODS: In a retrospective, single-center study, we evaluated preoperative plasma fibrinogen levels in 471 patients with benign and in 224 patients with malignant (borderline ovarian tumor [BOT]: n=36, epithelial ovarian cancer [EOC]: n=188) ovarian tumors. The association between preoperative plasma fibrinogen levels and clinico-pathological parameters was investigated. A multivariate logistic regression model was performed to identify an independent association. RESULTS: Mean (standard deviation) preoperative plasma fibrinogen levels in patients with benign ovarian tumors, BOT, and invasive ovarian cancers were 346.7 (99.7), 372.8 (114), and 472.6 (148.4) mg/dL, respectively (p<0.001). Within the EOC cohort, patients with advanced stage disease had higher plasma fibrinogen levels (485.5 [151.3] mg/dL) than patients with early stage disease (430.9 [130.3] mg/dL; p=0.03). In a multivariate model plasma fibrinogen was identified to be independently associated with the presence of BOT and EOC. In the subgroup of patients <50 years, plasma fibrinogen levels remained independently associated with malignant ovarian tumors in CA 125 positive and negative patients. CONCLUSION: Plasma fibrinogen levels are independently associated with malignant ovarian tumors. Plasma fibrinogen levels showed an independent association with malignant ovarian tumors in the subgroup of patients <50 years, in whom differential diagnosis of ovarian tumors is particularly challenging.

Sorafenib in advanced, heavily pretreated patients with soft tissue sarcomas.

Therapeutic options for patients with advanced pretreated soft tissue sarcomas are limited. However, in this setting, sorafenib has shown promising results. We reviewed the data of 33 patients with soft tissue sarcoma treated with sorafenib within a named patient program in Austria. Twelve physicians from eight different hospitals provided records for the analysis of data. Among the 33 patients, the predominant histological subtype of sarcoma was leiomyosarcoma (n=18, 55%). Other subtypes were represented by only one or two cases. Fifteen patients presented with metastases at the time of diagnosis. Another 17 patients developed metastases later in the course of the disease (data on one patient are missing). Most of the 33 patients had undergone resection of the primary (n=29, 88%) and half of the patients had received radiotherapy (n=17, 52%). Chemotherapy for metastatic disease had been administered to 30 patients (91%). The majority had received two or more regimens of chemotherapy (n=25, 76%) before sorafenib treatment. The use of sorafenib resulted in a median time to treatment failure of 92 days in patients with leiomyosarcoma and 45 days in patients with other histological subtypes. One-third of the patients derived benefits from treatment: four patients were documented with partial response and six with stabilized disease. In terms of treatment-related toxicity, skin problems of various degrees and gastrointestinal disturbances were frequently reported. In this retrospective analysis of heavily pretreated patients with advanced soft tissue sarcomas, sorafenib was associated with some antitumor activity and an acceptable toxicity profile.

External validation of a nomogram predicting overall survival of patients diagnosed with endometrial cancer.

OBJECTIVES: Nomograms are predictive models that provide the overall probability of a specific outcome. Nomograms have shown better individual discrimination than currently used staging systems in numerous tumor entities. Recently, a nomogram for predicting overall survival (OS) in women with endometrial cancer was introduced by Memorial Sloan-Kettering Cancer Center (MSKCC). The aim of this study was to test the validity of the MSKCC endometrial cancer nomogram using an independent, external patient cohort. METHODS: The MSKCC nomogram is based on five readily available clinical characteristics. A multi-institutional endometrial cancer database was used to test the nomogram's validity. All consecutive patients treated for endometrial cancer between December 1995 and May 2011 and who had all nomogram variables documented were identified for analysis. RESULTS: Seven hundred sixty-five eligible patients were identified and used for external validation analysis. In the Austrian patient cohort, median OS was 134 months, and 3-year and 5-year OS rates were 83.8% (95% CI, 80.6-86.5%) and 77.2% (95% CI, 43.5-80.5%), respectively. The nomogram concordance index was 0.71 (SE=0.017; 95% CI, 0.68-0.74). The correspondence between the actual OS and the nomogram predictions suggests a good calibration of the nomogram in the validation cohort. CONCLUSION: The MSKCC endometrial cancer nomogram was externally validated and was shown to be generalizable to a new and independent patient population. The nomogram provides a more individualized and accurate estimation of OS for patients diagnosed with endometrial cancer following primary therapy. The nomogram can be used for counseling patients more accurately and for better stratifying patients for clinical trials.

