5-year Cancer-specific Survival Research Articles

Clinical outcomes of adjuvant taxane plus anthracycline versus taxane-based chemotherapy regimens in older adults with node-positive, triple-negative breast cancer: A SEER–Medicare study

BackgroundTriple-negative breast cancer (TNBC) is a subtype of breast cancer associated with an aggressive clinical course. Adjuvant chemotherapy reduces the risk of recurrence and improves survival in patients with node-positive TNBC. The benefit of anthracycline plus taxane (ATAX) regimens compared with non-anthracycline-containing, taxane-based regimens (TAX) in older women with node-positive TNBC is not well characterised. MethodsUsing the Surveillance, Epidemiology, and End Results–Medicare database, we identified 1106 women with node-positive TNBC diagnosed at age 66 years and older between 2010 and 2015. We compared patient clinical characteristics according to adjuvant chemotherapy regimen (chemotherapy versus no chemotherapy and ATAX versus TAX). Logistic regression was performed to estimate the odds ratios (OR) and 95% confidence intervals (CIs). Kaplan–Meier survival curves were generated to estimate 3-year overall survival (OS) and cancer-specific survival (CSS). Cox proportional hazard models were used to analyse OS and CSS while controlling for patient and tumour characteristics. ResultsOf the 1106 patients in our cohort, 767 (69.3%) received adjuvant chemotherapy with ATAX (364/767, 47.5%), TAX (297/767, 39%) or other regimens (106/767, 13.8%). Independent predictors of which patients were more likely to receive ATAX versus TAX included more extensive nodal involvement (≥4), age, marital/partner status and non-cardiac comorbidities. There was a statistically significant improvement in 3-year CSS (81.8% versus 71.4%) and OS (70.7% versus 51.3%) with the use of any chemotherapy in our cohort (P < 0.01). Three-year CSS and OS for patients who received ATAX versus TAX were similar at 82.8% versus 83.7% (P = 0.80) and 74.2% versus 72.7% (P = 0.79), respectively. There was a trend towards improved CSS and OS in patients with four or more positive lymph nodes who received ATAX versus TAX (hazard ratio 0.66, 95% CI: 0.36–1.23, P = 0.19 and hazard ratio 0.68, 95% CI: 0.41–1.14, P = 0.14, respectively). ConclusionAmong older women with node-positive TNBC, a majority of patients received adjuvant chemotherapy, which was associated with an improvement in CSS and OS. When compared with TAX chemotherapy, there was a trend towards better outcomes with ATAX for patients with ≥4 nodes.

Achieving a Textbook Outcome in Colon Cancer Surgery Is Associated with Improved Long-Term Survival

Colon cancer surgery is a complex clinical pathway and traditional quality metrics may exhibit significant variability between hospitals and healthcare providers. The Textbook Outcome (TO) is a composite quality marker capturing the fraction of patients, in whom all desired short-term outcomes of care are realised. The aim of the present study was to assess the TO in a series of non-metastatic colon cancer patients treated with curative intent, with emphasis on long-term survival. Stage I-III colon cancer patients, who underwent curative colectomy following the Complete Mesocolic Excision principles, were retrospectively identified from the institutional database. TO was defined as (i) hospital survival, (ii) radical resection, (iii) no major complications, (iv) no reintervention, (v) no unplanned stoma and (vi) no prolonged hospital stay or readmission. In total, 128 patients (male 61%, female 39%, mean age 70.7 ± 11.4 years) were included in the final analysis. Overall, 60.2% achieved a TO. The highest rates were observed for "hospital survival" and "no unplanned stoma" (96.9% and 97.7%), while the lowest rates were for "no major complications" and "no prolonged hospital stay" (69.5% and 75%). Older age, left-sided resections and pT4 tumours were factors limiting the chances of a TO. The 5-year overall and 5-year cancer-specific survival were significantly better in the TO versus non-TO subgroup (81% vs. 59%, p = 0.009, and 86% vs. 65%, p = 0.02, respectively). Outcomes in colon cancer surgery may be affected by patient-, doctor- and hospital-related factors. TO represents those patients who achieve the optimal perioperative results, and is furthermore associated with improved long-term cancer survival.

The use of the second thoracic vertebral landmark for skeletal muscle assessment and computed tomography-defined sarcopenia evaluation in patients with head and neck cancer.

The cross-sectional area (CSA) of skeletal muscle (SM) at the third lumbar vertebra (L3) is used to determine computed tomography (CT)-defined sarcopenia. We investigated the feasibility of SM assessment at the second thoracic vertebra (T2) in patients with head and neck cancer (HNC). Diagnostic PET-CT scans were used to develop a prediction model for L3-CSA using T2-CSA. Effectiveness of the model and cancer-specific survival (CSS) were investigated. Scans of 111 patients (85% male) were evaluated. The predictive formula: L3-CSA (cm2 )=174.15 + [0.212 × T2-CSA (cm2 )] - [40.032 × sex] - [0.928 × age (years)] + [0.285 × weight (kg)] had good correlation r= 0.796, ICC=0.882 (p< 0.001). SM index (SMI) mean difference (bias) was -3.6% (SD 10.2, 95% CI -8.7% to 1.3%). Sensitivity (82.8%), specificity (78.2%), with moderate agreement (ƙ= 0.540, p< 0.001). Worse 5-year CSS with lower quartile T2-SMI (51%, p= 0.003). SM at T2 can be effectively used for CT-defined sarcopenia evaluation in HNC.

