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.

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.

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.

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.

Prognostic factors of patients with left-sided obstructive colorectal cancer: post hoc analysis of a retrospective multicenter study by the Japan Colonic Stent Safe Procedure Research Group.

BACKGROUND: There are many reports on the choice of treatment for and prognosis of left-sided obstructive colorectal cancer; however, few studies have focused on the prognostic factors of left-sided obstructive colorectal cancer. Therefore, we analyzed the prognostic factors using a post hoc analysis of a retrospective multicenter study in Japan. METHODS: A total of 301 patients were enrolled in this study to investigate the prognostic factors for relapse-free survival. The relationships between sex, age, decompression for bridge to surgery, depth of invasion, lymph node metastasis, postoperative complications, adjuvant chemotherapy, carcinoembryonic antigen, carbohydrate antigen 19-9, neutrophil-to-lymphocyte ratio, and relapse-free survival were examined. RESULTS: No change in the decompression method, T3 cancer, negative postoperative complications (grades 0-1 of Clavien-Dindo classification), and adjuvant chemotherapy during Stage III indicated a significantly better prognosis in a Cox univariate analysis. Lymph node metastasis was not selected as a prognostic factor. Excluding patients with <12 harvested lymph nodes (possible stage migration), lymph node metastasis was determined as a prognostic factor. In a Cox multivariate analysis, change in the decompression method, depth of invasion, lymph node metastasis (excluding N0 cases with <12 harvested lymph nodes), and adjuvant chemotherapy were prognostic factors. CONCLUSIONS: Similar to those in nonobstructive colorectal cancer, depth of invasion and lymph node metastasis were prognostic factors in left-sided obstructive colorectal cancer, and patients with <12 dissected lymph nodes experienced stage migration. Stage migration may result in disadvantages, such as not being able to receive adjuvant chemotherapy.

Exceeding 30 ELNs is strongly recommended for pT3-4N0 patients with gastric cancer: A multicenter study of survival, recurrence, and prediction model.

The argument concerning the exact minimum number of examined lymph nodes (ELNs) has continued for a long time among various regions, and no consensus has been reached for stratified pathological T stages for data to date. Data from 4607 pN0 patients with gastric cancer were analyzed. Kaplan-Meier analysis showed the similar overall survival (OS) outcomes among the 3 groups (ELNs ≤ 15, 16 ≤ ELNs ≤ 29 and ELNs ≥ 30, P = .171). However, the ELNs ≥ 30 group had a better disease-free survival (DFS) outcome compared with the others (all P < .05). An increased ELN group (ELNs ≥ 30) showed an improved OS only for pT3 patients (hazard ratio [HR] = 0.397, 95% confidence interval (CI): 0.182-0.866, P = .020), while an improved DFS for pT3 patients (HR = 0.362, 95%CI: 0.152-0.860, P = .021) and pT4 patients (HR = 0.484, 95%CI: 0.277-0.844, P = .011) in the multivariate analysis. A well discriminated and calibrated nomogram was constructed to predict the probability of the OS and DFS, with the C-index for OS and DFS prediction of 0.782 (95%CI: 0.735 to 0.829) and 0.738 (95%CI: 0.685 to 0.791), respectively. This study provides new and useful insights into the impact of ELN count on reducing stage migration and postoperative recurrence of pN0 patients with gastric cancer in 2000-2017. In conclusion, a larger number of ELNs is suggested for surgeons to prolong the prognosis of pN0 gastric cancer, especially for pT3 patients.

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.

FDG-PET/CT in high-risk primary breast cancer-a prospective study of stage migration and clinical impact.

