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Background: This study aimed to investigate the role of radical prostatectomy (RP) among clinical nodal metastasis prostate cancer and whether histological confirmation of lymph node metastasis through surgery can help with treatment. Patients and Methods: After excluding patients with distant metastatic prostate cancer or neoadjuvant androgen deprivation therapy, 42 patients with clinical nodal metastasis who underwent RP at our institution were included in the study. We classified them as having or not having pathological lymph node metastasis. Clinicopathologic data were analyzed in this retrospective chart review. Kaplan–Meier analysis was used to calculate the estimated castration-resistant prostate cancer (CRPC)-free survival, biochemical recurrence (BCR)-free survival, and cancer-specific survival (CSS). Results: There is no significant difference in age, presence of diabetes mellitus, hypertension, BCR time, CRPC time, overall survival, salvage RT rate, and initial prostate-specific antigen level between the two groups. However, there is a significant difference in the pathology N1 group in terms of pathological T stage, pathologic Gleason score, BCR rate, CRPC rate, and CSS. A multivariate Cox proportional hazard regression analysis was used to identify predictors of CRPC-free survival. Patients with pathological lymph node metastasis had a shorter CRPC-free survival [hazard ratio (HR) 4.87; 95% confidence interval (CI) 1.25–19.00, p = 0.02]. Conclusion: Radical prostatectomy can confirm lymph node metastasis. Although pathologic diagnosis has no effect on time to BCR and CPRC, because it affects BCR rate, CRPC rate, and CSS, an accurate pathological diagnosis obtained through surgery is beneficial in the treatment of clinical lymph node metastasis prostate cancer. [ABSTRACT FROM AUTHOR]

The presence of lymph node (LN) positivity in endometrial adenocarcinoma (EAC) patients guides adjuvant treatment, but recommendations regarding LN evaluation at the time of primary surgery remain variable. Primary pathologic tumor characteristics may predict risk of LN involvement in EAC patients with limited LN evaluation. Patients diagnosed between 2004-2016 with pathologic T1-T2 EAC in the National Cancer Database who had at least one lymph node sampled at the time of surgery were included. Pathologic primary tumor predictors of LN involvement were identified using logistic regression. To predict overall, pelvic only, and paraaortic and/or pelvic LN involvement, nomograms were generated. Among 57,810 EAC patients included, 4002 were node positive. On multivariable analysis, increasing pathologic tumor category (pT2 versus pT1a, odds ratio (OR) 5.43, 95% confidence interval (CI) 4.89-6.02, p < 0.001), increasing pathologic tumor grade (grade 3 versus grade 1, OR 1.62, 95% CI 1.47-1.79, p < 0.001), increase in tumor size per centimeter (OR 1.05, 95% CI 1.04-1.06, p < 0.001), and presence of lymphovascular invasion (LVI) (OR 6.33, 95% CI 5.87-6.83, p<0.001) were predictive of overall LN positivity. The presence of LVI was a stronger predictor of paraaortic LN involvement (OR 6.43, 95% CI 5.55-7.47, p < 0.001) than pelvic LN involvement (OR 5.42, 95% CI 4.98-5.90, p < 0.001) in multivariable analysis. For patients with limited LN evaluation, pathologic tumor features can be used to estimate the risk of pelvic or paraaortic LN involvement. This information may inform adjuvant treatment decisions and guide future studies. [ABSTRACT FROM AUTHOR]