Preoperative c-reactive protein and risk of major complications and mortality outcomes in patients undergoing surgery for renal cell carcinoma.

723 Background: C-reactive protein (CRP) has been demonstrated to be an independent predictor of survival outcomes in renal cell carcinoma (RCC). The use of biomarkers to predict post-surgical complications is not well studied. We sought to investigate predictive factors for major complications following surgery for RCC and delineate their impact on mortality outcomes. Methods: We performed a two-center retrospective analysis of patients who underwent partial (PN) and radical nephrectomy (RN) for RCC. Patients who had complications within 30 days after surgery were identified and the complications were scored using the Clavien-Dindo classification system. Patients were grouped based on whether they experienced 30-day major (Clavien ≥3) complications and whether they had elevated preoperative CRP defined as &gt;5mg/L. Primary outcome was non-cancer mortality (NCM), with secondary outcomes being all-cause (ACM) and cancer-specific (CSM) mortality. Multivariable analyses (MVA) were conducted to evaluate predictors for Clavien ≥3 complications, NCM, CSM, and ACM. Kaplan-Meier analyses (KMA) were performed to compare overall survival (OS), noncancer-specific survival (NCS), and cancer-specific survival (CSS) between patients with non-elevated and elevated preoperative CRP and between patients without and with 30-day Clavien ≥3 complications. Results: A total of 2,234 patients were analyzed [116 (5.2%) experienced Clavien ≥3 complications; median follow up 44 months]. MVA revealed that coronary artery disease (OR 2.37, p=0.005), elevated CRP (OR 2.25, p=0.004), PN (OR 2.79, p&lt;0.001), and open surgical approach (OR 1.74, p=0.049) were predictive of Clavien ≥3 complications. Additionally, MVA demonstrated that elevated CRP was an independent predictor of NCM (HR 2.50, p=0.009), CSM (HR 5.51, p&lt;0.001) and ACM (HR 4.04, p&lt;0.001), while presence of 30-day Clavien ≥3 complications was independently associated with worsened NCM (HR 3.05, p=0.042) but not CSM or ACM. KMA comparing non-elevated and elevated preoperative CRP revealed significant differences for 5-year OS (96.0% vs. 66.8%, p&lt;0.001), 5-year CSS (98.2% vs. 75.6%, p&lt;0.001), and 5-year NCS (97.6% vs. 87.7%, p&lt;0.001). KMA comparing patients without and with 30-day Clavien ≥3 complications revealed significant differences for 5-year OS (87.3% vs. 80.7%, p=0.015) and 5-year NCS (95.6% vs. 87.0%, p&lt;0.001), but not 5-year CSS (91.3% vs. 88.9%, p=0.601). Conclusions: In patients undergoing surgical resection for RCC, elevated preoperative CRP was an independent risk factor for development of 30-day Clavien ≥3 complications, while elevated CRP and development of Clavien ≥3 complications were associated with worsened NCM. Our findings suggest an interplay between major complications and NCM in patients who undergo surgery for RCC, with elevated preoperative CRP being a predictor for both.

Proposal for reclassification of upstaged T1 and T2 and pathological T3 RCC based on improved alignment of survival analyses.

732 Background: Patients with pathologically upstaged tumors have worse survival outcomes than their non-upstaged matched counterparts. However, we do know that original clinical tumor staging does still predict outcomes. We sought to examine if pathologic upstaging incrementally may more rationally stratify cancer specific survival outcomes. Methods: Multi-institutional (Emory, TMDU, UCSD) retrospective analysis of patients with renal cell carcinoma who underwent partial or radical nephrectomy between 1998-2020. Patients were divided into cT1 upstaged to pT3 (cT1/pT3), cT2 non-upstaged (cT2/pT2), cT2 upstaged to pT3 (cT2/pT3), and cT3 non-upstaged (cT3/pT3). Patients were analyzed for demographics, clinical parameters, and post-surgical outcomes. Primary outcome was cancer specific mortality (CSM). Secondary outcomes were all cause mortality and recurrence free survival. Cox regression was utilized to analyze factors associated with outcomes. Kaplan Meier analysis (KMA) was performed to analyze 5-year cancer specific survival. ROC analysis was utilized to compare predictive value of AJCC 8th edition TNM staging vs proposed staging. Results: 1093 patients were analyzed (283 cT1/pT3, 237 cT2/pT2, 244 cT2/pT3, and 329 cT3/pT3). Median follow-up was 25.9 months. Cox regression demonstrated that cT2/pT3 (HR 2.7, p&lt;0.001 vs. cT1/pT3 [referent]) and cT3/pT3 (HR 2.6, p&lt;0.001 vs. cT1/pT3 [referent]) were significantly associated with worsened cancer specific mortality, while cT1/pT3 (HR 0.4, p&lt;0.001 vs. cT3/pT3 [referent]) and cT2/pT2 (HR 0.4, p&lt;0.001 vs. cT3/pT3 [referent]) were associated with improved cancer specific mortality. Based on this, we proposed to realign cT1/pT3 with cT2/pT2 and cT2/pT3 with cT3/pT3. KMA revealed significant differences in 5-year cancer specific survival (cT1/pT3 82%, cT2/pT2 81%, cT2/pT3 67%, and cT3/pT3 60%, p&lt;0.001). There were significant differences in 5-year overall survival (cT1/pT3 63%, cT2/pT2 67%, cT2/pT3 49%, and cT3/pT3 49%, p&lt;0.001), and 5-year recurrence free survival (cT1/pT3 80%, cT2/pT2 83%, cT2/pT3 70%, and cT3/pT3 59%, p&lt;0.001) on KMA. ROC analysis revealed an AUC of 0.529 for CSM and AUC of 0.502 for ACM using the current AJCC 8th edition TNM staging. ROC analysis revealed an AUC of 0.597 for CSM and AUC of 0.545 for our new proposal. Conclusions: Our analysis suggests that cT1 tumors pathologically upstaged to pT3 behave more similarly to pT2 tumors. Further delineation of pathologically upstaged tumors may more rationally stratify cancer specific survival outcomes to guide patient counseling and clinical decision making.

