Current and future cancer staging after neoadjuvant treatment for solid tumors.

Until recently, cancer registries have only collected cancer clinical stage at diagnosis, before any therapy, and pathological stage after surgical resection, provided no treatment has been given before the surgery, but they have not collected stage data after neoadjuvant therapy (NAT). Because NAT is increasingly being used to treat a variety of tumors, it has become important to make the distinction between both the clinical and the pathological assessment without NAT and the assessment after NAT to avoid any misunderstanding of the significance of the clinical and pathological findings. It also is important that cancer registries collect data after NAT to assess response and effectiveness of this treatment approach on a population basis. The prefix y is used to denote stage after NAT. Currently, cancer registries of the American College of Surgeons' Commission on Cancer only partially collect y stage data, and data on the clinical response to NAT (yc or posttherapy clinical information) are not collected or recorded in a standardized fashion. In addition to NAT, nonoperative management after radiation and chemotherapy is being used with increasing frequency in rectal cancer and may be expanded to other treatment sites. Using examples from breast, rectal, and esophageal cancers, the pathological and imaging changes seen after NAT are reviewed to demonstrate appropriate staging.

Enhancing Preoperative Diagnosis Accuracy of Stage III Gastric Cancer with Circulating circRNAs.

BACKGROUND: The prognosis remains poor for stage III gastric cancer, and neoadjuvant chemotherapy is increasingly used to improve outcomes. Accurate diagnosis prior to treatment is essential to develop appropriate treatment strategies for poor prognosis subgroups. This study aims to enhance the accuracy of pre-treatment gastric cancer diagnosis using a biological approach centered on circulating circular RNA (circRNA). MATERIALS AND METHODS: We conducted a comprehensive analysis of circRNA expression profiles using two Gene Expression Omnibus datasets to identify circRNA candidates associated with stage III gastric cancer. Subsequently, we validated these circRNA biomarkers in two independent clinical cohorts comprising a total of 174 patients with gastric cancer and non-disease controls through real-time polymerase chain reaction (PCR). RESULTS: Genome-wide circRNA analysis identified a panel of four biomarkers capable of diagnosing pathologically confirmed stage III (pStage III) gastric cancer. In a training cohort (n = 83), a clinically applicable panel of four circRNAs was developed (AUC 0.81), which was successfully validated in an independent clinical cohort (n = 82; AUC 0.76). To assess clinical utility, we combined clinical imaging (cStage) with the circRNA panel. Among those initially diagnosed as cStage III but later confirmed as pStage I/II, 86% were accurately diagnosed using the molecular biological approach with circRNAs. CONCLUSIONS: We have developed a circRNA-based non-invasive liquid biopsy that can improve the diagnostic performance of pStage III gastric cancer before treatment. Our circRNA model could provide a sophisticated and personalized approach to assist in treatment planning for patients with advanced gastric cancer.

Gross Hematuria Does not Affect the Selection of Nephrectomy Types for Clinical Stage 1 Clear Cell Renal Cell Carcinoma: A Multicenter, Retrospective Cohort Study.

PURPOSE: This study aimed to discuss the correlation between gross hematuria and postoperative upstaging (from T1 to T3a) in patients with cT1 clear cell renal cell carcinoma (ccRCC) and to compare oncologic outcomes of partial nephrectomy (PN) and radical nephrectomy (RN) in patients with gross hematuria. METHODS: A total of 2145 patients who met the criteria were enrolled in the study (including 363 patients with gross hematuria). The least absolute selection and shrinkage operator logistic regression was used to evaluate the risk factor of postoperative pathological upstaging. The propensity score matching (PSM) and stable inverse probability of treatment weighting (IPTW) analysis were used to balance the confounding factors. The Kaplan-Meier analysis and multivariate Cox proportional risk regression model were used to assess the prognosis. RESULTS: Gross hematuria was a risk factor of postoperative pathological upstaging (odds ratio [OR] = 3.96; 95% confidence interval [CI] 2.44-6.42; P < 0.001). After PSM and stable IPTW adjustment, the characteristics were similar in corresponding patients in the PN and RN groups. In the PSM cohort, PN did not have a statistically significant impact on recurrence-free survival (hazard ratio [HR] = 1.48; 95% CI 0.25-8.88; P = 0.67), metastasis-free survival (HR = 1.24; 95% CI 0.33-4.66; P = 0.75), and overall survival (HR = 1.46; 95% CI 0.31-6.73; P = 0.63) compared with RN. The results were confirmed in sensitivity analyses. CONCLUSIONS: Although gross hematuria was associated with postoperative pathological upstaging in patients with cT1 ccRCC, PN should still be the preferred treatment for such patients.

