A randomised controlled trial of Standard Of Care versus RadioAblaTion in Early Stage HepatoCellular Carcinoma (SOCRATES HCC).

BACKGROUND: Therapeutic options for early-stage hepatocellular carcinoma (HCC) in individual patients can be limited by tumor and location, liver dysfunction and comorbidities. Many patients with early-stage HCC do not receive curative-intent therapies. Stereotactic ablative body radiotherapy (SABR) has emerged as an effective, non-invasive HCC treatment option, however, randomized evidence for SABR in the first line setting is lacking. METHODS: Trans-Tasman Radiation Oncology Group (TROG) 21.07 SOCRATES-HCC is a phase II, prospective, randomised trial comparing SABR to other current standard of care therapies for patients with a solitary HCC ≤ 8 cm, ineligible for surgical resection or transplantation. The study is divided into 2 cohorts. Cohort 1 will compromise 118 patients with tumors ≤ 3 cm eligible for thermal ablation randomly assigned (1:1 ratio) to thermal ablation or SABR. Cohort 2 will comprise 100 patients with tumors > 3 cm up to 8 cm in size, or tumors ≤ 3 cm ineligible for thermal ablation, randomly assigned (1:1 ratio) to SABR or best other standard of care therapy including transarterial therapies. The primary objective is to determine whether SABR results in superior freedom from local progression (FFLP) at 2 years compared to thermal ablation in cohort 1 and compared to best standard of care therapy in cohort 2. Secondary endpoints include progression free survival, overall survival, adverse events, patient reported outcomes and health economic analyses. DISCUSSION: The SOCRATES-HCC study will provide the first randomized, multicentre evaluation of the efficacy, safety and cost effectiveness of SABR versus other standard of care therapies in the first line treatment of unresectable, early-stage HCC. It is a broad, multicentre collaboration between hepatology, interventional radiology and radiation oncology groups around Australia, coordinated by TROG Cancer Research. TRIAL REGISTRATION: anzctr.org.au, ACTRN12621001444875, registered 21 October 2021.

The value of the radiological diameter-to-thickness ratio in patients with HER2-positive resectable advanced gastric cancer: implications for long survival and stage migration.

PURPOSE: To investigate the clinical significance and stage migration effect of radiological diameter-to-thickness (DT) ratio in HER2-positive resectable advanced gastric cancer (HER2-p RAGC). METHODS: 369 HER2-p RAGC patients were retrospectively enrolled and information on clinical pathological characteristics, radiological DT ratio, and outcomes [i.e., overall survival (OS) and progression-free survival (PFS)] was collected. Pearson's Chi-square and Student's t-test were employed to compare baseline characteristics. Clinical outcomes were estimated using Kaplan-Meier analysis and Log-rank test. Univariate and multivariate Cox regression models were utilized to analyze independent prognostic factors. RESULTS: HER2-p RAGC patients were stratified into two groups using a DT ratio cutoff value of 4.0 (p < 0.05). Patients with a DT ratio < 4.0 exhibited significantly longer OS (58.0 vs. 31.0 months) and PFS (43.0 vs. 24.0 months) than those with a DT ratio ≥ 4.0. DT ratio significantly predicted prognosis for N0 and II stage patients (p < 0.05). Patients with gastric body and antrum cancers demonstrated longer OS and PFS in the DT ratio < 4.0 group (p = 0.046, 0.017, 0.036 and 0.028). Multivariate Cox proportional hazard model identified age, pathological T category, pathological N category, pathological TNM category and DT ratio as independent prognostic factors. Notably, pStage II patients with a DT ratio ≥ 4.0 exhibited a similar prognosis to pStage III patients with a DT ratio < 4.0 (p = 0.418 for OS, 0.867 for PFS). CONCLUSION: Radiological DT ratio could evaluate the prognosis and detect higher malignant cases in HER2-p RAGC patients. Moreover, DT ratio might guide clinicians make postoperative strategies. TRIAL REGISTRATION: Retrospectively registered.

Stage Migration in Canine Multicentric Lymphoma: Impact of Diagnostic Techniques on Assessing Disease Extent.