PURPOSE: To investigate the clinical impact of FDG-PET/CT for staging and treatment planning in high-risk primary breast cancer. METHODS: Women with high-risk primary breast cancer were enrolled between September 2017 and August 2019 at Odense University Hospital, Denmark. Conventional mammography with/without MRI was performed before staging by FDG-PET/CT. We studied the accuracy of FDG-PET/CT for the detection of distant metastases, the effect on the change of treatment, and the prevalence of incidental findings. Biopsy and follow-up were used as a reference standard for the accuracy analysis. RESULTS: Of 103 women, 24 (23%) were diagnosed with distant metastases by FDG-PET/CT. Among these, breast surgery was omitted in 18 and could have been spared in six. Another sixteen (16%) patients were upstaged to more advanced loco-regional disease, leading to more extensive radiotherapy. Sensitivity and specificity for diagnosing distant metastases were 1.00 (95% confidence interval: 0.86-1.00) and 0.95 (0.88-0.99), respectively. Twenty-nine incidental findings were detected in 24 women (23%), leading to further examinations in 22 and diagnosis of eight (8/22, 36%) synchronous diseases: cancer (n = 4), thyroiditis (n = 2), aorta aneurysm (n = 1), and meningioma (n = 1). CONCLUSIONS: FDG-PET/CT had a substantial impact on staging and change of treatment in women with high-risk primary breast cancer, and further examination of incidental findings was considered clinically relevant. Our findings suggest that FDG-PET/CT should be considered for primary staging in high-risk primary breast cancer to improve treatment planning.

Pathologic upstaging in resected pancreatic adenocarcinoma: Risk factors and impact on survival.

BACKGROUND: Clinical and pathologic staging determine treatment of pancreatic cancer. Clinical stage has been shown to underestimate final pathologic stage in pancreatic cancer, resulting in upstaging. METHODS: National Cancer Database was used to identify clinical stage I pancreatic adenocarcinoma. Univariate, multivariable logistic regression, and Cox proportional hazard ratio were used to determine differences between upstaged and stage concordant patients. RESULTS: Upstaging was seen in 80.2% of patients. Factors found to be significantly associated with upstaging included pancreatic head tumors (OR 2.56), high-grade histology (OR 1.74), elevated Ca 19-9 (OR 2.09), and clinical stage T2 (OR 1.99). Upstaging was associated with a 45% increased risk of mortality compared to stage concordant disease (HR 1.44, p < .001). CONCLUSION: A majority of clinical stage I pancreatic cancer is upstaged after resection. Factors including tumor location, grade, Ca 19-9, and tumor size can help identify those at high risk for upstaging.

The assessment of risk factors for long-term survival outcome in ypN0 patients with rectal cancer after neoadjuvant therapy and radical anterior resection.

BACKGROUND: The main negative prognostic factors in patients with rectal cancer after radical treatment include regional lymph node involvement, lymphovascular invasion, and perineural invasion. However, some patients still develop cancer recurrence despite the absence of the above risk factors. The aim of the study was to assess clinicopathological factors influencing long-term oncologic outcomes in ypN0M0 rectal cancer patients after neoadjuvant therapy and radical anterior resection. METHODS: A retrospective survival analysis was performed on a group of 195 patients. We assessed clinicopathological factors which included tumor regression grade, number of lymph nodes in the specimen, Charlson comorbidity index (CCI), and colorectal anastomotic leakage (AL). RESULTS: In the univariate analysis, AL and CCI > 3 had a significant negative impact on disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS). After the division of ALs into early and late ALs, it was found that only patients with late ALs had a significantly worse survival. The multivariate Cox regression analysis showed that CCI > 3 was a significant adverse risk factor for DFS (HR 5.78, 95% CI 2.15-15.51, p < 0.001), DSS (HR 7.25, 95% CI 2.25-23.39, p < 0.001), and OS (HR 3.9, 95% CI 1.72-8.85, p = 0.001). Similarly, late ALs had a significant negative impact on the risk of DFS (HR 5.05, 95% CI 1.97-12.93, p < 0.001), DSS (HR 10.84, 95% CI 3.44-34.18, p < 0.001), and OS (HR 4.3, 95% CI 1.94-9.53, p < 0.001). CONCLUSIONS: Late AL and CCI > 3 are the factors that may have an impact on long-term oncologic outcomes. The impact of lymph node yield on understaging was not demonstrated.