Oncologic outcomes in patients with residual invasive upper tract urothelial carcinoma following neoadjuvant chemotherapy.

475 Background: Emerging evidence supports use of neoadjuvant chemotherapy (NAC) prior to radical nephroureterectomy (RNU) for appropriately selected patients with upper tract urothelial carcinoma (UTUC). However, oncologic outcomes have not been well characterized for patients with residual muscle-invasive disease after NAC. Methods: We used a multi-institutional cohort from 24 centers in the U.S., Europe, and Japan to retrospectively identify patients who underwent RNU for UTUC from 1985-2022 and had high-grade muscle-invasive disease. We stratified the cohort based on receipt of NAC (&gt;ypT2 vs. &gt;pT2). Exclusion criteria included receipt of adjuvant chemotherapy, concurrent cystectomy with RNU, and distant metastatic disease. Baseline characteristics were compared between groups. Kaplan-Meier survival analysis with log-rank test was used to compare differences in recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS). Multivariable Cox regression and Fine-Gray competing risk regression were used to determine predictors of these outcomes. Results: A total of 1,233 patients were included, 62 of whom received NAC prior to RNU. A platinum-based regimen was used in 90% of NAC recipients, and the median number of cycles administered was 4 (IQR: 3-5). Median follow-up time among all patients was 22 months (IQR: 8-47 mo.). NAC recipients were more likely to have pathologic node positivity (35% vs. 13%) and less likely to have positive tumor margins (8% vs. 28%). On Kaplan-Meier analysis, NAC recipients with residual &gt;ypT2 disease had poorer outcomes than those with &gt;pT2 disease (2-year RFS [NAC vs. no NAC]: 52% vs. 80%, p&lt;0.001; 2-year OS: 60% vs. 78%, p=0.003; 2-year CSS: 61% vs. 86%, p&lt;0.001). Multivariable analyses also showed a statistically significant association between residual muscle-invasive disease after NAC and poorer RFS, OS, and CSS (Table). Conclusions: NAC recipients with &gt;ypT2 disease at RNU after exhibit poorer outcomes than stage-matched chemotherapy naïve counterparts. This may reflect effects of occult micrometastatic disease or chemoresistant primary tumors in non-responders. Our data highlight the need to improve prospective identification of candidates most likely to respond to NAC prior to RNU for UTUC in order to maximize its therapeutic benefit. [Table: see text]

National population-based survival estimates after definitive radiation therapy for prostate cancer.

395 Background: Understanding contemporary radiation therapy outcomes for prostate cancer (i.e., metastasis, death) is important for shared decision-making and setting expectations for patients and providers. Unfortunately, long-term outcome estimates are often derived from meta-analyses of outdated prospective clinical trials or population-based data lacking reliable clinical details (e.g., incident metastatic disease). For these reasons, we used a recently validated, natural language processing algorithm to identify incident metastatic prostate cancer within the electronic medical records of men treated with radiation therapy for localized prostate cancer in order to conduct an innovative and contemporary population-based survival outcomes study. Methods: We used national administrative, cancer registry, and electronic health record data for patients undergoing definitive radiation therapy with or without concurrent androgen deprivation therapy (ADT) within the Veterans Health Administration from 2005 to 2015. We used National Death Index data through 2019 for overall and prostate cancer-specific survival, and identified the date of incident metastatic prostate cancer using a validated natural language processing algorithm. We estimated metastasis-free, prostate cancer-specific, and overall survival using Kaplan-Meier methods. Results: We identified 41,876 patients treated with definitive radiation therapy for prostate cancer from 2005 through 2015, and followed them for over 8 years (follow up, median, 8.7 years, age at diagnosis, median, 65 years). Most patients had intermediate (42%) and high risk (33%) disease, with nearly half treated with ADT as part of initial therapy (44%). Unadjusted 10-year metastasis-free survival was 96%, 92%, and 80% for low, intermediate, and high risk disease. Similarly, unadjusted 10-year prostate cancer-specific survival was 98%, 97%, and 90% for low, intermediate, and high risk disease. Unadjusted overall survival was lower across disease risk categories at 77%, 71%, and 62% for low, intermediate, and high risk disease. Conclusions: These data provide population-based benchmarks for clinically relevant endpoints, including metastasis-free survival, among patients with low, intermediate, and high risk prostate cancer undergoing radiation therapy using contemporary techniques. The survival rates for high risk disease, in particular, compare favorably with historical outcomes.