Inaccurate Clinical Stage Is Common and Associated With Poor Survival in Patients With Lung Cancer.

INTRODUCTION: Clinical staging in lung cancer has implications for treatment planning and prognosis. We sought to determine the rate of inaccurate clinical stage (relative to pathologic), identify risk factors for inaccuracy, and evaluate the association of inaccuracy on survival. We hypothesized that inaccurate staging was associated with poor survival. METHODS: In this retrospective cohort study, adult patients who received surgical resection without neoadjuvant treatment for nonsmall cell lung cancer from 2004 to 2020 in the National Cancer Database were categorized by accuracy of clinical stage (relative to pathologic stage). Multivariate models were used to determine risk factors for inaccuracy. The association between inaccuracy and overall survival was also analyzed. RESULTS: We identified 255,598 patients with lung cancer, including 84,543 patients (33.1%) who were inaccurately staged. Stage inaccuracy was associated with higher tumor, node, metastasis stage (T-category 3: odds ratio [OR] = 1.2, 95% confidence interval [CI] 1.15-1.28; N-category 2: OR = 2.6, 95% CI 2.47-2.79), greater quantity of lymph nodes evaluated, and more extensive resection (extended lobectomy/bilobectomy: OR = 1.3, 95% CI 1.20-1.37; pneumonectomy: OR = 1.6, 95% CI 1.54-1.74). Patients undergoing robotic surgery were less likely to be inaccurately staged (OR = 0.89, 95% CI 0.852-0.939). Inaccurate staging was associated with worse overall survival (5-y 67.5% accurate versus 55.4% inaccurate, P < 0.001). Inaccurate staging was also associated with worse survival in a multivariate Cox model (hazard ratio [HR] = 1.3, 95% CI 1.29-1.33). Both "understaging" (path > clinical) and "overstaging" (clinical > path) were associated with inferior survival. CONCLUSIONS: Inaccurate clinical stage (relative to pathologic) occurs in one-third of patients receiving surgery for lung cancer. Inaccuracy is associated with poor survival. Quality improvement initiatives should focus on improving clinical staging accuracy.

Transition of adolescents living with HIV from pediatric to adult care, a retrospective 12-year Single Center Study from the Sahel Region in West-Africa.

ABSTRACTTransition is the next major hurdle in the field of HIV-infected youth, especially in sub-Saharan Africa. At St Camille Hospital in Ouagadougou, fully informed and compliant patients over 13-years-old were eligible for referral to the adult HIV/AIDS service, after completion of an individualized preparatory process. Transition consisted in at least two consecutive "joined-service" appointments in the respective facilities. We retrospectively compared immunological, clinical, and therapeutical data one year before transition, at transition and one year after transition. Between 2008 and 2019 73 patients (34 females, 39 males) were transitioned. All had been previously in pediatric care for at least 1 year and 66 were on HAART. Matched paired analysis of CD4 counts revealed a modest drop in CD4 cells over time (p < 0.05). Clinical data also showed strong fluctuation between WHO clinical stages over the three time points, with a clear trend towards increased severity especially post transfer. This large retrospective 12-year single-center experience from a Sahel country showed a 95.8% retention rate at one year. It demonstrates how a comprehensive plan, carefully implemented, can provide excellent retention, even in a low-resource setting. However, mild immunological decline was associated with a worrisome clinical deterioration, underlining the importance of assessing the latter after transition.

Systematic DOE Approach for Dry Granulation Study at Early Clinical Stage of Novel Drugs: An Industrial Case.

In order to introduce a cost-effective strategy method for commercial scale dry granulation at the early clinical stage of drug product development, we developed dry granulation process using formulation without API, fitted and optimized the process parameters adopted Design of Experiment (DOE). Then, the process parameters were confirmed using one formulation containing active pharmaceutical ingredient (API). The results showed that the roller pressure had significant effect on particle ratio (retained up to #60 mesh screen), bulk density and tapped density. The roller gap had significant influence on particle ratio and specific energy. The particle ratio was significantly affected by the mill speed (second level). The tabletability of the powder decreased after dry granulation. The effect of magnesium stearate on the tabletability was significant. In the process validation study, the properties of the prepared granules met the requirements for each response studied in the DOE. The prepared tablets showed higher tensile strength, good content uniformity of filled capsules, and the dissolution profiles of which were consistent with that of clinical products. This drug product process development and research strategies could be used as a preliminary experiment for the dry granulation process in the early clinical stage.