Objective: To assess the oncological benefit of adjuvant chemotherapy (AC) in node positive (ypN+) rectal cancer after neoadjuvant chemoradiotherapy and radical surgery. Background: The evidence for AC after total mesorectal excision for locally advanced rectal cancer is conflicting and the net survival benefit is debated. Methods: An international multicenter comparative cohort study was performed comparing oncological outcomes in tertiary rectal cancer centers from the Netherlands and France. Patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy followed by total mesorectal excision surgery and with positive lymph nodes on histologic examination (ypN+) were included for analysis. Kaplan-Meier curves were generated to compare disease-free (DFS) and overall survival in AC and non-AC groups. Results: Of 1265 patients screened, a total of 239 rectal cancer patients with ypN+ disease were included. Demographic and clinical characteristics were similar in both groups. Higher systemic recurrence rates were observed in the non-AC group compared with those who received AC [32.0% (n=40) vs 17.5% (n=11), respectively, P =0.034]. DFS at 1 and 5 years postoperatively were significantly better in the AC group (92% vs 80% at 1 year; 72% vs 51% at 5 years, P =0.024), whereas no difference in overall survival was observed. Conclusions: In this multicenter comparative cohort study, we identified an oncological benefit of AC in both systemic recurrence and DFS in ypN+ rectal cancer patients. From this data, systemic chemotherapy continues to confer oncological benefit in locally advanced ypN+ rectal cancer. [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to develop and validate a nomogram for predicting cancer-specific survival (CSS) in lymph- node- positive rectal cancer patients after radical proctectomy. Methods: In this study, we analyzed data collected from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. In addition, in a 7:3 randomized design, all patients were split into two groups (development and validation cohorts). CSS predictors were selected via univariate and multivariate Cox regressions. The nomogram was constructed by analyzing univariate and multivariate predictors. The effectiveness of this nomogram was evaluated by concordance index (C-index), calibration plots, and receiver operating characteristic (ROC) curve. Based on the total score of each patient in the development cohort in the nomogram, a risk stratification system was developed. In order to analyze the survival outcomes among different risk groups, Kaplan-Meier method was used. Results: We selected 4,310 lymph- node- positive rectal cancer patients after radical proctectomy, including a development cohort (70%, 3,017) and a validation cohort (30%, 1,293). The nomogram correlation C-index for the development cohort and the validation cohort was 0.702 (95% CI, 0.687-0.717) and 0.690 (95% CI, 0.665-0.715), respectively. The calibration curves for 3- and 5-year CSS showed great concordance. The 3- and 5-year areas under the curve (AUC) of ROC curves in the development cohort were 0.758 and 0.740, respectively, and 0.735 and 0.730 in the validation cohort, respectively. Following the establishment of the nomogram, we also established a risk stratification system. According to their nomogram total points, patients were divided into three risk groups. There were significant differences between the low-, intermediate-, and high-risk groups (p< 0.05). Conclusions: As a result of our research, we developed a highly discriminatory and accurate nomogram and associated risk classification system to predict CSS in lymph-node- positive rectal cancer patients after radical proctectomy. This model can help predict the prognosis of patients with lymph- node- positive rectal cancer. [ABSTRACT FROM AUTHOR]

Background: This study aimed to examine whether MPV is a useful prognostic marker and investigated whether MPV is a risk factor that helps identify patients with locally advanced-stage ESCC who will most likely benefit from adjuvant chemotherapy. Methods: Patients (n =1690) with histologically confirmed ESCC were diagnosed with locally advanced stage (pT3-4N0M0 and pT1-4N+M0) at Sichuan Cancer Hospital from 2009 to 2017. Clinicopathological factors and platelet-related values were tested for their associations with survival using univariate and multivariate Cox regression analyses. The optimal cut-off value for continuous variables was determined using the 'maxstat' R package. The KM curve continuous variable analysis was performed to identify the optimal cut-off value for MPV. Cumulative survival rates were determined using the Kaplan-Meier estimator and compared using the log-rank test. The survival analysis was performed using the 'survival' R package. All statistical analyses were performed using R software 4.1.3 (https://www.r-project.org/), and a two-sided p-value <0.05 was considered to indicate statistical significance. Results: Multivariate analysis indicated that low MPV was an important risk factor for overall survival in locally advanced ESCC, independent of classic clinicopathological factors. The optimal cut-off value of MPV (11.8 fL) was used to stratify high-risk patients. Patients with low mean platelet volumes had a worse prognosis than those with larger platelet volumes, according to Kaplan-Meier analysis and the log-rank test. Patients diagnosed with a pathological lymph node-positive stage with a low MPV (=11.8 fL) benefited from postoperative chemotherapy, but not those with a high-level MPV (>11.8 fL). Conclusion: MPV served as an independent predictor of prognosis of locally advanced-stage ESCC and predicted a survival benefit conferred by postoperative adjuvant chemotherapy in lymph node-positive ESCC. [ABSTRACT FROM AUTHOR]

Background: Luminal B-like human epidermal growth factor receptor 2 negative (Luminal B [HER2−]) is the most common molecular subtype of breast cancer (BC). Since the relationship between Luminal B (HER2−) BC and liver metastasis (LM) is poorly defined, this retrospective study aimed to develop an LM risk nomogram for patients with lymph node-related (N + Luminal B [HER2−]) BC. Methods: Data were obtained for patients initially diagnosed with BC from the Tianjin Medical University Cancer Institute and Hospital. There were 30,975 Chinese female patients with stage I–III BC and follow-up confirming 1217 subsequent patients with LM, and 427 patients with N + Luminal B (HER2−). The LM risk was assessed using Cox proportional hazards regression, histogram, Venn diagram, and Kaplan–Meier survival analysis, with further analysis for patients with N + Luminal B (HER2−) BC. A nomogram was established based on the N + Luminal B (HER2−) BC data, which was validated using calibration plots. Results: The median age of 427 patients with N + Luminal B (HER2−) liver metastasis of breast cancer (BCLM) was 49 years. The largest number of patients with BCLM was diagnosed between the second to the 6th year, the longest interval from initial BC diagnosis to subsequent LM was 145 months. The patients with LM as the first site of distant metastasis which is associated with better survival were analyzed by Kaplan–Meier. The nomogram was constructed for the risk of LM that included age, menstrual status, unilateral oophorectomy, pregnancy, hepatitis B antigen, region of residence, tumor size, lymph node, clavicular lymph nodes, progesterone receptor, and lymph vessel invasion. Conclusion: We described the clinicopathological characteristics of patients with stage I–III BC, and constructed a nomogram for calculating personalized LM probabilities for patients with N + Luminal B (HER2−), which could guide future prolonged or early extensive treatment decisions. [ABSTRACT FROM AUTHOR]