BACKGROUND/AIM: Stage migration, a phenomenon triggered by technological advancements allowing more sensitive tumor spread detection, results in alterations in the distribution of cancer stages within a population. Canine multicentric lymphoma is staged I to V based on the affected anatomic site(s) and substage a or b depending on the presence of tumor-related clinical signs. The primary objective of this study was to assess the influence of various diagnostic techniques on staging accuracy and determine whether multiple staging methods lead to significant stage migration, impacting the reliability of disease stage assignments. MATERIALS AND METHODS: Dogs cytologically diagnosed with multicentric lymphoma were staged using four different staging methods (A-D): A (physical examination, hemogram, blood smear), B (A plus thoracic X-ray, abdominal ultrasound), C (B plus liver and spleen cytology) and D (C plus bone marrow cytology). RESULTS: Twenty-three dogs were enrolled: 16 females (70%) and seven males (30%). Regarding immunophenotype, 21 dogs (91.3%) were B-cell and two dogs (8.7%) were T-cell. Stage migration was observed between all staging methods. Between A and B, 12 animals migrated from stage III to stage IV. Between B and C, four animals migrated, three to a higher stage (stage III to IV) and one to a lower stage (stage IV to III). Between C and D, one animal migrated from stage IV to V. The differences between staging methods A and B were statistically significant (p≤0.001). CONCLUSION: Stage migration in canine multicentric lymphoma depends on the diagnostic methods used and reinforces the need to use standardized staging methods to avoid it.

Challenging the Dogma: Stage migration or negative lymph nodes, which of them is the main player on gastric cancer prognosis?

Expanding loco-regional nodes harvesting is expected to increase survival. This improvement may be associated to stage migration (SM). However, the great bulk of harvested lymph nodes observed in large dissections is negative. M&M: 830 patients who received R0 gastrectomy for adenocarcinoma were included. pN+ patients with <26 nodes (n = 209) were included for a simulation to "offer 26 nodes" - SM (proportional and exponential based) was simulated and analysed through machine learning algorithms. Overall Survival (OS), in native and simulated stages, were compared. OS of extended lymphadenectomies (pN+, D ≥ 26, n = 273) was compared with the simulated curves. OS of patients in the following dissection intervals of negative nodes were compared: <16 (n = 233), 16-25 (n = 258), ≥26 (n = 339). RESULTS: After simulation to 26 nodes (pN+, D < 26 patients, n = 209), staging was recomputed. OS of native vs simulated early-stages (I-II) and advanced stages (III) were not different (p > 0.05). OS of patients with lymphadenectomy (≥26) was better than simulated for early and advanced stages (p = 0.008; p = 0.005). OS of patients included in distinct intervals of negative lymph nodes were different (p < 0.001). These intervals were an independent prognostic factor (multivariate analysis). CONCLUSIONS: The influence of Stage Migration was null in this set of simulations and Will Rogers phenomenon was not observed. Extended dissection performed better in OS. But the influence of the number of negative nodes, even in large dissections, was highlighted. By emphasizing the role of negative nodes, we aim to facilitate more informed decision-making in management of gastric cancer patients, ultimately leading to improved treatment outcomes and patient care.

The prognostic role of next-generation imaging-driven upstaging in newly diagnosed prostate cancer patients.

PURPOSE: Phase III evidence showed that next-generation imaging (NGI), such as prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT), provides higher diagnostic accuracy than bone scan and contrast-enhanced computed tomography (conventional imaging, CI) in the primary staging of intermediate-to-high-risk prostate cancer (PCa) patients. However, due to the lack of outcome data, the introduction of NGI in routine clinical practice is still debated. Analysing the oncological outcome of patients upstaged by NGI (though managed according to CI) might shed light on this issue, supporting the design of randomised trials comparing the effects of treatments delivered based on NGI vs. CI. METHODS: We prospectively enrolled a cohort of 100 biopsy-proven intermediate-to-high-risk PCa patients staged with CI and PSMA PET/CT (though managed according to the CI stage), to assess the frequency of the stage migration phenomenon. Stage migration was then assessed as biochemical recurrence-free survival (bRFS) predictor. RESULTS: Three patients were lost at follow-up after imaging. PSMA PET/CT upstaged 26.8% of patients compared to CI, while it downstaged 6.1% of patients. Notably, 50% of patients excluded from surgery due to the presence of bone metastases at CI would have been treated with radical-intent approaches if PSMA PET/CT had guided the treatment choice. After a median follow-up of 6 months of surgically treated patients, 22/83 (26.5%) had biochemical recurrence (BCR). PSMA PET/CT-driven upstaging determined a significant risk increase for BCR (HR:3.41, 95%CI:1.21-9.56, p = 0.019). Including stage migration in a univariable and multivariable model identified PSMA PET/CT-upstaging as an independent predictor of bRFS. CONCLUSIONS: In conclusion, implementing NGI for staging purposes improves the prediction of bRFS. Although phase III evidence is still needed, this advancement suggests that NGI may better identify patients who would benefit from local treatments than those who may achieve better oncological outcomes through systemic treatment.