Does stage III rectal mucinous adenocarcinoma benefit from neoadjuvant chemoradiation?

BACKGROUND: This study aimed to compare clinical outcomes of patients with clinical stage III mucinous rectal adenocarcinoma (M) and non-mucinous rectal adenocarcinoma (NM) and evaluate the effectiveness of neoadjuvant chemoradiation. It was hypothesized that patients with M would fare worse with neoadjuvant chemoradiation than those with NM and that patients with M and NM not receiving chemoradiation would have similar outcomes. Moreover, it was hypothesized that patients with M would have similar outcomes regardless of chemoradiation. METHODS: This study compares eligible patients distributed in three cohorts: (cohort 1) M versus NM, including only patients treated with neoadjuvant chemoradiation; (cohort 2) M versus NM, including only patients treated without neoadjuvant chemoradiation; and (cohort 3) only M patients treated with versus without neoadjuvant chemoradiation. RESULTS: We identified 515 patients with an average age of 58.8 (SD 12.4) years, and 30% were female. Fifty-seven (11.1%) patients had M and 458 (88.9%) had NM. Neoadjuvant chemoradiation was administered to 382 (74%) patients, of whom 41 (10.7%) were M and 341 (89.3%) NM. In cohort 1, patients with M had advanced pathological staging (stage 3: M 68% vs. NM 42%; p < 0.001), worse pathological differentiation (poor: M, 37% vs. NM, 11%; p = 0.001), more involved lymph nodes (M 0 [0;7] vs. NM 0 [0;1]; p < 0.001) and a higher rate of local recurrence (M 22% vs. 3%; p < 0.001). Patients with M demonstrated worse 7-year cancer-specific (p = 0.007) and overall survival (p = 0.01). There were no significant differences in cohort 2 and 3. CONCLUSION: Patients with clinical stage III mucinous adenocarcinomas may not benefit as much from standard neoadjuvant chemoradiation as their non-mucinous counterparts do.

Excellent survival in relapsed stage I testicular cancer.

BACKGROUND: Two thirds of patients with germ-cell cancer (GCC) present as clinical stage I (CSI). Following orchiectomy, active surveillance (AS) has become their standard management. However, 15-50% of patients eventually relapse with metastatic disease after AS. Relapses need to be detected early in order to achieve cure and avoid overtreatment. METHODS: We retrospectively analyzed consecutive GCC patients treated at two Swiss academic centers between 2010 and 2020. Patients with stage IS and extragonadal primaries were excluded. We compared disease characteristics and survival outcomes of patients relapsed from initial CSI to patients with de novo metastatic disease. Primary endpoint was the IGCCCG category at the time of relapse. Main secondary endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: We identified 360 GCC patients with initial CSI and 245 de novo metastatic patients. After a median follow-up of 47 months, 81 of 360 (22.5%) CSI patients relapsed: 41 seminoma (Sem) and 40 non-seminoma (NSem) patients. All Sems relapsed in the IGCCCG good prognosis group. NSem relapsed with good 29/40 (72.5%) and intermediate 11/40 (27.5%) prognostic features; 95.1% of relapses occurred within five years post-orchiectomy. Only 3 relapsed NSem patients died from metastatic disease. Five-year OS for relapsed CSI patients was 100% for Sem and 87% (95% CI: 61-96%) for NSem patients; five-year PFS was 92% (95% CI: 77-97) and 78% (95% CI: 56-90) for Sem and NSem, respectively. When stratified by IGCCCG prognostic groups, good risk relapsed patients had a trend towards better OS and PFS as compared to de novo metastatic patients. CONCLUSIONS: GCC patients who relapse after initial CSI can be detected early by active surveillance and have an excellent survival.

Association of wound, ischemia, and foot infection clinical stage with frailty and malnutrition in chronic limb-threatening ischemia patients undergoing endovascular intervention.