Introduction: The National Comprehensive Cancer Network recommends external beam radiotherapy (EBRT) combined with androgen deprivation therapy (ADT) as the preferred treatment option for newly diagnosed node-positive (cN1) prostate cancer (PCa) patients. However, implementation of positron emission tomography targeting prostate-specific membrane antigen (PSMA-PET) in the staging of primary PCa patients has a significant impact on RT treatment concepts. This study aims to evaluate outcomes and their respective risk factors on patients with PSMA-PET-based cN1 and/or cM1a PCa receiving primary RT and ADT. Methods: Forty-eight patients with cN0 and/or cM1a PCa staged by [18F]PSMA-1007-PET (n = 19) or [68Ga]PSMA-11-PET (n = 29) were retrospectively included. All patients received EBRT to the pelvis ± boost to positive nodes, followed by boost to the prostate. The impact of different PET-derived characteristics such as maximum standard uptake value (SUVmax) and number of PET-positive lymph nodes on biochemical recurrence-free survival (BRFS) (Phoenix criteria) and metastasis-free survival (MFS) was determined using Kaplan–Meier and Cox proportional hazard regression analyses. Results: Median follow-up was 24 months. Median initial serum prostate-specific antigen was 20.2 ng/ml (IQR 10.2–54.2). Most patients had cT stage ≥ 3 (63%) and ISUP grade ≥ 3 (85%). Median dose to the prostate, elective nodes, and PET-positive nodes was 75 Gy, 45 Gy, and 55 Gy, respectively. Ninety percent of patients received ADT with a median duration of 9 months (IQR 6–18). In univariate analysis, cM1a stage (p = 0.03), number of >2 pelvic nodes (p = 0.01), number of >1 abdominal node (p = 0.02), and SUVmax values ≥ median (8.1 g/ml for 68Ga-PSMA-11 and 7.9 g/ml for 18F-PSMA-1007) extracted from lymph nodes were significantly associated with unfavorable BRFS, but classical clinicopathological features were not. Number of >2 pelvic nodes (n = 0.03), number of >1 abdominal node (p = 0.03), and SUVmax values ≥ median extracted from lymph nodes were associated with unfavorable MFS. In multivariate analysis, number of >2 pelvic lymph nodes was significantly associated with unfavorable BRFS (HR 5.2, p = 0.01) and SUVmax values ≥ median extracted from lymph nodes had unfavorable MFS (HR 6.3, p = 0.02). Conclusion: More than 2 PET-positive pelvic lymph nodes are associated with unfavorable BRFS, and high SUVmax values are associated with unfavorable MFS. Thus, the number of PET-positive lymph nodes and the SUVmax value might be relevant prognosticators to identify patients with favorable outcomes. [ABSTRACT FROM AUTHOR]

IntroductionThe National Comprehensive Cancer Network recommends external beam radiotherapy (EBRT) combined with androgen deprivation therapy (ADT) as the preferred treatment option for newly diagnosed node-positive (cN1) prostate cancer (PCa) patients. However, implementation of positron emission tomography targeting prostate-specific membrane antigen (PSMA-PET) in the staging of primary PCa patients has a significant impact on RT treatment concepts. This study aims to evaluate outcomes and their respective risk factors on patients with PSMA-PET-based cN1 and/or cM1a PCa receiving primary RT and ADT.MethodsForty-eight patients with cN0 and/or cM1a PCa staged by [18F]PSMA-1007-PET (n = 19) or [68Ga]PSMA-11-PET (n = 29) were retrospectively included. All patients received EBRT to the pelvis ± boost to positive nodes, followed by boost to the prostate. The impact of different PET-derived characteristics such as maximum standard uptake value (SUVmax) and number of PET-positive lymph nodes on biochemical recurrence-free survival (BRFS) (Phoenix criteria) and metastasis-free survival (MFS) was determined using Kaplan–Meier and Cox proportional hazard regression analyses.ResultsMedian follow-up was 24 months. Median initial serum prostate-specific antigen was 20.2 ng/ml (IQR 10.2–54.2). Most patients had cT stage ≥ 3 (63%) and ISUP grade ≥ 3 (85%). Median dose to the prostate, elective nodes, and PET-positive nodes was 75 Gy, 45 Gy, and 55 Gy, respectively. Ninety percent of patients received ADT with a median duration of 9 months (IQR 6–18). In univariate analysis, cM1a stage (p = 0.03), number of >2 pelvic nodes (p = 0.01), number of >1 abdominal node (p = 0.02), and SUVmax values ≥ median (8.1 g/ml for 68Ga-PSMA-11 and 7.9 g/ml for 18F-PSMA-1007) extracted from lymph nodes were significantly associated with unfavorable BRFS, but classical clinicopathological features were not. Number of >2 pelvic nodes (n = 0.03), number of >1 abdominal node (p = 0.03), and SUVmax values ≥ median extracted from lymph nodes were associated with unfavorable MFS. In multivariate analysis, number of >2 pelvic lymph nodes was significantly associated with unfavorable BRFS (HR 5.2, p = 0.01) and SUVmax values ≥ median extracted from lymph nodes had unfavorable MFS (HR 6.3, p = 0.02).ConclusionMore than 2 PET-positive pelvic lymph nodes are associated with unfavorable BRFS, and high SUVmax values are associated with unfavorable MFS. Thus, the number of PET-positive lymph nodes and the SUVmax value might be relevant prognosticators to identify patients with favorable outcomes.