Predictive factors for recurrence and outcomes in T1a renal cell carcinoma: Analysis of the INMARC (International Marker Consortium for Renal Cancer) database.

728 Background: Stage migration in renal cell carcinoma (RCC) has led to an increasing proportion of diagnoses at earlier clinical tumor stage and has rendered the phenomenon of the ‘small renal mass’ as a dominant presenting clinical paradigm. While thought of as being low risk, emerging knowledge about heterogeneity of RCC histologies and consequent impact on prognosis, in addition to awareness of impact of functional decline and demographic drivers on outcomes led us to further explore outcomes and predictive factors in T1a RCC patients treated with surgical resection. Methods: The INMARC database was queried for patients with small renal masses (≤ 4 cm) who underwent surgery via partial or radical nephrectomy and who presented without nodal or distant metastases. Patients were stratified into two groups based on having recurrence (distant or loco-regional) or not. Primary outcome was overall survival (OS). Multivariable analyses (MVA) were performed to analyze clinicopathological variables associated with recurrence and identify predictors of recurrence, cancer-specific mortality (CSM), and all-cause mortality (ACM). Kaplan-Meier analyses (KMA) were performed to compare recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) between histology types clear cell, chromophobe, papillary, and “other.” Results: We analyzed 1,878 cT1aN0M0 RCC patients; 101 (5.4%) developed recurrence (median follow up 53.6 months; median time to recurrence 19.3 months); 51.1% developed distant recurrence, 35.6% had loco-regional recurrence, and 13.9% experienced distant and loco-regional recurrence. MVA demonstrated age (HR=1.02, p=0.02), sex (HR=1.71, p=0.045), diabetes (HR=1.94, p=0.006), high/unclassified grade (HR=2.82-4.40, p&lt;0.001-0.007), papillary (HR=0.37, p=0.013) and other (HR=2.51, p=0.019) RCC as predictive factors for recurrence. MVA identified high/unclassified grade (HR=3.17-6.22, p=0.002-0.003) and papillary RCC (HR=0.12, p=0.036) as predictive factors for CSM. MVA for ACM demonstrated age (HR=1.03, p&lt;0.001), non-Caucasian race (HR=0.85, p&lt;0.001), high grade (HR=1.42, p=0.024), recurrence (HR=1.86, p=0.003), and GFR&lt;45 (HR=2.89, p&lt;0.001) to be independent risk factors. KMA comparing Clear Cell, Papillary, Chromophobe and Other RCC revealed significant differences for 5-year CSS (97.8% vs. 99.3% vs. 98.5% vs. 87.0%, p=0.018) and 5-year RFS (92.4% vs. 96.0% vs. 97.8% vs. 81.7%, p&lt;0.001), but not 5-year OS (89.4% vs. 85.2% vs. 93.2% vs. 73.7%, p=0.34). Conclusions: We noted differential outcomes in T1a RCC based on histology and grade for recurrence and CSM, while renal functional decline in addition to pathological factors and recurrence were predictive for ACM. These findings suggest consideration to refine management and post treatment surveillance strategies in T1a RCC.

Is pathological upstaging to T3a renal cell carcinoma associated with a similar prognosis to non-upstaged pathologic T3a disease? A multicenter analysis.

656 Background: Pathological upstaging to T3a disease may occur following radical (RN) or partial nephrectomy (PN) for patients with T1/T2 renal cell carcinoma (RCC). While a number of studies have demonstrated increased risk of T1/T2 upstaging to pT3a compared to initial staging, a comparison of pathologically upstaged T3a RCC and T3a RCC which was not upstaged has not been performed. We sought to compare survival outcomes and predictors of outcomes in patients who underwent surgical therapy for upstaged T3a RCC versus non-upstaged pT3a RCC. Methods: We conducted a retrospective analysis of a multi-institutional dataset of patients who underwent radical (RN) or partial nephrectomy (PN) with final pathologic stage of pT3a. Patients were classified as being upstaged (US) from cT1 or cT2 or non-upstaged (NUS) with cT3a disease. Primary outcome was Overall Survival (OS)/all-cause mortality (ACM). Secondary outcomes were Cancer-Specific Survival (CSS)/Cancer-Specific Mortality (CSM), and Recurrence-Free survival (PFS)/Recurrence. Multivariable Cox regression analysis (MVA) were conducted for predictors of mortality outcomes and Kaplan Meier Analyses (KMA) were conducted to elucidate survival outcomes comparing US and NUS groups. Results: We analyzed 879 patients [US 691 (cT1 389/cT2 302); NUS 188; median follow-up 48 months). NUS had significantly greater tumor size (9.3 vs. US 7.3 cm, p&lt;0.001), but no difference in positive surgical margins (6.9% vs. 3.9%, p=0.16). MVA for ACM revealed RN (HR 4.35, p&lt;0.001), clear-cell RCC (HR 2.38, p&lt;0.001), and positive surgical margin (HR 2.24, p=0.023) were independently associated, while upstaging status was not (p=0.78). MVA for CSM demonstrated age (HR 1.04, p=0.024) and positive margin (HR 5.28, p=0.029) were independently associated, while upstaging status was not (p=0.14). MVA for recurrence revealed positive margin (HR 6.7, p=0.003) and NUS (HR 3.85, p=0.001) to be associated with increased risk. KMA Comparing NUS and US groups, revealed no difference in 5-year OS (57% NUS vs. US 56%, p=0.38), and worsened 5-year CSS (NUS 66% vs. US 75%, p=0.04) and 5-year RFS (NUS 60% vs. US 84%, p&lt;0.001). Conclusions: Pathologic upstaging to T3a RCC was associated with a lower risk of recurrence compared to non-pathologically upstaged T3a RCC; nonetheless in our analysis upstaging status was not independently associated with increased risk of cancer-specific or overall mortality in T3a RCC. Our findings also highlight the importance of complete surgical resection in the setting of T3a disease and should prompt consideration of intensified follow up, aggressive re-salvage resection and use of adjuvant therapy.