Impact of preoperative [18F]FDG PET/CT vs. contrast-enhanced CT in the staging and survival of patients with clinical stage I and II non-small cell lung cancer: a 10-year follow-up study.

OBJECTIVES: To elucidate the impact of [18F]FDG positron emission tomography/computed tomography (PET/CT) vs. CT workup on staging and prognostic evaluation of clinical stage (c) I-II NSCLC. METHODS: We retrospectively identified 659 cI-II NSCLC who underwent CT (267 patients) or preoperative CT followed by PET/CT (392 patients), followed by curative-intended complete resection in our hospital from January 2008 to December 2013. Differences were assessed between preoperative and postoperative stage. Five-year disease-free survival (DFS) and overall survival (OS) rates were calculated using the Kaplan-Meier approach and compared with log-rank test. Impact of preoperative PET/CT on survival was assessed by Cox regression analysis. RESULTS: The study included 659 patients [mean age, 59.5 years ± 10.8 (standard deviation); 379 men]. The PET/CT group was superior over CT group in DFS [12.6 vs. 6.9 years, HR 0.67 (95% CI 0.53-0.84), p < 0.001] and OS [13.9 vs. 10.5 years, HR 0.64 (95% CI 0.50-0.81), p < 0.001]. In CT group, more patients thought to have cN0 migrated to pN1/2 disease as compared with PET/CT group [26.4% (66/250) vs. 19.2% (67/349), p < 0.001], resulting in more stage cI cases being upstaged to pII-IV [24.7% (49/198) vs. 16.1% (47/292), p = 0.02], yet this was not found in cII NSCLC [27.5% (19/69) vs. 27.0% (27/100), p = 0.94]. Cox regression analysis identified preoperative PET/CT as an independent prognostic factor of OS and DFS (p = 0.002, HR = 0.69, 95% CI 0.54-0.88; p = 0.004, HR = 0.72, 95% CI 0.58-0.90). CONCLUSION: Addition of preoperative [18F]FDG PET/CT was associated with superior DFS and OS in resectable cI-II NSCLC, which may result from accurate staging and stage-appropriate therapy.

Adjuvant Radiation in Resectable Node-Positive Merkel Cell Carcinoma in the Immunotherapy Era: Implications for Future and Ongoing Trials.

Merkel cell carcinoma (MCC) is a cutaneous malignancy often treated with surgical resection followed by adjuvant radiation therapy (RT). In the node-positive setting, adjuvant RT reduces the risk of locoregional recurrence, but historical data suggest that distant failure is a persistent issue and often fatal. This has prompted new efforts to intensify treatment in these patients with the addition of neoadjuvant or adjuvant immune checkpoint inhibitor therapy. However, newer diagnostic techniques have led to stage migration in patients with previously subclinical metastatic disease; consequently, preventing locoregional recurrence may be a higher priority in node-positive MCC patients than was previously believed. Recent trials in node-positive MCC, such as ADMEC-O, have had lower rates of adjuvant RT utilization in treatment versus control arms, which may have attenuated the observed effect of adjuvant immunotherapy. The low utilization of adjuvant RT may have also resulted in a higher recurrence rate in patients who did not have a complete response to neoadjuvant immunotherapy in the CHECKMATE 358 trial. Altogether, these are important considerations for ongoing and future immunotherapy trials in MCC and may affect the interpretation of their results. Ongoing clinical trials may determine which patients are at low risk of recurrence when treated with immunotherapy and whether adjuvant RT could be omitted in select patients.