Clinical staging in pancreatic adenocarcinoma underestimates extent of disease.

BACKGROUND/OBJECTIVES: We sought to identify the reliability of AJCC clinical staging was in comparison to pathologic staging in surgically resected patients with pancreatic cancer. METHODS: We used the National Cancer Database Pancreas from 2004 to 2016 and evaluated patients who underwent resection for PDAC with all documented components of clinical and pathologic stage. We first evaluated the distribution of overall clinical stage and pathologic stage and then evaluated for stage migration by assessing the number of patients who shifted from a clinical stage group to a respective pathologic stage group. To further characterize the migratory pattern, we assessed the distribution of clinical and pathologic T-stage and N-stage. RESULTS: In our cohort of 28,338 patients who underwent resection for PDAC, AJCC clinical staging did not reliably predict pathologic stage. Stage migration after resection was responsible for discrepancies between the distribution of overall clinical stage and pathologic stage. The predominant migration was from patients with clinical stage I disease to pathologic stage II disease. Most patients with clinical T1 and T2 disease were upstaged to pathologic T3 disease and over half of patients with clinical N0 disease were upstaged to pathologic N1 disease after resection. DISCUSSION: Clinical staging appears to overrepresent early T1, T2, and N0 disease, and underrepresent T3 and N1 disease.

Clinical and imaging findings in cervical cancer and their impact on FIGO and TNM staging - An analysis from the EMBRACE study.

OBJECTIVE: To investigate differences in local tumour staging between clinical examination and MRI and differences between FIGO 2009, FIGO 2018 and TNM in patients with primary cervical cancer undergoing definitive radio-chemotherapy. METHODS: Patients from the prospective observational multi-centre study "EMBRACE" were considered for analysis. All patients had gynaecological examination and pelvic MRI before treatment. Nodal status was assessed by MRI, CT, PET-CT or lymphadenectomy. For this analysis, patients were restaged according to the FIGO 2009, FIGO 2018 and TNM staging system. The local tumour stage was evaluated for MRI and clinical examination separately. Descriptive statistics were used to compare local tumour stages and different staging systems. RESULTS: Data was available from 1338 patients. For local tumour staging, differences between MRI and clinical examination were found in 364 patients (27.2%). Affected lymph nodes were detected in 52%. The two most frequent stages with FIGO 2009 are IIB (54%) and IIIB (16%), with FIGO 2018 IIIC1 (43%) and IIB (27%) and with TNM T2b N0 M0 (27%) and T2b N1 M0 (23%) in this cohort. CONCLUSIONS: MRI and clinical examination resulted in a different local tumour staging in approximately one quarter of patients. Comprehensive knowledge of the differential value of clinical examination and MRI is necessary to define one final local stage, especially when a decision about treatment options is to be taken. The use of FIGO 2009, FIGO 2018 and TNM staging system leads to differences in stage distributions complicating comparability of treatment results. TNM provides the most differentiated stage allocation.

A simple method for correcting for the Will Rogers phenomenon with biometrical applications.

In its basic form, the Will Rogers phenomenon takes place when an increase in the average value of each of two sets is achieved by moving an element from one set to another. This leads to the conclusion that there has been an improvement, when in fact essentially nothing has changed. Extended versions of this phenomenon can occur in epidemiological studies, rendering their results unreliable. After describing epidemiological and clinical studies that have been affected by the Will Rogers phenomenon, this paper presents a simple method to correct for it. The method involves introducing a transition matrix between the two sets and taking probability weighted expectations. Two real-world biometrical examples, based on migration economics and breast cancer epidemiology, are given and improvements against a naïve analysis are demonstrated. In the cancer epidemiology example, we take account of estimation uncertainty. We also discuss briefly some limitations associated with our method.

The increase of stage, grading, and metastases in patients undergoing radical prostatectomy during the last decade.