Prostate-Specific Membrane Antigen (PSMA) Expression in Tumor-Associated Neovasculature Is an Independent Prognostic Marker in Patients with Ovarian Cancer.

Prostate-specific membrane antigen (PSMA) is present in the tumor-associated neovasculature of many cancer types. Current data in ovarian cancer are limited and controversial; thus, the aim of this study was to investigate PSMA expression in a larger and homogenous patient cohort. This might lead to further studies investigating the use of imaging and therapeutic modalities targeting PSMA. Eighty patients with advanced stage high-grade serous ovarian cancers were included. Using immunohistochemistry, PSMA and CD31, a marker for endothelial cells, were examined in whole tissue sections. Percentage and intensity of PSMA expression were determined in the neovasculature. Expression levels were correlated with clinicopathological parameters and survival. Low (≤10%), medium (20-80%), and high (≥90%) PSMA expression was found in 14, 46, and 20 ovarian cancer samples, respectively. PSMA expression was confined to tumor-associated neovasculature and significantly correlated with progression-free (HR 2.24, 95% CI 1.32-3.82, p = 0.003) and overall survival (HR 2.73, 95% CI 1.41-5.29, p = 0.003) in multivariate models, considering age, FIGO stage, and residual disease. This is the first study showing a clinical relevance for PSMA in patients with ovarian cancer. PSMA was detected in the vast majority of cancer samples and showed an impact on survival.

The inflammation-based Glasgow Prognostic Score predicts survival in patients with cervical cancer.

OBJECTIVES: The Glasgow Prognostic Score (GPS) is known to reflect the degree of tumor-associated cachexia and inflammation and is associated with survival in various malignancies. We investigated the value of the GPS in patients with cervical cancer. METHODS: We included 244 consecutive patients with cervical cancer in our study. The pretherapeutic GPS was calculated as follows: patients with elevated C-reactive protein serum levels (>10 mg/L) and hypoalbuminemia (<35 g/L) were allocated a score of 2, and patients with 1 or no abnormal value were allocated a score of 1 or 0, respectively. The association between GPS and survival was evaluated by univariate log-rank tests and multivariate Cox regression models. The GPS was correlated with clinicopathologic parameters as shown by performing chi2 tests. RESULTS: In univariate analyses, GPS (P < 0.001, P < 0.001), International Federation of Gynecology and Obstetrics (FIGO) stage (P < 0.001, P < 0.001), and lymph node involvement (P < 0.001, P < 0.001), but not patients' age (P = 0.2, P = 0.07), histological grade (P = 0.08, P = 0.1), and histological type (P = 0.8, P = 0.9), were associated with disease-free and overall survival, respectively. In a multivariate analysis GPS (P = 0.03, P = 0.04), FIGO stage (P = 0.006, P = 0.006), and lymph node involvement (P = 0.003, P = 0.002), but not patients' age (P = 0.5, P = 0.5), histological grade (P = 0.7, P = 0.6), and histological type (P = 0.4, P = 0.6) were associated with disease-free and overall survival, respectively. The GPS was associated with FIGO stage (P < 0.001) and histological grade (P = 0.02). CONCLUSIONS: The GPS can be used as an inflammation-based predictor for survival in patients with cervical cancer.

The prognostic value of the urokinase-plasminogen activator system (uPA) in bladder cancer patients treated with radical cystectomy (RC).

PURPOSE: Urokinase-plasminogen activator (uPA), its receptor (uPAR), and the plasmin-activator inhibitor type 1 (PAI-1) have been associated with oncologic outcomes in various malignancies and could help identify bladder cancer (BC) patients treated with radical cystectomy (RC) who are likely to benefit from intensification of therapy to prevent disease progression. Our aim was to assess the value of uPA, uPAR, and PAI-1 for prognosticating survival outcomes of patients treated with RC for BC. MATERIALS AND METHODS: Tumor specimens from 272 consecutive patients treated with RC for advanced BC were assessed with immunohistochemical staining for uPA, uPAR, and PAI-1. Overexpression was assessed by pathological image analysis. Kaplan-Meier estimates and multivariable Cox-regression were used to analyze survival. Harrell's C-index was used to assess for clinical impact of the uPA system. RESULTS: uPA, uPAR, and PAI-1 were overexpressed in 48.2%, 51.1%, and 52.2% of patients, respectively. uPA overexpression was associated with lymphovascular invasion (P = 0.034) and nodal status (P = 0.013); PAI-1 overexpression was associated with primary muscle-invasive BC (P = 0.015) and lymphovascular invasion (P = 0.024). uPA, uPAR, and the number of overexpressed markers were all 3 significantly associated with shorter overall recurrence-free-, distant recurrence-free-, and cancer-specific survival. In multivariable analyses, uPA overexpression remained associated with shorter recurrence-free survival (hazard ratio [HR] = 1.79; P = 0.036) in the entire cohort, in patients without lymph node metastasis (HR = 1.98; P = 0.018) and those with nonorgan-confined disease (HR = 1.98; P = 0.022). uPAR overexpression was associated with shorter recurrence-free survival in patients without lymph node metastasis (HR = 2.01; P = 0.021) and those with organ-confined disease (HR = 4.11; P = 0.037). CONCLUSION: Members of the uPA system are associated with features of biologically aggressive BC and oncologic outcomes. However, their value beyond currently available information remains limited.