Speculation on optimal numbers of examined lymph node for early-stage epithelial ovarian cancer from the perspective of stage migration.

Introduction: In early-stage epithelial ovarian cancer (EOC), how to perform lymphadenectomy to avoid stage migration and achieve reliable targeted excision has not been explored in depth. This study comprehensively considered the stage migration and survival to determine appropriate numbers of examined lymph node (ELN) for early-stage EOC and high-grade serous ovarian cancer (HGSOC). Methods: From the Surveillance, Epidemiology, and End Results database, we obtained 10372 EOC cases with stage T1M0 and ELN ≥ 2, including 2849 HGSOC cases. Generalized linear models with multivariable adjustment were used to analyze associations between ELN numbers and lymph node stage migration, survival and positive lymph node (PLN). LOESS regression characterized dynamic trends of above associations followed by Chow test to determine structural breakpoints of ELN numbers. Survival curves were plotted using Kaplan-Meier method. Results: More ELNs were associated with more node-positive diseases, more PLNs and better prognosis. ELN structural breakpoints were different in subgroups of early-stage EOC, which for node stage migration or PLN were more than those for improving outcomes. The meaning of ELN structural breakpoint varied with its location and the morphology of LOESS curve. To avoid stage migration, the optimal ELN for early-stage EOC was 29 and the minimal ELN for HGSOC was 24. For better survival, appropriate ELN number were 13 and 8 respectively. More ELNs explained better prognosis only at a certain range. Discussion: Neither too many nor too few numbers of ELN were ideal for early-stage EOC and HGSOC. Excision with appropriate numbers of lymph node draining the affected ovary may be more reasonable than traditional sentinel lymph node resection and systematic lymphadenectomy.

Overcoming barriers to lung cancer screening using a systemwide approach with additional focus on the non-screened.

BACKGROUND: The lung cancer screening program at St Elizabeth Healthcare (Kentucky, USA) began in 2013. Over 33,000 low-dose computed tomography lung cancer screens have been performed. From 2015 through 2021, 2595 lung cancers were diagnosed systemwide. A Screening Program with Impactful Results from Early Detection, reviews that experience; 342 (13.2%) were diagnosed by screening and 2253 (86.8%) were non-screened. As a secondary objective, the non-screened cohort was queried to determine how many additional individuals could have been screened, identifying barriers and failures to meet eligibility. METHODS: Our QlikSense database extracted the lung cancer patients from the Cancer Patient Data and Management System, and identified and categorized them separately as screened or non-screened populations. Stage distribution was compared in screened and non-screened groups. Those meeting age criteria, with any smoking history, were further queried for screening eligibility, accessing the electronic medical record smoking history and audit trail, and determining if enough information was available to substantiate screening eligibility. The same methodology was applied to CMS 2015 and USPSTF 2021 criteria. RESULTS: The screened and non-screened patients were accounted for in a stage migration chart demonstrating clear shift to early stage among screened lung cancer patients. Additionally, analysis of non-screened individuals is presented. CONCLUSION: Of the St Elizabeth Healthcare eligible patients attributed to primary care providers, 49.6% were screened in 2021. Despite this level of success, this study highlighted a sizeable pool of additional individuals that could have been screened. We are shifting focus to the non-screened pool of patients that meet eligibility, further enhancing the impact on our community.

Recent Advances in Perioperative Immunotherapies in Lung Cancer.

Several clinical trials have been revolutionizing the perioperative treatment of early-stage non-small cell lung cancer (NSCLC). Many of these clinical trials involve cancer immunotherapies with antibody drugs that block the inhibitory immune checkpoints programmed death 1 (PD-1) and its ligand PD-L1. While these new treatments are expected to improve the treatment outcome of NSCLC patients after pulmonary resection, several major clinical questions remain, including the appropriate timing of immunotherapy (neoadjuvant, adjuvant, or both) and the identification of patients who should be treated with neoadjuvant and/or adjuvant immunotherapies, because some early-stage NSCLC patients are cured by surgical resection alone. In addition, immunotherapy may induce immune-related adverse events that will require permanent treatment in some patients. Based on this fact as well, it is desirable to select appropriate patients for neoadjuvant/adjuvant immunotherapies. So far, data from several important trials have been published, with findings demonstrating the efficacy of adjuvant atezolizumab (IMpower010 trial), neoadjuvant nivolumab plus platinum-doublet chemotherapy (CheckMate816 trial), and several perioperative (neoadjuvant plus adjuvant) immunotherapies (AEGEAN, KEYNOTE-671, NADIM II, and Neotorch trials). In addition to these key trials, numerous clinical trials have reported a wealth of data, although most of the above clinical questions have not been completely answered yet. Because there are so many ongoing clinical trials in this field, a comprehensive understanding of the results and/or contents of these trials is necessary to explore answers to the clinical questions above as well as to plan a new clinical trial. In this review, we comprehensively summarize the recent data obtained from clinical trials addressing such questions.