PURPOSE: To investigate changes in clinical data and pathological features of prostatectomy specimens of prostate cancer (PCa) patients in a large tertiary care center over the last 12 years as potential consequence of reduced acceptance of prostate-specific antigen (PSA)-based screening and implementation of active surveillance as a therapeutic option in PCa. METHODS: We retrospectively identified all patients with PCa who underwent radical prostatectomy at our institution between 2004 and 2016 from our clinical database. We reviewed clinical and pathological data including patient age, PSA level, number of positive cores and Gleason score in prostate biopsy, and pathologic N- and T-stage, and Gleason score in radical prostatectomy specimen. RESULTS: Data of 5497 consecutive patients were analyzed. Median PSA increased from 7 (IQR 4.8-10.5) to 9 ng/ml (IQR 5.8-16.1; p < 0.001), and median number of positive biopsy cores increased from 3 (IQR 2-5) to 5 (IQR 3-7; p < 0.001). The proportion of patients with Gleason score ≥ 7 in biopsy and prostatectomy specimens increased from 40 to 78% and 49 to 89% (p < 0.001), respectively. The rate of locally advanced (≥ pT3a) and lymph node-positive tumors increased from 28 to 43% and 5 to 16% (p < 0.001), respectively. CONCLUSIONS: We observed a significant change in clinical and pathological findings in our prostatectomy series with a significantly higher proportion of aggressive and locally advanced PCa in recent years. These findings may be related to a reduced acceptance of PSA-based screening and the use of active surveillance as management strategy and have significant impact on daily patient care.

Migration in last decade to high-risk prostate cancer after radical prostatectomy.

OBJECTIVE: There is controversy around prostate cancer (PCa) screening through the use of PSA, due to the risk of overtreatment. The current trend observed in various European and American studies is a decrease in the number of radical prostatectomy (RP) in low-risk PCa and an increase for intermediate or locally advanced diseases. The objective of this study was to observe the migration of the pathological stages from radical prostatectomy (RP) over 10 years in France through 2 French centers. METHODS: It was a multicentric retrospective study, where all the RP realized in 2 French tertiary centers, in a laparoscopic or retropubic approach for each of the years 2005, 2010 and 2015 were included. Preoperative data (age, PSA, clinical stage, number of positive biopsies, Gleason biopsy score) and postoperative data (pTNM, pathological Gleason score (pGS)) were analyzed and compared. RESULTS: In all, 1282 RP were realized (503 in 2005, 403 in 2010, 376 in 2015). Respectively between 2005, 2010, 2015 the average number of positive biopsy increased significantly from 2.30 vs. 2.88 vs. 5.3 (P=0.0001). The distribution of D'Amico's risk evolves with time: low-risk: 49.9 vs. 44.4 vs. 15.7% (P=0.0001); intermediate risk: 40.95 vs. 43.92 vs. 64.1% (P=0.0001) and high-risk: 9.15 vs. 11.66 vs. 20.2% (P=0.0001) between 2005, 2010 and 2015 respectively. pGS evolved to higher score with SG<7: 22.8 vs. 29.9 vs. 7.1% et SG≥7: 77.2 vs. 70.1 vs. 92.9% (P=0.001). Also, pTNM increased to non-organ-confined disease: pT2: 66.9 vs. 51.9 vs. 48.7%; pT3: 33.1 vs. 48.1 vs. 51.3% (P=0.0001). CONCLUSION: This study showed a change in the management of PCa since new recommendations from medical authorities about PSA screening and evolving of conservative treatment. Number of RP increase for higher risk PCa. This change corresponds to better patient selection for RP: decrease for low-risk and increase for high-risk organ-confined disease. LEVEL OF EVIDENCE: 3.

Treatment choice for early-stage hepatocellular carcinoma in real-world practice: impact of treatment stage migration to transarterial chemoembolization and treatment response on survival.