Stenting as a bridge to surgery in obstructing colon cancer: Long-term recurrence pattern and competing risk of mortality.

Stenting as a bridge to curative surgery (SBTS) for obstructing colon cancer (OCC) has been associated with possibly worse oncological outcomes. To evaluate the recurrence patterns, survival outcomes, and colorectal cancer (CRC)-specific death in patients undergoing SBTS for OCC. Data from 62 patients undergoing SBTS at a single tertiary centre over ten years between 2007 and 2016 were retrospectively examined. Primary outcomes were recurrence patterns, overall survival (OS), cancer-specific survival (CSS), and CRC-specific death. OS and CSS were estimated using the Kaplan-Meier curves. Competing risk analysis with cumulative incidence function (CIF) was used to estimate CRC-specific mortality with other cause-specific death as a competing event. Fine-Gray regressions were performed to determine prognostic factors of CRC-specific death. Univariate and multivariate subdistribution hazard ratios and their corresponding Wald test P values were calculated. 28 patients (45.2%) developed metastases after a median period of 16 mo. Among the 18 patients with single-site metastases: Four had lung-only metastases (14.3%), four had liver-only metastases (14.3%), and 10 had peritoneum-only metastases (35.7%), while 10 patients had two or more sites of metastatic disease (35.7%). The peritoneum was the most prevalent (60.7%) site of metastatic involvement (17/28). The median follow-up duration was 46 mo. 26 (41.9%) of the 62 patients died, of which 16 (61.5%) were CRC-specific deaths and 10 (38.5%) were deaths owing to other causes. The 1-, 3-, and 5-year OS probabilities were 88%, 74%, and 59%; 1-, 3-, and 5-year CSS probabilities were 97%, 83%, and 67%. The highest CIF for CRC-specific death at 60 mo was liver-only recurrence (0.69). Liver-only recurrence, peritoneum-only recurrence, and two or more recurrence sites were predictive of CRC-specific death. The peritoneum was the most common metastatic site among patients undergoing SBTS. Liver-only recurrence, peritoneum-only recurrence, and two or more recurrence sites were predictors of CRC-specific death.

Prognostic nomogram for patients with tongue squamous cell carcinoma: A SEER-based study.

In order to predict the patients' prognosis with tongue squamous cell carcinoma (SCC), this study set out to develop a clinically useful and trustworthy prognostic nomogram. The Surveillance, Epidemiology, and End Results (SEER) Program was used to compile clinical information on patients with tongue SCC between 2010 and 2015. The likelihood of Cancer-Specific Survival (CSS) and Overall Survival (OS) for specific patients was predicted using a prognostic nomogram created with the help of the RStudio software. The nomogram's predictive ability was evaluated using the consistency index (C-index) and decision curve analysis, and the nomogram was calibrated for 1-, 2-, 3-, 5-, and 10-year CSS and OS. Patients numbering 6453were enrolled in this study. The primary cohort (3895) and validation cohort (2558) were each randomly assigned. Sex, age, tumor-node-metastasis (TNM) stage, surgery, chemotherapy, and radiation were significant risk factors for OS, whereas age, TNM stage, surgery, chemotherapy, and radiotherapy were significant risk factors for CSS. Additionally, C-index and calibration curves indicated that the prognostic nomogram prediction and the actual observation in both cohorts would be very coherent. The predictive nomogram created in this study can offer patients with tongue SCC customized treatment and survival risk assessment.

Common analgesics and ovarian cancer survival: the Ovarian cancer Prognosis And Lifestyle (OPAL) Study.

Most women with ovarian cancer (OC) are diagnosed with advanced disease. They often experience recurrence after primary treatment, and their subsequent prognosis is poor. Our goal was to evaluate the association between use of nonsteroidal antiinflammatory drugs (NSAIDs), including regular and low-dose aspirin, and 5-year cancer-specific survival after an OC diagnosis. The Ovarian cancer Prognosis And Lifestyle study is a prospective population-based cohort of 958 Australian women with OC. Information was gathered through self-completed questionnaires. We classified NSAID use during the year prediagnosis and postdiagnosis as none or occasional (<1 d/wk), infrequent (1-3 d/wk), and frequent (≥4 d/wk) use. We measured survival from the start of primary treatment: surgery or neoadjuvant chemotherapy for analyses of prediagnosis use, or 12 months after starting treatment (postdiagnosis use) until the earliest of date of death from OC (other deaths were censored) or last follow-up to 5 years. We used Cox proportional hazards regression to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) and applied inverse-probability of treatment weighting to minimize confounding. We also calculated restricted mean survival times. Compared with nonusers and infrequent users, we observed better survival associated with frequent NSAID use prediagnosis (HR = 0.73, 95% CI = 0.55 to 0.97) or postdiagnosis (HR = 0.65, 95% CI = 0.45 to 0.94). Estimates were similar for aspirin and nonaspirin NSAIDs, new and continuous users and in weighted models. These differences would translate to a 2.5-month increase in mean survival by 5 years postdiagnosis. There was no association with acetaminophen. Our findings confirm a previous study suggesting NSAID use might improve OC survival.