Objective: To determine whether repeated [18F]fluorodeoxyglucose‐positron emission tomography/computed tomography (FDG‐PET‐CT) scans can predict increased cancer‐specific survival (CSS) after induction chemotherapy followed by radical cystectomy (RC). Patients and Methods: Between 2007 and 2018, 86 patients with clinically lymph node (LN)‐positive bladder cancer (T1–T4, N1–N3, M0–M1a) were included and underwent a repeated FDG‐PET‐CT during cisplatin‐based induction chemotherapy. The 71 patients that had a response to chemotherapy underwent RC. Response to chemotherapy was evaluated in LNs through repeated FDG‐PET‐CT and stratified as partial response or complete response using three different methods: maximum standardised uptake value (SUVmax), adapted Deauville criteria, and total lesion glycolysis (TLG). Progression‐free survival (PFS) and CSS were analysed for all three methods by Cox regression analysis. Results: After a median follow‐up of 40 months, 15 of the 71 patients who underwent RC had died from bladder cancer. Using SUVmax and the adapted Deauville criteria, multivariable Cox regression analyses adjusting for age, clinical tumour stage and LN stage showed that complete response was associated with increased PFS (hazard ratio [HR] 3.42, 95% confidence interval [CI] 1.20–9.77) and CSS (HR 3.30, 95% CI 1.02–10.65). Using TLG, a complete response was also associated with increased PFS (HR 5.17, 95% CI 1.90–14.04) and CSS (HR 6.32, 95% CI 2.06–19.41). Conclusions: Complete metabolic response with FDG‐PET‐CT predicts survival after induction chemotherapy followed by RC in patients with LN‐positive bladder cancer and comprises a novel tool in evaluating response to chemotherapy before surgery. This strategy has the potential to tailor treatment in individual patients by identifying significant response to chemotherapy, which motivates the administration of a full course of induction chemotherapy with a higher threshold for suspending treatment due to toxicity and side‐effects. [ABSTRACT FROM AUTHOR]

Molecular prognostic factors for individualized treatment of squamous cell carcinoma (SCC) are poorly defined. Our study developed and validated a novel molecular tools aid in preinguinal and postinguinal lymphadenectomy risk stratification in node‐positive penile SCC. Patients with node‐positive penile SCC who underwent inguinal or ilioinguinal lymphadenectomy were divided into three cohorts: a discovery set, a development set and a validation set. The local ethics committee approved the study. The primary endpoint was cancer‐specific survival (CSS). At the discovery stage, 17 CpG sites were significantly associated with CSS. In the development set, we constructed a 3‐CpG‐based prognostic score for survival prediction. The hazard ratio (HR) of the panel (dichotomized using the optimal cutoff) was 5.8 in the multivariate analyses (P <.001). The addition of the methylation score significantly improved the pN‐stage C‐index from 0.70 to 0.79 (incremental C = 0.09, P <.001). In the validation set, the methylation panel showed a HR of 9.9 in the multivariate analyses. The addition of the molecular marker improved the pN‐stage C‐index from 0.69 to 0.78 (incremental C = 0.09, P <.001). The methylation score remarkably separated survival curves in different pN stages, which indicate that the tool can be applied to tailor the treatment in both preinguinal and postinguinal lymphadenectomy settings. We developed and validated a prognostic methylation panel for node‐positive penile SCC. The tool may aid in the risk stratification of the population with heterogeneous outcomes and needs prospective validation. Patients in high‐risk group may benefit from more aggressive therapy or clinical trials. What's new? Patients with node‐positive penile cancer are not a homogeneous group, and new prognostic markers other than the pN stage are urgently needed. Here, the authors developed and validated a methylation score to predict survival outcome in node‐positive penile cancer. In pre‐inguinal lymphadenectomy patients, the risk score provides objective information supporting the decision‐making process for neoadjuvant therapy. In post‐inguinal lymphadenectomy patients, the risk score in conjunction with the pN stage can help tailor the multimodality treatment. The risk score can be easily measured from primary penis tumor samples and objectively evaluates the survival outcomes of patients, with an accuracy above 70%. [ABSTRACT FROM AUTHOR]