OBJECTIVE: The Wound, Ischemia, and foot Infection (WIfI) clinical stage has been thought to have a prognostic value in Chronic limb-threatening ischemia (CLTI) patients, and frailty and nutritional status appear to represent pivotal factor affecting prognosis among CLTI patients. The purpose of this study was to examine clinical factors (including frailty and nutritional status) relevant to WIfI clinical stage. METHODS: This retrospective study investigated 200 consecutive CLTI patients. We individually assessed WIfI clinical stage, frailty according to the Clinical Frailty Scale (CFS) score, and malnutrition according to Geriatric Nutritional Risk Index (GNRI). We then compared mortality after endovascular intervention between a WIfI stage 1, 2 group and a stage 3, 4 group, and investigated associations between baseline characteristics (including CFS and GNRI) and WIfI clinical stage. RESULTS: Among 200 patients, 123 patients (62%) showed WIfI stage 1 or 2, and the remaining 77 patients (38%) had WIfI stage 3 or 4. CFS score was significantly higher in the WIfI stage 3, 4 group [median 6.0, interquartile range (IQR) 5.5-7.0] compared with the WIfI stage 1, 2 group (median 5.0, IQR 4.0-6.0, p < 0.001), and GNRI was significantly lower in the WIfI stage 3, 4 group (median 88, IQR 80-97) than in the WIfI stage 1, 2 (median 103, IQR 94-111, p < 0.001). Forty patients (20%) died after endovascular intervention. Incidences of all-cause and cardiac deaths were higher in the WIfI stage 3, 4 group than in the WIfI stage 1, 2 group (27% vs. 15%, p = 0.047 and 12% vs. 3%, p = 0.040, respectively). Kaplan-Meier analysis showed a significantly lower survival rate in the WIfI stage 3, 4 group than in the WIfI stage 1, 2 group (p = 0.002 by log-rank test). Multivariate logistic regression analysis using relevant factors from univariate analysis showed CFS score [odds ratio (OR) 2.06, 95% confidence interval (CI) 1.41-3.13, p < 0.001), diabetes mellitus (OR 3.17, 95%CI 1.17-8.61, p = 0.023) and GNRI (OR 0.93, 95%CI 0.89-0.97, p = 0.002) significantly associated with WIfI stage 3 or 4. In addition, multivariate ordinal logistic regression analysis for WIfI clinical stage showed CFS score (OR 1.43, 95%CI 1.09-1.89, p = 0.011), diabetes mellitus (OR 1.77, 95%CI 1.26-2.54, p < 0.001), and high-sensitivity C-reactive protein (OR 1.14, 95%CI 1.02-1.28, p = 0.041) were positively associated with WIfI clinical stage, and GNRI correlated negatively with WIfI clinical stage (OR 0.95, 95%CI 0.91-0.97, p < 0.001). CONCLUSIONS: These results indicate that CLTI patients with high WIfI clinical stage may be more frail and malnourished, and be associated with poor prognosis after endovascular intervention.

Classification of Histological Types and Stages in Non-small Cell Lung Cancer Using Radiomic Features Based on CT Images.

Non-invasive diagnostic method based on radiomic features in patients with non-small cell lung cancer (NSCLC) has attracted attention. This study aimed to develop a CT image-based model for both histological typing and clinical staging of patients with NSCLC. A total of 309 NSCLC patients with 537 CT series from The Cancer Imaging Archive (TCIA) database were included in this study. All patients were randomly divided into the training set (247 patients, 425 CT series) and testing set (62 patients, 112 CT series). A total of 107 radiomic features were extracted. Four classifiers including random forest, XGBoost, support vector machine, and logistic regression were used to construct the classification model. The classification model had two output layers: histological type (adenocarcinoma, squamous cell carcinoma, and large cell) and clinical stage (I, II, and III) of NSCLC patients. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with 95% confidence interval (CI) were utilized to evaluate the performance of the model. Seven features were selected for inclusion in the classification model. The random forest model had the best classification ability compared with other classifiers. The AUC of the RF model for histological typing and clinical staging of NSCLC patients in the testing set was 0.700 (95% CI, 0.641-0.759) and 0.881 (95% CI, 0.842-0.920), respectively. The CT image-based radiomic feature model had good classification ability for both histological typing and clinical staging of patients with NSCLC.

Oral Squamous Cell Carcinoma Clinico-pathological features in relation to Tumor Stage; AJCC 2018 perspective.