The impact of the Covid-19 pandemic on the stage of endometrial cancer at diagnosis.

Background: Endometrial cancer generally presents at an early stage affording a high rate of surgical cure. Early in the Covid-19 pandemic it was suggested that treatment of tumors with favorable pathologic features might safely be delayed. Objective: We hypothesized that disruption to health care services during the pandemic would impact the stage at presentation for these patients. Here we compare the stage at presentation of Endometrial Cancer in the months immediately preceding the pandemic to the stage at presentation during the pandemic. Study design: Charts of patients presenting with Endometrial Cancer between January 1, 2018 and April 30, 2022 were reviewed. March 1, 2020 separated the "pre-pandemic" era from the "pandemic" era. Data was collected regarding patient age, body mass index (BMI), tumor stage, histology, grade, size, and depth of invasion. Results: 322 of 374 (86.09%) of surgically staged patients presented with FIGO stage I disease "pre-pandemic" compared to 263 of 329 (71.73%) of surgically staged patients in the "pandemic" cohort (p =.029). 2.08% pre-pandemic compared to 5.48% during the pandemic presented with FIGO stage IV (p =.015). Conclusion: We found a significant difference in the stage at presentation in endometrial cancer patients, a statistic which may be attributed to the disruption of healthcare services caused by the Covid-19 pandemic.

Thyroid cancer pathologic upstaging: Frequency and related factors.

INTRODUCTION: Histopathologic assessment of thyroid tumors can lead to stage migration. We assessed frequency of pathologic upstaging, and associations with patient and tumor factors. METHODS: Primary thyroid cancers treated between 2013 and 2015 were included from our institutional cancer registry. For tumor, nodal, and summary stage, upstaging was present when final pathologic stage was greater than clinical staging. Multivariate logistic regression and Chi-squared tests were performed. RESULTS: 5,351 resected thyroid tumors were identified. Upstaging rates for tumor, nodal, and summary stage were 17.5% (n = 553/3156), 18.0% (n = 488/2705), and 10.9% (n = 285/2607), respectively. Age, Asian race, days to surgery, lymphovascular invasion, and follicular histology were significantly associated. Upstaging was significantly more common after total vs partial thyroidectomy, for tumor (19.4% vs 6.2%, p < 0.001), nodal (19.3% vs 6.4%, p < 0.001), and summary stages (12.3% vs 0.7%, p < 0.001). CONCLUSIONS: Pathologic upstaging occurs in a considerable proportion of thyroid tumors, most commonly after total thyroidectomy. These findings can inform patient counseling.

Evaluating prognostic value and stage migration effects using a positive lymph node ratio in adenocarcinoma of the esophagogastric junction.

BACKGROUND: Adenocarcinoma of the esophagogastric junction (AEG) is increasing worldwide. Lymph node metastasis is an important clinical issue in AEG patients. This study investigated the usefulness of a positive lymph node ratio (PLNR) to stratify prognosis and evaluate stage migration. METHODS: We retrospectively analysed 117 consecutive AEG patients (Siewert type I or II) who received a lymphadenectomy between 2000 and 2016. RESULTS: A PLNR cut-off value of 0.1 most effectively stratified patient prognosis into two groups (P < 0.001). Also, prognosis could be clearly stratified into four groups: PLNR = 0, 0 < PLNR < 0.1, 0.1 ≤ PLNR < 0.2, and 0.2 ≤ PLNR (P < 0.001, 5-year survival rates (88.6%, 61.1%, 34.3%, 10.7%)). A PLNR ≥ 0.1 significantly correlated with tumour diameter ≥ 4 cm (P < 0.001), tumour depth (P < 0.001), greater pathological N-status (P < 0.001), greater pathological Stage (P < 0.001), and oesophageal invasion length ≥ 2 cm (P = 0.002). A PLNR ≥ 0.1 was a poor independent prognostic factor (hazard ratio 6.47, P < 0.001). The PLNR could stratify prognosis if at least 11 lymph nodes were retrieved. A 0.2 PLNR cut-off value discriminated a stage migration effect in pN3 and pStage IV (P = 0.041, P = 0.015) patients; PLNR ≥ 0.2 might potentially diagnose a worse prognosis and need meticulous follow-up post-surgery. CONCLUSION: Using PLNR, we can evaluate the prognosis and detect higher malignant cases who need meticulous treatments and follow-up in the same pStage.