Objective: To utilize a national dataset to compare outcomes and demonstrate trends in treatment for lymph node positive bladder cancer (N+ BC).Methods: The National Cancer Database (2006-2014) was queried for cT2-4N1-3M0 N+ BC patients treated with radical cystectomy alone (RC), neoadjuvant chemotherapy (NAC), adjuvant chemotherapy (AC), chemoradiation (CRT), chemotherapy alone (CT), or no definitive treatment (NT). Survival by treatment was analyzed using Kaplan-Meier and multivariable Cox-proportional hazards regression. Pathologic down-staging was analyzed using univariable and multivariable logistic regression models. A univariable logistic regression model of treatment by year identified treatment trends.Results: Among 3241 patients (cN1, 46%; cN2, 44%; cN3 10%), the majority underwent combined chemotherapy and RC (NAC, 418; AC, 591; RC, 567; CRT, 392; CT, 1068; NT, 205). Overall survival did not differ between NAC and AC, but both had improved survival compared to RC. All other treatment groups had worse survival outcomes compared to NAC. Down-staging to pT0 (adjusted odds ratio = 26.39) and pN0 (adjusted odds ratio = 6.88) was higher for NAC than RC. Utilization of NAC has increased, AC and RC has declined, and CRT and NT is unchanged.Conclusion: Combined chemotherapy and RC demonstrates best survival outcomes for N+ BC, with complete pathologic response to pT0N0 after NAC associated with a 5-year overall survival rate of ∼85%. However, there is no significant difference between NAC and AC. CRT is associated with worse oncologic outcomes compared to RC with perioperative chemotherapy, but improved survival compared to RC or CT. [ABSTRACT FROM AUTHOR]

Background: Patients with early-stage hormone receptor positive, human epidermal growth factor receptor-2 (HER2) negative invasive breast cancer with 1-3 positive lymph nodes (N1) often undergo surgical excisions followed by adjuvant chemotherapy (ACT). Many patients have no benefit from ACT and receive unnecessary, costly treatment often associated with short- and long-term adverse events (AEs). Gene expression profiling (GEP) assays, such as the 21-gene assay (i.e. the Oncotype DX assay), can identify patients at higher risk for recurrence who may benefit from ACT. However, the budgetary consequence of using the Oncotype DX assay versus no GEP testing in the Netherlands is unknown. Our study therefore assessed it using a cost-consequence model., Methods: A validated model was used to create the N1 model. The model compared the costs and consequences of using the Oncotype DX assay versus no GEP testing and MammaPrint, and subsequent ACT use with corresponding costs for chemotherapy, treatment of AEs, productivity losses, GEP testing, and treatment of recurrences, according to the Oncotype DX results. The model time horizon was 5 years., Results: Costs for the total population amounted to €8.0 million (M), €16.2 M, and €9.5 M, and cost per patient amounted to €13,540, €27,455, and €16,154 for using the Oncotype DX assay, no GEP testing, and MammaPrint, respectively. Total cost savings of using the Oncotype DX assay amounted to €8.2 M versus no GEP testing and €1.5 M versus MammaPrint. Using the Oncotype DX assay would result in fewer patients receiving ACT and thus fewer AEs, sick days, and hospitalizations, leading to overall cost savings compared with no GEP testing and MammaPrint., Conclusions: Implementing Oncotype DX testing in this population can prevent unnecessary overtreatment, reducing clinical and economic burden on the patient and Dutch healthcare system.

Aim Of the Study: Although surgery is considered to be curative treatment, recurrence rates are high in gastric cancer. Adjuvant 5-fluorouracil (5-FU) based chemoradiotherapy has been shown to improve the prognosis. We compared tolerability and efficacy of the two different chemotherapy regimens; 5-FU/leucovorin (LV) versus cisplatin with capecitabine (XP) combined with radiotherapy (RT) in the adjuvant therapy of the lymph node positive locally advanced gastric cancer.Materials and Methods: Totally, 104 patients who underwent curative surgery with lymph node resection were evaluated, respectively. Patients were stratified two group based on the adjuvant chemoradiotherapy regimen. Group 1 (n = 46) received XP followed capecitabine with RT (XRT) then XP. Group 2 (n = 58) received 5-FU/LV combined with RT postoperatively. Two groups were compared based on clinicopathological parameters. Factors related with disease-free survival (DFS) and overall survival (OS) were analyzed.Results: Totally, 32 patients had recurrent disease, and there was no difference between two groups. While peritoneal metastasis was more common in XP arm, distant metastasis was commonly seen in 5-FU/LV arm. There was no significant difference between two groups in regard of Grade 3/4 toxicitis; hematologic toxicities were more in 5-FU/LV group than XP arm. In addition, dose modification because of toxicities were more frequent in 5-FU/LV arm (P = 0.003). For all groups, lymph node dissection type was related with DFS, surgical margin and recurrence were important for OS.Conclusion: XP-XRT regimen is well tolerated with lower toxicity compared the standard 5-FU/LV-RT. Although there is no difference with respect to outcome, patients with XP arm without the necessity of intravenous catheter admitted hospital less frequent than bolus5-FU/LV arm. [ABSTRACT FROM AUTHOR]