Objective: To investigate the association between clinicopathological findings and tumor stage according to AJCC 2018 guidelines in patients suffering from Oral squamous cell carcinoma (OSCC). Methods: A descriptive study was conducted from January 2019 to January 2020 at King Edward Medical University and University of Health Sciences on a total of 49 patients enrolled after obtaining written informed consent. Clinical and radiographic findings were recorded. Pathological reporting was done using AJCC 2018 cancer staging guidelines. Association between clinicopathological features with tumor stage and grade was assessed using Chi-square and Kruskal-Wallis test. Result: Mean age of the patients was 46.1 ± 10.6 years. Most of the tumors were of well differentiated type (49%) and moderately differentiated (40.8%) with predominant clinical stage III in 42.9% & IV in 44.9 % and primary tumor stage pT2 28.6% & pT3 36.7%. Significant difference was seen for primary tumor stage in relation to age, gender, depth of invasion, primary site, and size of tumor (p < 0.01). For clinical stages, significant difference was observed in the age, gender, size of tumor, nodal metastasis, and anatomical tumor site (p < 0.01). Conclusion: Application of 8th Edition AJCC guidelines identifies the importance of the latest classification with strong association of latest stage criteria with age, gender, site of primary tumor, tumor thickness, depth of invasion, nodal metastasis and size of largest lymph node involved, and Level of Lymph node involved (level III & V) in a subset of patients from a developing country.

Clinical staging and the differential risks for clinical and functional outcomes in young people presenting for youth mental health care.

BACKGROUND: Clinical staging proposes that youth-onset mental disorders develop progressively, and that active treatment of earlier stages should prevent progression to more severe disorders. This retrospective cohort study examined the longitudinal relationships between clinical stages and multiple clinical and functional outcomes within the first 12 months of care. METHODS: Demographic and clinical information of 2901 young people who accessed mental health care at age 12-25 years was collected at predetermined timepoints (baseline, 3 months, 6 months, 12 months). Initial clinical stage was used to define three fixed groups for analyses (stage 1a: 'non-specific anxious or depressive symptoms', 1b: 'attenuated mood or psychotic syndromes', 2+: 'full-threshold mood or psychotic syndromes'). Logistic regression models, which controlled for age and follow-up time, were used to compare clinical and functional outcomes (role and social function, suicidal ideation, alcohol and substance misuse, physical health comorbidity, circadian disturbances) between staging groups within the initial 12 months of care. RESULTS: Of the entire cohort, 2093 young people aged 12-25 years were followed up at least once over the first 12 months of care, with 60.4% female and a baseline mean age of 18.16 years. Longitudinally, young people at stage 2+ were more likely to develop circadian disturbances (odds ratio [OR]=2.58; CI 1.60-4.17), compared with individuals at stage 1b. Additionally, stage 1b individuals were more likely to become disengaged from education/employment (OR=2.11, CI 1.36-3.28), develop suicidal ideations (OR=1.92; CI 1.30-2.84) and circadian disturbances (OR=1.94, CI 1.31-2.86), compared to stage 1a. By contrast, we found no relationship between clinical stage and the emergence of alcohol or substance misuse and physical comorbidity. CONCLUSIONS: The differential rates of emergence of poor clinical and functional outcomes between early versus late clinical stages support the clinical staging model's assumptions about illness trajectories for mood and psychotic syndromes. The greater risk of progression to poor outcomes in those who present with more severe syndromes may be used to guide specific intervention packages.

SLC4A4 promotes prostate cancer progression in vivo and in vitro via AKT-mediated signalling pathway.

BACKGROUND: Prostate cancer (PCa) is the second leading cause of cancer-related male deaths worldwide. The purpose of this study was to investigate the effects of homo sapiens solute carrier family 4 member 4 (SLC4A4), which encodes the electrogenic Na+/HCO3- cotransporter isoform 1 (NBCe1), in the development and progression of PCa. METHODS: The expression levels of SLC4A4 in PCa and normal prostate tissues were evaluated by immunohistochemistry. The SLC4A4 knockdown cell model was structured by lentiviral infection, and the knockdown efficiency was validated by RT-qPCR and Western blotting. The effects of SLC4A4 knockdown on cell proliferation, apoptosis and cycle, migration, and invasion were detected by Celigo cell counting assay and CCK-8 assay, flow cytometry analysis, wound-healing, and Transwell assay, respectively. Tumor growth in nude mice was surveyed by in vivo imaging and Ki-67 staining. Furthermore, underlying mechanism of SLC4A4 silence induced inhibition of PCa progression was explored by human phospho-kinase array. RESULTS: Our results revealed that SLC4A4 expression was up-regulated in PCa tissues and human PCa cell lines. High expression of SLC4A4 in tumor specimens was significantly correlated with disease progression. SLC4A4 knockdown inhibited cell proliferation, migration and invasion, while facilitated apoptosis, which was also confirmed in vivo. Moreover, SLC4A4 promoted PCa progression through the AKT-mediated signalling pathway. CONCLUSION: The results of this study indicated that SLC4A4 overexpression was closely associated with the progression of PCa; SLC4A4 knockdown suppressed PCa development in vitro and in vivo. SLC4A4 acts as a tumor promotor in PCa by regulating key components of the AKT pathway and may therefore act as a potential therapeutic target for PCa treatment.