At least 16 lymph nodes are recommended to examine during pancreaticoduodenectomy in ampullary adenocarcinoma.

The minimum number of lymph nodes to be examined during pancreaticoduodenectomy (PD) for patients with ampullary adenocarcinoma (AC) is still debatable due to limited clinical data. Therefore, here we explored the relationship between the number of examined lymph node (ELN) and the current N staging (American Joint Committee on Cancer staging system, AJCC, 8 edition) after PD for AC as well as determined the minimum number of examined lymph nodes (MNELN) to ensure the accurate detection of nodal involvement. Patients underwent PD for AC in the National Cancer Center cohort of China (NCC cohort of China) from 1998 to 2020 and in the Surveillance, Epidemiology, and End Results database (SEER database) from 2010 to 2018 were retrospectively reviewed, and a total of 452 eligible patients were included in this study. The MNELN was evaluated by binomial probability law and best survival separation methods. Furthermore, the cut-off value of MNELN was validated in the NCC cohort of China using Least Absolute Shrinkage and Selection Operator (LASSO) regression. Our analysis indicated that the median number of ELN was 14, and the number of ELN was positively correlated with N stage. The MNELN was 16, whereas the best survival separation of ELN was 38 in node-positive patients and 3 in node-negative patients. In the validation cohort, the number of 16 ELNs was identified as a predictive variable for lymph node metastasis with nonzero coefficients in the LASSO-logistic regression model. Together, we concluded that a greater number of ELN was associated with more accurate nodal status assessment in PD for AC patients. A minimum of 16 lymph nodes were required to during PD in AC patients.

Cervical cancer during the covid pandemic: Are patients presenting with more advanced or larger tumours?

OBJECTIVES: Concerns were raised by clinicians at the Oxford Gynaecological Cancer MDT that there was an increasing number of women presenting with large cervical tumours requiring chemo-radiotherapy, possibly due to delays associated with the COVID pandemic. This audit was undertaken to assess whether this was a real event. STUDY DESIGN: This retrospective cohort study collated the data from the central pathology service covering Oxfordshire, in the Oxford Gynaecological cancer centre. The control population consisted of patients treated during the 2 years pre-pandemic (1st Jan 2018-31 Dec 2019) and the study group the 2-year pandemic period (1st Jan 2020 until 31st December 2021). A total of 153 patients (74 control and 79 study) were diagnosed of cervical cancer during the study period. Variables included in the analysis were age, pathway of referral and diagnosis (cytology or clinical), FIGO stage, tumour histology, tumour size (using maximum diameter on MRI) and treatment. Student's t-test was used for continuous and discrete variables, respectively. The X2 test was used for the statistical analysis of proportions. RESULTS: There was no statistically significant differences was noted in the referral pathways during both periods. Statistically significant stage migration from FIGO stage II to III was detected (p < 0.05), though no statistically significant change in tumour size. However, the pattern of tumour volume on case-to-case comparison elicited more cases with larger volumes during the pandemic periods. CONCLUSIONS: Referral pathways of diagnosed cancer cervix was not affected during the pandemic in Oxfordshire. Therapeutic treatment numbers were unchanged - but some changes in tumour volume were likely the reason for the impression more such cases. Whether the stage shift noted here is representative of the wider population requires further studies.

The impact of local staging of prostate cancer determined on MRI or DRE at time of radical prostatectomy on progression-free survival: A Will Rogers phenomenon.