Optimal management of node-positive prostate cancer patients after prostatectomy remains a challenge. We evaluated clinically localized patients who demonstrated node positivity and identified predictors for secondary treatment. From 2010 to 2015, clinically localized prostate cancer patients who underwent robot prostatectomy with extended lymphadenectomy and node-positive disease on pathologic analysis were identified. Clinical N1, M1 or salvage cases were excluded. Patients were stratified based on secondary treatments. Kaplan-Meier method was used to determine the time to biochemical and metastatic recurrence. Multivariate logistic regression was used to identify predictors for additional treatment. 145 patients (45 no additional therapy, 47 adjuvant, 53 salvage) had a median follow-up of 31.2 months. Salvage patients had higher median pre-operative prostate-specific antigen (10.8 vs. 9.7 vs. 8.2, p = 0.1), higher percentage of pathologic Gleason ≥8 (50.9 vs. 38.3% and 22.2%, p < 0.01), and higher median-positive nodes (3 vs. 1 and 1, p < 0.0001) compared to adjuvant and no treatment groups, respectively. Pathologic Gleason ≥8 (OR = 3.5, p = 0.007) and positive nodes ≥2 (OR = 3.3, p = 0.006) were associated with additional therapy. In the no treatment group, two-year estimated BCRFS was 74.3%. Two-year metastatic recurrence-free rates for no treatment, adjuvant and salvage groups were 100, 87.5, and 80.9%, respectively (p = 0.01). Observation is a viable alternative for low metastatic burden patients. In the largest series of node-positive patients from robotic prostatectomy and extended lymphadenectomy, those with pathologic Gleason ≥8 and positive lymph nodes ≥2 were more likely to receive additional treatment. [ABSTRACT FROM AUTHOR]

The invasive and metastatic phenotypes of breast cancer correlate with high recurrence rates and poor survival outcomes. Transforming growth factor-β (TGFβ) promotes tumor progression and metastasis in aggressive breast cancer. Here, we identified the kisspeptin KiSS1 as a downstream target of canonical TGFβ/Smad2 pathway in triple negative breast cancer cells. We also found KiSS1 expression to be required for TGFβ-induced cancer cell invasion. Indeed, knockdown expression of KiSS1 blocked TGFβ-mediated cancer cell invasion as well as metalloproteinase (MMP9) expression and activity. Interestingly, Kisspeptin-10 (KP-10), the smallest active form of kisspeptin also stimulates cancer cell invasive behavior through activation of MAPK/Erk pathway. We described a positive feedback loop between KiSS1 and p21 downstream of TGFβ, further contributing to TGFβ-induced cancer cell invasion. Lastly, we explored both the clinical utility of KiSS1 as a lymph node involvement predictive tool and its potential as a therapeutic target. We found KiSS1 high expression to correlate with lymph node positive status. Furthermore, blocking KiSS1 using a specific small peptide antagonist (p234) impaired TGFβ-mediated cell invasion and MMP9 induction. Together, our results define an essential role of KiSS1 in regulating TGFβ pro-invasive effects and define KiSS1 as a therapeutic new target for triple negative breast cancer. [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to develop and validate a nomogram for predicting cancer-specific survival (CSS) in lymph- node- positive rectal cancer patients after radical proctectomy., Methods: In this study, we analyzed data collected from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. In addition, in a 7:3 randomized design, all patients were split into two groups (development and validation cohorts). CSS predictors were selected via univariate and multivariate Cox regressions. The nomogram was constructed by analyzing univariate and multivariate predictors. The effectiveness of this nomogram was evaluated by concordance index (C-index), calibration plots, and receiver operating characteristic (ROC) curve. Based on the total score of each patient in the development cohort in the nomogram, a risk stratification system was developed. In order to analyze the survival outcomes among different risk groups, Kaplan-Meier method was used., Results: We selected 4,310 lymph- node- positive rectal cancer patients after radical proctectomy, including a development cohort (70%, 3,017) and a validation cohort (30%, 1,293). The nomogram correlation C-index for the development cohort and the validation cohort was 0.702 (95% CI, 0.687-0.717) and 0.690 (95% CI, 0.665-0.715), respectively. The calibration curves for 3- and 5-year CSS showed great concordance. The 3- and 5-year areas under the curve (AUC) of ROC curves in the development cohort were 0.758 and 0.740, respectively, and 0.735 and 0.730 in the validation cohort, respectively. Following the establishment of the nomogram, we also established a risk stratification system. According to their nomogram total points, patients were divided into three risk groups. There were significant differences between the low-, intermediate-, and high-risk groups (p< 0.05)., Conclusions: As a result of our research, we developed a highly discriminatory and accurate nomogram and associated risk classification system to predict CSS in lymph-node- positive rectal cancer patients after radical proctectomy. This model can help predict the prognosis of patients with lymph- node- positive rectal cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhong, Ju, Liu, He, Wang, Yu, Lu and Li.)