Clinical characteristics, treatment patterns and relapse in patients with clinical stage IS testicular cancer.

PURPOSE: Clinical stage I (CSI) testicular germ cell tumors (TGCT) represents disease confined to the testis without metastasis and CSIS is defined as persistently elevated tumor markers (TM) after orchiectomy, indicating subclinical metastatic disease. This study aims at assessing clinical characteristics and oncological outcome in CSIS. METHODS: Data from five tertiary referring centers in Germany were screened. We defined correct classification of CSIS according to EAU guidelines. TM levels, treatment and relapse-free survival were assessed and differences between predefined groups (chemotherapy, correct/incorrect CSIS) were analyzed with Fisher's exact and Chi-square test. RESULTS: Out of 2616 TGCT patients, 43 (1.6%) were CSIS. Thereof, 27 were correctly classified (cCSIS, 1.03%) and 16 incorrectly classified (iCSIS). TMs that defined cCSIS were in 12 (44.4%), 10 (37%), 3 (11.1%) and 2 (7.4%) patients AFP, ß-HCG, AFP plus ß-HCG and LDH, respectively. In the cCSIS group, six patients were seminoma and 21 non-seminoma. Treatment consisted of active surveillance, carboplatin-mono AUC7 and BEP (bleomycin, etoposide and cisplatin). No difference between cCSIS and iCSIS with respect to applied chemotherapy was found (p = 0.830). 5-year relapse-free survival was 88.9% and three patients (11%) in the cCSIS group relapsed. All underwent salvage treatment (3xBEP) with no documented death. CONCLUSION: Around 1% of all TGCT were classified as cCSIS patients. Identification of cCSIS is of critical importance to avoid disease progression and relapses by adequate treatment. We report a high heterogeneity of treatment patterns, associated with excellent long-term survival irrespective of the initial treatment approach.

Testicular germ cell tumours' clinical stage I: comparison of surveillance with adjuvant treatment strategies regarding recurrence rates and overall survival-a systematic review.

PURPOSE: Testicular germ cell tumours (GCTs) represent the most common malignancy in young adult males with two thirds of all cases presenting with clinical stage I (CSI). Active surveillance is the management modality mostly favoured by current guidelines. This systematic review assesses the treatment results in CSI patients concerning recurrence rate and overall survival in non-seminoma (NS) and pure seminoma (SE) resulting from surveillance in comparison to adjuvant strategies. METHODS/SYSTEMATIC REVIEW: We performed a systematic literature review confining the search to most recent studies published 2010-2021 that reported direct comparisons of surveillance to adjuvant management. We searched Medline and the Cochrane Library with additional hand-searching of reference lists to identify relevant studies. Data extraction and quality assessment of included studies were performed with stratification for histology (NS vs. SE) and treatment modalities. The results were tabulated and evaluated with descriptive statistical methods. RESULTS: Thirty-four studies met the inclusion criteria. In NS patients relapse rates were 12 to 37%, 0 to 10%, and 0 to 11.8% for surveillance, chemotherapy and for retroperitoneal lymph node dissection (RPLND) while overall survival rates were 90.7-100%, 91.7-100%, and 97-99.1%, respectively. In SE CSI, relapse rates were 0-22.3%, 0-5%, and 0-12.5% for surveillance, radiotherapy, chemotherapy, while overall survival rates were 84.1-98.7%, 83.5-100%, and 92.3-100%, respectively. CONCLUSION: In both histologic subgroups, active surveillance offers almost identical overall survival as adjuvant management strategies, however, at the expense of higher relapse rates. Each of the management strategies in CSI GCT patients have specific merits and shared-decision-making is advised to tailor treatment.