Impact of Gender on Chemotherapeutic Response and Oncologic Outcomes in Patients Treated With Radical Cystectomy and Perioperative Chemotherapy for Bladder Cancer: A Systematic Review and Meta-Analysis.

Female patients with bladder cancer (BCa) have had more advanced disease than their male counterparts at diagnosis and have experienced worse oncologic outcomes. However, the effect of gender on the chemotherapeutic response and oncologic outcomes after radical cystectomy (RC) and perioperative chemotherapy remains to be elucidated. We performed a systematic literature search to identify eligible studies that had investigated the effect of gender on the chemotherapeutic response and oncologic outcomes after RC and perioperative chemotherapy. We identified 15 studies reported from 2008 to 2019. For the patients who had received neoadjuvant chemotherapy (NAC), female gender was not associated with a complete response (pooled odds ratio [OR], 0.94; 95% confidence interval [CI], 0.69-1.26) nor a complete or partial response (pooled OR, 0.96; 95% CI, 0.73-1.27). In addition, women experienced had less upstaging (pooled OR, 0.3; 95% CI, 0.14-0.68) at RC compared with their male counterparts. Moreover, female patients who had undergone RC and NAC were likely to have better disease recurrence and cancer-specific mortality rates than were the male patients (pooled hazard ratio [HR], 0.66 and 95% CI, 0.44-0.98; and pooled HR, 0.49 and 95% CI, 0.29-0.81, respectively). For the patients who had undergone adjuvant chemotherapy, female gender was not associated with overall mortality (pooled HR, 1.15; 95% CI, 0.7-1.89), disease recurrence (pooled HR, 0.95; 95% CI, 0.74-1.23), or cancer-specific mortality (pooled HR, 1.07; 95% CI, 0.81-1.43). Female patients with BCa seem to benefit more from NAC than do their male counterparts. This potential differential sensitivity of female BCa to cisplatin-based combination chemotherapy might help close the gender gap in BCa, suggesting that gender could be a biomarker to help select the best systemic therapy for patients with advanced BCa.

Plasma fibrinogen levels and prognosis in patients with ovarian cancer: a multicenter study.

INTRODUCTION: To evaluate pretherapeutic plasma fibrinogen levels as a prognostic parameter in patients with epithelial ovarian cancer (EOC). Materials and Methods. In the present multicenter study, pretherapeutic plasma fibrinogen levels were evaluated in 422 patients with EOC. Plasma fibrinogen levels were correlated with clinicopathological parameters and patient survival. RESULTS: The mean (standard deviation) pretherapeutic plasma fibrinogen level was 450.0 (150.1) mg/dl. Elevated plasma fibrinogen levels were associated with advanced tumor stage (p = .01) and the presence of a postoperative residual tumor mass (p < .001), but not with histological grade (p = .1) and histological type (p = .8). In a multivariate Cox regression model, tumor stage (p < .001 and p < .001), postoperative residual tumor mass (p = .001 and p = .008), and plasma fibrinogen level (p < .001 and p = .002), but not histological type (p = .8 and p = .2), patient age (p = .9 and p = .9), and serum cancer antigen 125 (p = 0.2 and p = 0.3) and C-reactive protein (p = .2 and p = .3) levels, were associated with disease-free and overall survival, respectively. Histological grade was associated with overall but not with disease-free survival (p = .01 and p = .8), respectively. CONCLUSIONS: Pretherapeutic plasma fibrinogen levels can be used as an independent prognostic parameter in patients with EOC.