Prognostic value of the sarcomatoid component in bladder cancer: A propensity score matching study.

Sarcomatoid carcinoma of the bladder is rare, and little is known about the prognostic impact of the proportion of sarcomatoid components of the bladder. The present study aimed to assess the prognostic value of the proportion of sarcomatoid components with regard to death and recurrence rates in patients with bladder cancer (BC), and to validate the worse survival results of sarcomatoid carcinomas of the bladder using propensity score matching. Patients with sarcomatoid carcinoma of the bladder who were treated at the Affiliated Hospital of Qingdao University between August 2010 and May 2021 were included in the study. A 1:2 propensity score matching system based on age, sex and pathological T stage was used for sarcomatoid and non-sarcomatoid carcinoma matching. Finally, 114 patients with BC were included. Patients with sarcomatoid carcinoma had worse 5-year cancer-specific survival (CSS) (69.1 vs. 86.9%; log-rank P=0.008) and recurrence-free survival (RFS) (64.1 vs. 83.6%; log-rank P=0.001) rates compared with patients with non-sarcomatoid carcinoma, as had the subgroup with muscle invasion. Multivariate analysis revealed sarcomatoid carcinoma as an independent prognostic factor. Patients with a low proportion of sarcomatoid components (1-50%) had a better prognosis than patients with a high proportion (>50%), and no significant difference was found compared with the non-sarcomatoid group. Overall, a proportion of sarcomatoid components >50% was a predictor of CSS and RFS. Sarcomatoid components markedly increased the risk of death and recurrence in muscle-invasive BC, but not in non-muscle-invasive BC. A higher proportion of sarcomatoid components was significantly associated with poorer survival.

Thermal ablation vs. active surveillance for renal masses: a systematic review and network meta-analysis.

Partial nephrectomy, thermal ablation and active surveillance are acceptable options for T1 stage renal tumor management. Currently, we lack sufficient information to make an accurate comparison of thermal ablation with active surveillance. The study objectives were to compare thermal ablation with active surveillance indirectly using partial nephrectomy as a reference. We performed a systematic literature search using two databases (Scopus and Medline). The detailed search strategy is available at Prospero, CRD42021290055. The primary outcome was cancer-specific survival. Secondary outcomes included overall survival and metastasis-free survival. The final sample comprised 33 articles. They included the ones that compare: partial nephrectomy to ablation (29 studies), partial nephrectomy to active surveillance (2 studies), and partial nephrectomy vs. active surveillance vs. ablation (2 articles). We assessed 3-year and 5-year cancer-specific survival, and 3-, 5- and 7-year overall survival. The surface under the cumulative ranking curve (SUCRA) treatment benefit ranking was: cancer-specific survival - 48.6% for thermal ablation and 1.6% for active surveillance (5-year follow-up); overall survival - 52% for thermal ablation and 0.6% for active surveillance (7-year follow-up). The results demonstrated a significantly higher 3-year cancer-specific survival (RR 1.55, P=0.02) and 3- and 7-year follow-up overall survival (RR 1.85, P=0.03) in thermal ablation compared to active surveillance. At 5-year follow-up, cancer-specific survival and overall survival were in favor of thermal ablation while no statistically significant difference was reported. Thermal ablation offers a significantly higher cancer-specific survival and overall survival at mid-term follow-up in the management of T1 renal tumors compared to active surveillance. However, it is necessary to conduct further prospective randomized studies to validate the data.

The association between KRAS mutational status, clinicopathological factors including the preoperative systemic inflammatory response and outcomes in TNM stage I-III colon cancer.