Objectives The purpose of this study was to examine the impact of adjuvant radiation on overall survival (OS) and cancer specific survival (CSS) in patients with lymph node (LN) positive endometrial cancer. Methods We analyzed all women diagnosed with FIGO stage IIIC endometrial adenocarcinoma in the Surveillance, Epidemiology, and End Results database from 2004 to 2012 ( n = 2177). Patients not undergoing surgery or with missing treatment information were excluded. Chi-squared tests were used to compare predictors of treatment received. Cox proportional hazards model and Kaplan-Meier method were used to assess OS and CSS. Results The median age was 60 (27–84) and the median follow-up was 31 months (2–107). Adjuvant radiation was administered to 1248 (60.3%) patients. A total of 1363 (65.9%) patients had pelvic LN involvement while 658 (31.8%) had para-aortic involvement. The 3-year actuarial OS for patients with and without radiation was 80.5% and 67.6%, respectively ( p < 0.001). The 3-year actuarial CSS for patients with and without radiation was 83.4% and 73%, respectively ( p < 0.001). On multivariable analysis, receipt of radiotherapy remained associated with OS (HR 0.61 95% CI 0.51–0.74) and CSS (HR 0.65, 95% CI 0.53–0.80). After propensity matching, radiotherapy continued to be associated with an improved OS (HR 0.65 95% CI 0.54–0.78) and CSS (HR 0.65 95% CI 0.53–0.81). The addition of brachytherapy was not associated with OS or CSS. Conclusions In this large population registry analysis, adjuvant radiation was associated with improved OS and CSS in patients with LN positive endometrial cancer. Prospective data is needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Objective To evaluate the effect of adjuvant chemotherapy ( AC) on mortality after radical nephroureterectomy ( RNU) for upper tract urothelial carcinoma ( UTUC) with positive lymph nodes ( LNs) and to identify patient subgroups that are most likely to benefit from AC. Patients and methods We retrospectively analysed data of 263 patients with LN-positive UTUC, who underwent full surgical resection. In all, 107 patients (41%) received three to six cycles of AC, while 156 (59.3%) were treated with RNU alone. UTUC-related mortality was evaluated using competing-risks regression models. Results In all patients (Tall N+), administration of AC had no significant impact on UTUC-related mortality on univariable ( P = 0.49) and multivariable ( P = 0.11) analysis. Further stratified analyses showed that only N+ patients with pT3-4 disease benefited from AC. In this subgroup, AC reduced UTUC-related mortality by 34% ( P = 0.019). The absolute difference in mortality was 10% after the first year and increased to 23% after 5 years. On multivariable analysis, administration of AC was associated with significantly reduced UTUC-related mortality (subhazard ratio 0.67, P = 0.022). Limitations of this study are the retrospective non-randomised design, selection bias, absence of a central pathological review and different AC protocols. Conclusions AC seems to reduce mortality in patients with pT3-4 LN-positive UTUC after RNU. This subgroup of LN-positive patients could serve as target population for an AC prospective randomised trial. [ABSTRACT FROM AUTHOR]