Determinants of clinical outcomes of gastric cancer patients treated with neoadjuvant chemotherapy: a sub-analysis of the PRODIGY study.

BACKGROUND: In this post hoc analysis of the PRODIGY study, we aimed to investigate factors associated with survival outcomes and provide evidence for designing optimal perioperative treatment strategies for gastric cancer patients receiving neoadjuvant chemotherapy. PATIENTS AND METHODS: A total of 212 patients in the neoadjuvant chemotherapy group of the PRODIGY study were included as the study population. The prognostic impact of clinicopathologic factors, including the initial radiological clinical stage (cStage) and post-neoadjuvant chemotherapy pathological stage (ypStage), was analyzed. RESULTS: The median age was 58 years. The majority of patients (77.4%) had cStage III disease, and about 10% and 25% had ypStage 0 and I disease, respectively. According to the initial cStage, progression-free survival (PFS) and overall survival (OS) were significantly different (P < 0.01). PFS and OS were also different according to the ypStage (P < 0.01). In multivariate analyses, cStage IIIC disease (vs. cStage II) and ypStage II and III disease (vs. ypStage 0/I) were independent factors for poor survival outcomes. Based on the patterns of PFS and OS according to both cStage and ypStage, three patient groups were defined. These groups showed distinct PFS and OS (P < 0.01) with 5-year PFS rates of 95.7%, 77.9%, and 31.3% and 5-year OS rates of 95.7%, 82.4%, and 42.5%, respectively. CONCLUSIONS: Both initial cStage and ypStage were independent factors for survival outcomes of gastric cancer patients treated with neoadjuvant chemotherapy. Efforts should be made to develop optimal peri-operative treatment strategies for patients at different risks according to cStage and ypStage.

Proper surgical extent for clinical Stage I right colon cancer.

PURPOSE: Pre-operative evaluation identifying clinical-stage affects the decision regarding the extent of surgical resection in right colon cancer. This study was designed to predict a proper surgical resection through the prognosis of clinical Stage I right colon cancer. PATIENTS AND METHODS: We included patients who were diagnosed with clinical and pathological Stage I right-sided colon cancer, including appendiceal, caecal, ascending, hepatic flexure and proximal transverse colon cancer, between August 2010 and December 2016 in two tertiary teaching hospitals. Patients who underwent open surgeries were excluded because laparoscopic surgery is the initial approach for colorectal cancer in our institutions. RESULTS: Eighty patients with clinical Stage I and 104 patients with pathological Stage I were included in the study. The biopsy reports showed that the tumour size was larger in the clinical Stage I group than in the pathological Stage I group (3.4 vs. 2.3 cm, P < 0.001). Further, the clinical Stage I group had some pathological Stage III cases (positive lymph nodes, P = 0.023). The clinical Stage I group had a higher rate of distant metastases (P = 0.046) and a lower rate of overall (P = 0.031) and cancer-specific survival (P = 0.021) than the pathological Stage I group. Compared to pathological Stage II included in the period, some of the survival curves were located below the pathological Stage II, but there was no statistical difference. CONCLUSION: The study results show that even clinical Stage I cases, radical resection should be considered in accordance with T3 and T4 tumours.

Twenty-year trends in prostate cancer stage and grade migration in a large contemporary german radical prostatectomy cohort.

BACKGROUND: A trend towards inverse stage migration in prostate cancer (PCa) was reported. However, previous analyses did not take into account potential differences in sampling strategies (number of biopsy cores), which might have confounded these reports. MATERIAL AND METHODS: Within our single-institutional database we identified PCa patients treated with radical prostatectomy (RP) between 2000 and 2020 (n = 21,646). We calculated the estimated annual percentage change (EAPC) for D'Amico risk groups, biopsy Gleason Grade Group (GGG), PSA and cT stage as well as postoperative RP GGG and pT stage relying on log linear regression methodology. Subsequently, we repeated the analyses after adjustment for number of cores obtained at biopsy. RESULTS: Absolute rates of D'Amico low risk decreased (-30.1%), while intermediate and high risk increased (+21.2% and +9.0%, respectively). Rates of GGG I decreased (-50.0%), while GGG II-V increased, with the largest increase in GGG II (+22.5%). This trend, albeit less pronounced, was also recorded after adjusted EAPC analyses (p < .05). Specifically, EAPC values for D'Amico low vs intermediate vs high risk were -1.07%, +0.37%, +0.45%, respectively, and EAPC values for GGG ranged between -0.71% (GGG I) and +0.80% (GGG IV). Finally, an increase in ≥cT2 (EAPC: +3.16%) was displayed (all p < .001). These trends were confirmed in EAPC calculations in RP GGG and pT stages (p < .001). CONCLUSION: Our findings confirm the trend towards less frequent treatment of low risk PCa and more frequent treatment of high risk PCa, also after adjustment for number of biopsy cores.