INTRODUCTION: We aimed to test whether the current practice of using mpMRI stage might lead to a Will Rogers phenomenon with a stage migration compared to DRE in men undergoing radical prostatectomy. MATERIAL AND METHODS: A total of 572 consecutive patients who underwent radical prostatectomy at a single institution (2007-2017) were included. Clinical stage using digital rectal examination was determined on table by the operating surgeon; mpMRI and pathological stage were recorded after tumor board review. Progression-free survival (PFS) was defined as no rising PSA, no adjuvant/salvage treatment, and no metastases or mortality. PFS was compared between groups and a model incorporating mpMRI into the EAU risk groups was created. RESULTS: Median age was 63 years (IQR 58.5-67) and median PSA was 8.9 ng/ml (IQR 6.5-13.2). Using DRE stage, 20% were NCCN low risk, 43% were intermediate, and 37% high. Median follow-up was 48 months (IQR 22-73). Estimated PFS at 1, 3, and 5 years was 75%, 59%, and 54%, respectively. When comparing PFS between DRE and mpMRI stages, patients deemed T1 (P < 0.01) or T3 (P = 0.03) by mpMRI showed better outcomes than patients staged T1 or T3 by DRE. On univariable analysis lower risk for failure was seen for MRI T1 disease (HR 0.10 95%, CI 0.01-0.73, P = 0.02) or MRI T3 (HR 0.70, CI 0.51-0.97, P = 0.03). On multivariable analysis, only MRI T1 remained a significant predictor (HR 0.08, 95% CI 0.01-0.59, P = 0.01). The subsequent, modified EAU risk model using both DRE and mpMRI performed significantly better than the DRE model. CONCLUSION: PFS based on mpMRI is not the same as DRE staging. Current risk groups which use DRE should be used with caution in whom local stage is based on mpMRI. Our modified EAU-risk categories can provide greater accuracy.

Impact of the preoperative clinical N stage on the prognosis of patients with colon cancer.

AIM: Although preoperative clinical staging (cStage) is performed for most cancer patients, limited information is currently available on the relationship with postoperative prognosis. We herein investigated the relationship between cStage and prognosis of colon cancer (CC) patients, particularly focusing on the presence or absence of clinical lymph node (LN) metastasis. METHOD: This was a retrospective study on 840 consecutive patients with colon adenocarcinoma who underwent radical resection at our institution between January 2007 and December 2018. A Kaplan-Meier curve was used to analyse the prognosis of two groups: cN(+)pN(-); a group preoperatively diagnosed with clinical LN metastasis positive, but with no pathological LN metastasis postoperatively, and cN(-)pN(-); a group without clinical and pathological LN metastasis. We also investigated whether a clinical diagnosis is a more accurate prognostic factor than other clinical factors. RESULTS: Among pN(-) cases, the 5-year recurrence-free survival rate was significantly lower in preoperatively diagnosed cN(+) cases than in cN(-) cases (79.4% vs. 95.6%, 3.04 years vs. 3.85 years, p < 0.01). In a multivariate analysis of various preoperative clinical factors in pStage II cases, including high risk factors for pStage II CC, cN(+) was identified as an independent prognostic factor (hazard ratio: 2.06, 95% CI: 1.02-4.27, p = 0.04). CONCLUSION: Preoperatively over-staged cN cases had a poorer prognosis than cases without over-staging, indicating its potential as a prognostic factor. In addition to already known high risk factors in pStage II cases, the preoperative cStage may be an indication for adjuvant chemotherapy.

Stage Migration and Lung Cancer Incidence After Initiation of Low-Dose Computed Tomography Screening.