193 Background: TNM Stage is the most significant prognostic indicator in colon cancer however other tumour and host factors (eg the systemic inflammatory response (SIR)) are associated with long-term outcomes. The relationship between the tumour and the host SIR remains poorly understood. KRAS mutations are associated with adverse outcomes in metastatic disease and have been reported to have an inflammatory phenotype however this has not been widely studied in non-metastatic disease. The present study investigates the association between KRAS mutations, clinicopathological factors including the SIR and outcomes in TNM I-III colon cancer. Methods: Two cohorts of patients (single centre–2000-2008 and regional-2011-2014) undergoing curative surgery for TNM I-III colon cancer in the West of Scotland were shown to be well-matched and combined. Mutational status was analysed retrospectively. The SIR was stratified using Systemic Inflammatory Grade (SIG). 3-year overall and cancer specific survival (OS and CSS) were measured from date of surgery until date of death. Results: 267 patients were identified, 45% with KRAS mutations. KRAS mutations were associated with: right sided (p=0.013), well differentiated (p=0.011), BRAF-wt (p&lt;0.001), PIK3CA-wt (p=0.027) and P53-wt (p=0.002) tumours. A trend was seen between KRAS mutations and female sex (p=0.074) and increased SIG (p=0.072). No association was seen with age, deprivation, smoking, ASA Grade, TNM Stage or EMVI. KRAS mutant status was associated with adverse 3-year CSS (74% versus 82%, p=0.006) and OS (69% versus 78%, p=0.070). For CSS, TNM Stage (HR 2.92, p&lt;0.001), KRAS mutant status (HR 1.64, p=0.050) and Systemic Inflammatory Grade (HR 1.34, p=0.004) were independently prognostic. For OS: age (HR 1.39, p=0.022), TNM Stage (HR 1.50, p=0.016) and SIG (HR 1.25, p=0.005) were independently prognostic. A trend was seen between KRAS mutant status and adverse OS (HR 1.47, p=0.079). Conclusions: The present results show an association between KRAS mutational status and SIG. Furthermore, both of these factors were associated with adverse oncological outcomes. Further investigation into the association between KRAS-mutant status and the local/systemic inflammatory response in TNM I-III colon cancer is warranted. While comprehensive genomic profiling is likely to become increasingly common place, staging the host (SIR) should also be routinely undertaken.

A nomogram and risk classification system forecasting the cancer-specific survival of lymph- node- positive rectal cancer patient after radical proctectomy.

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. 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. 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). 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.

P412 Time trend in clinicopathological features and prognosis of Ulcerative Colitis associated neoplasia: A nationwide cohort in Japan

Abstract Background With an increase in the number of Ulcerative Colitis (UC) patients in Japan, UC associated neoplasia (UCAN) cases have been accumulated. Laparoscopic surgery for sporadic advanced colorectal cancer was approved in 2002 and biologic agents have been approved for UC from 2010 in Japan. However, few reports have ever examined the time trend using a large patient cohort. We aimed to clarify time trend in clinicopathological features and prognosis of UCAN with a nationwide cohort. This study was conducted as a sub-analysis of the nationwide retrospective study across 47 institutions from the Japanese Society for Cancer of the Colon and Rectum. Methods A total of 1,139 UCAN patients were identified in the nationwide cohort from 1983 to 2020. Clinicopathological features, 5-year cancer specific survival (CSS) and overall survival (OS) were compared among the following three groups by the period of UCAN diagnosis, before 2000, 2001-2010 and 2011-2020 (the results are shown in this order). Results The number of UCAN patients registered in the database were 59, 340 and 740 in each period. Age at UCAN diagnosis (47, 51, 54, median, p&amp;lt;0.01) and the disease duration from UC diagnosis to UCAN diagnosis (14.3, 16.0, 17.5 years, mean, p&amp;lt;0.01) increased through the study periods. The rate of a surveillance colonoscopy as a diagnostic procedure (36.2%, 58.6%, 72.8%, p&amp;lt;0.01) increased without a change in the ratios of early (pathological stage 0-I) neoplasia (60.7%, 59.5%, 62.2%, p=0.72). Laparoscopic surgery became a dominant surgical procedure in the recent cases (1.7%, 33.2%, 47.7%, p&amp;lt;0.01) without an increase in postoperative complication rate (39.7%, 29.2%, 29.8%, p=0.26). Improvement in 5-year CSS (77.2%, 87.5%, 90.7%, p&amp;lt;0.05) and OS (77.2%, 84.3%, 88.5%, p&amp;lt;0.05) was observed. Among pathological stage III patients, better curative resection rate (66.7%, 92.6%, 97.1%, p&amp;lt;0.01) and the more use of adjuvant chemotherapy in the last decade (50.0%, 58.5%, 76.6%, p&amp;lt;0.05) were observed. Conclusion Longer duration of UC before the diagnosis of UCAN was observed in recent cases, which might be due to the improvement of medical therapy, including biologic agents. Minimally invasive surgery prevailed without an increase in postoperative complications. Curative resection and adjuvant chemotherapy might play a role in improvement of 5-year CSS and OS.

Colorectal cancer in young patients below screening age – Demographic and socioeconomic factors associated with incidence and survival

BackgroundWhile early onset colorectal cancer (EOCRC) has previously been defined as CRC in patients younger than age 50, recent screening guidelines have been lowered to 45. With more younger patients aged 45–50 are now being screened, incidence trend and outcomes of very early EOCRC (20–44) remains unclear. MethodSurveillance, Epidemiology, and End Results database was analyzed between 2006 and 2016 using Joinpoint tool to evaluate annual percentage change (APC) in incident rates, focusing on race/ethnicity and socioeconomic status (SES). Cancer specific survival (CSS) was assessed using univariate and multivariate analysis. Results41,815 EOCRC patients met inclusion criteria. Incidence has increased significantly in both age groups (APC in age group 20–44 = 1.21 and 45–49 = 1.06). Increase incidence of very early EOCRC was observed in White and Hispanic racial/ethnic groups (ACP 1.68 and 2.63), as well as population from counties with high poverty, unemployment, language barrier, foreign born resident, and high school dropout rates (ACP 2.07, 1.87, 1.21, 1.28 and 2.02 respectively). Further, the 5-year CSS was worse in Black patients, and patients from counties with high poverty, unemployment and high school dropouts rates (Age group 20–44, 63.11%, 66.39%, 67.48% and 66.95% respectively). On multivariate analysis, living in high poverty counties was an independent risk factor for poorer CSS for very early EOCRC (HR 1.20, 95% CI 1.07–1.34, p = 0.002). Multivariate analysis was adjusted by sex, pathology type, site of disease, disease extension and surgical treatment history. ConclusionVery early EOCRC incidence increases in White, Hispanic and poor patients, and outcomes are worse for minority and low-income patients. Further study on very early EOCRC is needed among those patients.