Is axillary imaging for invasive lobular carcinoma accurate in determining clinical node staging?

PURPOSE: Preoperative evaluation of clinical N-stage (cN) is difficult in breast cancer patients with invasive lobular carcinoma (ILC). Our goal was to assess the predictive value of axillary imaging in ILC by comparing imaging cN and pathologic N-stage (pN). METHODS: A single-institution retrospective review was performed for newly diagnosed stage I-III ILC patients undergoing preoperative breast imaging from 2011 to 2016. Clinicopathologic factors; mammogram, MRI, and ultrasound findings; and surgical pathology data were reviewed. Sub-analysis for pN2-N3 patients was performed to determine imaging sensitivity for patients with a larger nodal disease burden. Statistical analysis included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each imaging modality. RESULTS: Of the total 349 patients included, 70.5% were cN0, and 62% were pN0 (p = 0.03). For all patients, mammogram sensitivity was 7%, specificity 97%, PPV 50%, NPV 72%; ultrasound sensitivity was 26%, specificity 86%, PPV 52%, NPV 67%; MRI sensitivity was 7%, specificity 98%, PPV 80%, NPV 51%. For pN2/N3 patients, 38% were identified as cN0. Mammogram sensitivity was 10%; ultrasound 42%; MRI 65%. Pathology evaluation of N2/N3 patients indicated LN were replaced with ILC but maintained normal architecture. The average largest pathologic tumor deposit (1.5 ± 0.8 cm) correlated with average largest imaging LN size (1.4 ± 0.6 cm) (p = 0.58). CONCLUSION: A statistically significant difference between clinical and pathologic N-stage exists for ILC patients. MRI was most sensitive for identification of pN2-N3 patients and should be considered part of routine axillary imaging evaluation for ILC patients.

Long-Term Outcomes of Laparoscopic Radical Gastrectomy for Highly Advanced Gastric Cancer: Final Report of a Prospective Phase II Trial (KUGC04).

BACKGROUND: This is the final report evaluating the long-term outcomes of a single-arm phase II clinical trial that demonstrated the short-term efficacy of laparoscopic gastrectomy (LG) for highly advanced gastric cancer (AGC) [KUGC04]. PATIENTS AND METHODS: Seventy-three patients with histologically confirmed gastric adenocarcinoma and diagnosed with clinical stage II or higher, who potentially underwent curative resection between August 2009 and November 2014, were prospectively enrolled. Long-term outcomes with 5-year progression-free survival (PFS) and 5-year overall survival (OS) were evaluated according to clinical or pathological stages. Recurrence and progression patterns were also investigated. These outcomes were compared with those of previous reports to assess the applicability of LG for highly advanced gastric cancer (HAGC). RESULTS: The median observation period of all surviving patients was 75.1 months. The 5-year PFS and 5-year OS of all patients was 47.4% and 54.4%, respectively. Clinical stage-specific 5-year PFS and 5-year OS was 75.0, 69.1, 53.9, 39.4, 40.0 and 9.1, and 75.0, 68.8, 61.5, 45.0, 60.0 and 27.3, respectively, in stages IIA, IIB, IIIA, IIIB, IIIC, and IV, respectively. Pathological stage-specific 5-year PFS and 5-year OS, including ypStage with preoperative chemotherapy, was 100, 80.0, 100, 62.5, 80.0, 51.3, 16.7, 22.2 and 12.5, and 100, 80.0, 100, 75.0, 80.0, 64.2, 25.0, 33.3 and 12.5, respectively, in stage X (no residual tumor with preoperative chemotherapy), IA, IB, IIA, IIB, IIIA, IIIB, IIIC, and IV, respectively. Recurrence or progression was observed in 30 patients (41.1%). CONCLUSION: LG for HAGC performed by experienced surgeons is safe and oncologically acceptable.