Objective To compare outcomes of patients with lymph node ( LN)-positive urothelial carcinoma of the bladder ( UCB) treated with or without cisplatin-based combined adjuvant chemotherapy ( AC) after radical cystectomy ( RC). Patients and Methods We retrospectively analysed 1523 patients with LN-positive UCB, who underwent RC with bilateral pelvic LN dissection. All patients had no evidence of disease after RC. AC was administered within 3 months. Competing-risks models were applied to compare UCB-related mortality. Results Of the 1523 patients, 874 (57.4%) received AC. The cumulative 1-, 2- and 5-year UCB-related mortality rates for all patients were 16%, 36% and 56%, respectively. Administration of AC was associated with an 18% relative reduction in the risk of UCB-related death (subhazard ratio 0.82, P = 0.005). The absolute reduction in mortality was 3.5% at 5 years. The positive effect of AC was detectable in patients aged ≤70 years, in women, in pT3-4 disease, and in those with a higher LN density and lymphovascular invasion. This study is limited by its retrospective and non-randomised design, selection bias, the absence of central pathological review and lack in standardisation of LN dissection and cisplatin-based protocols. Conclusion AC seems to reduce UCB-related mortality in patients with LN-positive UCB after RC. Younger patients, women and those with high-risk features such as pT3-4 disease, a higher LN density and lymphovascular invasion appear to benefit most. Appropriately powered prospective randomised trials are necessary to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: This study aimed to examine whether MPV is a useful prognostic marker and investigated whether MPV is a risk factor that helps identify patients with locally advanced-stage ESCC who will most likely benefit from adjuvant chemotherapy., Methods: Patients (n =1690) with histologically confirmed ESCC were diagnosed with locally advanced stage (pT3-4N0M0 and pT1-4N+M0) at Sichuan Cancer Hospital from 2009 to 2017. Clinicopathological factors and platelet-related values were tested for their associations with survival using univariate and multivariate Cox regression analyses. The optimal cut-off value for continuous variables was determined using the 'maxstat' R package. The KM curve continuous variable analysis was performed to identify the optimal cut-off value for MPV. Cumulative survival rates were determined using the Kaplan-Meier estimator and compared using the log-rank test. The survival analysis was performed using the 'survival' R package. All statistical analyses were performed using R software 4.1.3 (https://www.r-project.org/), and a two-sided p-value <0.05 was considered to indicate statistical significance., Results: Multivariate analysis indicated that low MPV was an important risk factor for overall survival in locally advanced ESCC, independent of classic clinicopathological factors. The optimal cut-off value of MPV (11.8 fL) was used to stratify high-risk patients. Patients with low mean platelet volumes had a worse prognosis than those with larger platelet volumes, according to Kaplan-Meier analysis and the log-rank test. Patients diagnosed with a pathological lymph node-positive stage with a low MPV (≤11.8 fL) benefited from postoperative chemotherapy, but not those with a high-level MPV (>11.8 fL)., Conclusion: MPV served as an independent predictor of prognosis of locally advanced-stage ESCC and predicted a survival benefit conferred by postoperative adjuvant chemotherapy in lymph node-positive ESCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Zhang, Tang, Jiang, Jiang and Wang.)

Metabolic diseases like diabetes and obesity are major risk factors for breast cancer. Aberrant expression of metabolic effectors such as fibroblast growth factor 19 (FGF19) could be therefore associated with the disease. The expression of FGF19 was examined in 193 archival breast tumor samples by immunohistochemistry and evaluated semi-quantitatively by determining the staining index and correlating it with clinicopathological parameters using Fisher's exact test. The correlation between FGF19 expression and 5-year disease-specific survival rate was determined using the univariate Kaplan-Meier analysis. The prognostic value of FGF19 expression was evaluated using the multivariate Cox regression analysis. Of the 193 tumors analyzed, 40 % were classified with low FGF19 expression, whereas 60 % were categorized as tumors with high FGF19 expression. There was a highly significant correlation between high FGF19 expression and patients' age ( p = 0.008) as well as 5-year disease-specific survival ( p = 0.001). However, FGF19 expression did not show any significant correlations with other clinicopathological parameters, including hormonal status, tumor grade, tumor size, or lymph node status. Univariate Kaplan-Meier log rank analysis showed that patients with high FGF19 expression exhibited a significantly shorter disease-specific 5-year survival ( p = 0.007). This effect was exacerbated by lymph node metastasis ( p = 0.001), negative estrogen receptor (ER) status ( p = 0.002), or old age ( p = 0.013). Multivariate analysis showed that high FGF19 expression could be an independent prognostic marker of disease-specific survival in breast cancer patients ( p = 0.030). Quantification of FGF19 expression appears to provide valuable prognostic information in breast cancer, particularly in older patients with lymph node metastasis and negative ER status. [ABSTRACT FROM AUTHOR]

The recurrence score derived from the 21-gene Oncotype DX assay is both prognostic and predictive of adjuvant chemotherapy benefit in node-negative, estrogen-receptor-positive breast cancer patients treated with tamoxifen. This has led to a remarkable shift in the treatment paradigm, with a sizeable number of patients being able to avoid adjuvant chemotherapy. The recurrence score was then analyzed in a large retrospective study with node-positive, estrogen-receptor-positive patients, in which it demonstrated both prognostic and predictive abilities. This review introduces the clinical trials that validated the Oncotype DX assay in the node-negative population, highlights the studies evaluating the utility of the assay in node-positive patients, examines the impact of the assay results on treatment decisions, and discusses the health outcomes and health care expenditures associated with this assay. [ABSTRACT FROM AUTHOR]