Prognostic significance and risk factors for pelvic and para-aortic lymph node metastasis in type I and type II ovarian cancer: a large population-based database analysis

BackgroundTo compare the prognosis of lymphatic metastasis in type I and type II epithelial ovarian cancer (OC) and to identify the risk factors for pelvic lymph node metastases (PLNs) and para-aortic lymph node metastases (PALNs).MethodsPatients diagnosed with epithelial OC were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and cancer-specific survival (CSS) were estimated. The Cox proportional hazards regression model was used to identify independent predictors of survival.ResultsA total of 11,275 patients with OC were enrolled, including 31.2% with type I and 68.8% with type II. Type II and high tumour stage were risk factors for lymph node involvement (p < 0.05). The overall rate of lymph node metastasis in type I was 11.8%, and that in type II was 36.7%. In the type I group, the lymph node metastasis rates in stages T1, T2, T3 and TXM1 were 3.2%, 14.5%, 40.4% and 50.0%, respectively. In the type II group, these rates were 6.4%, 20.4%, 54.1% and 61.1%, respectively. Age and tumour size had little effect on lymph node metastasis, and grade 3 was not always a risk factor. For the type I group, the 10-year CSS rates of LN(-), PLN( +), PALN( +), and PLN + PALN( +) were 80.6%, 46.6%, 36.3%, and 32.3%, respectively. The prognosis of PLN ( +) was better than that of PALN ( +) in the type I group (p > 0.05). For the type II group, the 10-year CSS rates of LN(-), PLN( +), PALN( +), and PLN + PALN( +) were 55.6%, 18.5%, 25.7%, and 18.2%, respectively. PALN ( +) had a significantly better prognosis than PLN ( +) in the type II group (p < 0.05).ConclusionsThe clinical characteristics and prognoses of patients with type I and type II OC differed greatly. Patients with type II and higher tumour stages had poorer prognoses. Type I with PALN metastasis and type II with PLN metastasis indicated a worse prognosis. Patients with stage TI did not require lymph node dissection, especially in the type I group.

Clinicopathological and Treatment Patterns of Combined Small-Cell Lung Carcinoma with Future Insight to Treatment: A Population-Based Study.

Primary lung cancer is the most common cause of cancer-related mortality in the United States (US). Approximately 90% of lung cancers are associated with smoking and the use of other tobacco products. Based on histology, lung cancers are divided into small-cell lung carcinomas (SCLCs) and non-small-cell lung carcinomas (NSCLCs). Most SCLCs are of the pure subtype, while the rare combined SCLCs contain elements of both small-cell and non-small-cell morphologies. This study sought to evaluate the demographics, clinical factors, molecular abnormalities, treatment approaches, and survival outcomes with combined SCLC and NSCLCs. Data on 2126 combined SCLC patients was extracted from the Surveillance Epidemiology and End Result (SEER) database from 2000 to 2018. Data extracted for analyses included age, sex, race, tumor size, tumor location, metastasis status, stage at diagnosis, treatment received, and treatment outcomes. Multivariate analysis was performed using Statistical Product and Service Solutions (SPSS) software. The patients had a median age of 68 years; 43.9% of the patients were female and 56.1% were male; 84.5% were White and 11.7% were African Americans. The majority of patients had a poorly differentiated disease at 29.6%; 17% were undifferentiated, 3.2% were moderately differentiated, and 0.8% were well differentiated. Chemotherapy was the most common treatment modality (45.3%); 17% underwent surgery only, 10.3% underwent surgery followed by adjuvant chemotherapy, and 10% underwent radiation after surgery. Five-year cancer-specific survival was 15.2% with surgery alone, and combined surgery and chemotherapy provided the highest percentages (38.3% and 34.7%, respectively). Females had significantly higher 1- and 5-year cancer-specific survival rates compared to males (59.3% and 29.9% vs. 48.0% and 23.7, respectively; p < 0.001). Well-differentiated tumors had significantly higher survival compared to other gradings (p < 0.001). Survival decreased as tumor staging moved distally from localized to regional to distant (p < 0.001). Metastasis to bone, liver, brain, and lung significantly decreased survival in comparison to patients who did not have any metastasis (p < 0.001). Females had significantly shorter survival compared to their counterparts when metastasis was to the bone, brain, or liver (p < 0.001). Multivariate analysis identified male sex (Hazard Ratio (HR) = 1.2), undifferentiated grade (HR = 1.9), regional extent of disease (HR = 1.7), distant extent of disease (HR = 3.7), and metastasis to liver (HR = 3.5) as variables associated with worse survival. Combined SCLC is overall very rare. However, the frequency of presentation with combined SCLC is on the rise, in part due to improvements in diagnostic techniques. Despite advances in therapies, treating combined SCLC is challenging, and novel therapies are not utilized, owing to low rates of targetable mutations. Combined SCLC has higher survival rates if well differentiated.