INTRODUCTION: Despite evidence from clinical trials of favorable shifts in cancer stage and improvements in lung cancer-specific mortality, the effectiveness of lung cancer screening (LCS) in clinical practice has not been clearly revealed. METHODS: We performed a multicenter cohort study of patients diagnosed with a primary lung cancer between January 1, 2014, and September 30, 2019, at one of four U.S. health care systems. The primary outcome variables were cancer stage distribution and annual age-adjusted lung cancer incidence. The primary exposure variable was receipt of at least one low-dose computed tomography for LCS before cancer diagnosis. RESULTS: A total of 3678 individuals were diagnosed with an incident lung cancer during the study period; 404 (11%) of these patients were diagnosed after initiation of LCS. As screening volume increased, the proportion of patients diagnosed with lung cancer after LCS initiation also rose from 0% in the first quartile of 2014 to 20% in the third quartile of 2019. LCS did not result in a significant change in the overall incidence of lung cancer (average annual percentage change [AAPC]: -0.8 [95% confidence interval (CI): -4.7 to 3.2]) between 2014 and 2018. Stage-specific incidence rates increased for stage I cancer (AAPC = 8.0 [95% CI: 0.8-15.7]) and declined for stage IV disease (AAPC = -6.0 [95% CI: -11.2 to -0.5]). CONCLUSIONS: Implementation of LCS at four diverse health care systems has resulted in a favorable shift to a higher incidence of stage I cancer with an associated decline in stage IV disease. Overall lung cancer incidence did not increase, suggesting a limited impact of overdiagnosis.

Pathologic stage of ypT0N+ rectal cancers following neo-adjuvant treatment: clinical interpretation of an orphan status.

Approximately 20% of locally advanced rectal cancers treated with neoadjuvant therapy achieve a pathologic complete response, but approximately 10% of them present residual nodal metastases (ypT0N+). We aimed this research to compare the survival rates of ypT0/ypTisN+ and stage 3a rectal cancer patients. A large multicenter study recently investigated ypT0/ypTis rectal cancers treated between 2005 and 2015 in Italy and Spain. ypT0/ypTisN+ were selected and compared with stage 3a rectal cancers treated at the same institutions with upfront surgery (ySICO group). Additionally, the SEER database was searched for patients with stage 3a rectal cancers treated with surgery in the same years. Overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) were analyzed using Kaplan-Meier curves and random survival forest analysis (RSF). The ySICO study population consisted of 19 ypT0/2ypTisN+ (mean follow-up 41.8 months) and 72 Stage 3a patients (mean follow-up 56.9 months). These subgroups were comparable, but stage 3a patients were treated more frequently with adjuvant therapy (90.5% vs 61.9%, p 0.0001). No significant differences were reported between the ySICO subgroups for the OS, DFS, and DSS curves. When the 1213 SEER patients were added to Stage 3a, the RFS model failed to differentiate OS between groups that presented identical survival. Root analysis showed that adjuvant therapy was the only variable differentiating OS and DSS in the ySICO population. These findings suggest that ypT0/ypTisN+ and stage 3a rectal cancers could be ranked together based on their similar outcomes and pathologic assessment, and they stress the importance of adjuvant therapy in patients presenting with residual nodal metastases.

MDT stage migration in MRI of significant rectal polyps and early rectal cancers.

PURPOSE: To audit the diagnostic accuracy of MRI for staging early and polyp rectal cancers with the purpose of identifying scope for service improvement. METHODS: This is an IRB approved retrospective study of patients who underwent staging MRI for rectal growths followed by upfront TME type surgery or local excision without neoadjuvant therapy between 2018 and 2021. MR-T-stage was compared with surgical histopathology. The degree of stage migration in the multidisciplinary team meetings (MDT) was assessed and training needs were identified. RESULTS: 53 patients (32 males) with a mean (SD) age of 56.7 (13.6) years with 54 rectal lesions and underwent trans-anal excision (n = 18) or upfront surgery (n = 35) were included. Pathology showed < / = pT1 stage in n = 18 and > / = pT2 stage in n = 36. Radio-pathological concordance rate was 38.9% and 74.1%, respectively, for primary reports and MDT reads, respectively, and during MDT, the rates improved by 44.5% and 30.5% for < / = pT1 and > / = pT2 stages ,respectively. The overall T-stage migration rate at MDT was 44.6% (25/54) and the migration rate was higher (61.1%) for < / = pT1 stage lesions. The best sensitivity, specificity, PPV, NPV and accuracy of MRI for T-staging was 83.3%, 91.6%, 83.3%, 91.6% and 88.8%, respectively. CONCLUSION: Radio-pathological correlation for MRI T-stage is excellent for MDT reads by experienced radiologists. MDT reads lead to significant down-staging of T-stage in polyp and early rectal cancer thereby improving radio-path correlation.