OBJECTIVE: The objectives of our study were firstly to characterize the treatment stage migration phenomenon in early (Barcelona Clinic Liver Cancer [BCLC]-0/A) stage hepatocellular carcinoma (HCC) by comparing the efficacy of curative therapies with trans-arterial chemoembolization [TACE] and secondly, determining baseline and on-treatment predictors of survival. METHODS: All patients within BCLC-0/A stage from six tertiary hospitals who received curative therapy with either resection, transplantation, or ablation or TACE as first-line treatment were included in the analyses. The primary endpoint was overall survival; secondary end-points were transplant-free survival and recurrence-free survival. RESULTS: Between January 2000 and December 2013, we identified 253 BCLC-0/A HCC patients of whom 148 (58.5%) received curative therapy and 105 (41.5%) migrated to TACE. Patients undergoing TACE had lower median survival (2.7 vs. 6.7 years; p < .0001), transplant-free survival (2.6 vs. 4.8 years; p < .0001) and recurrence-free survival (1.3 vs. 2.7 years; p < .001). On multivariate analysis treatment allocation to TACE was an independent prognostic predictor for both lower overall survival (HR 1.70, p = .04) and for HCC recurrence (HR 2.25, p < .001). The main prognostic determinant for each target outcome was Child-Pugh score. CONCLUSIONS: Our study confirms that curative treatments should always be preferred when applicable in early-stage HCC, but that in cases where this is not possible, TACE is a reasonable albeit inferior treatment option. In addition, it provides unique prognostic information on a significant proportion of patients with early-stage disease in whom curative therapy is not applicable.

Why is colon cancer survival improving by time? A nationwide survival analysis spanning 35 years.

There is limited information present to explain temporal improvements in colon cancer survival. This nationwide study investigates the temporal changes in survival over a 35-year period (1970-2004) in Iceland and uses incidence, mortality, surgery rate, stage distribution, lymph node yield, tumor location and histological type to find explanations for these changes. Patients diagnosed with colon cancer in Iceland 1970-2004 were identified (n = 1962). All histopathology was reassessed. Proportions, age-standardized incidence and mortality, relative, cancer-specific and overall survival and conditional survival were calculated. When comparing first and last diagnostic periods (1970-1978 and 1997-2004), 5-year relative survival improved by 12% for men and 9% for women. At the same time surgery rate increased by 12% and the proportion of stage I increased by 9%. Stage-stratified, improved 5-year relative survival was mainly observed in stages II and III and coincided with higher lymph node yields, proportional reduction of stage II cancers and proportional increase of stage III cancers, indicating stage migration between these stages. Improvement in 1-year survival was mainly observed in stages III and IV. Five-year survival improvement for patients living beyond 1 year was minimum to none. There were no changes in histology that coincided with neither increased incidence nor possibly influencing improved survival. Concluding, as a novel finding, 1-year mortality, which previously has been identified as an important variable in explaining international survival differences, is in this study identified as also being important in explaining temporal improvements in colon cancer survival in Iceland.

Impact of stage migration and practice changes on high-risk prostate cancer: results from patients treated with radical prostatectomy over the last two decades.

OBJECTIVE: To evaluate the impact of year of surgery on clinical, pathological and oncological outcomes of patients with high-risk prostate cancer. PATIENTS AND METHODS: We evaluated 1 033 patients with clinically high-risk prostate cancer, defined as the presence of at least one of the following risk factors: preoperative prostate-specific antigen (PSA) level >20 ng/mL, and/or clinical stage ≥T3, and/or biopsy Gleason score ≥8. Patients were treated between 1990 and 2013 at a single institution. The year-by-year trends in clinical and pathological characteristics were examined. Multivariable Cox regression analysis was used to test the relationship between year of surgery and oncological outcomes. RESULTS: We observed a decrease over time in the proportion of patients with high-risk disease (preoperative PSA >20 ng/mL or clinical stage cT3). A trend in the opposite direction was seen for biopsy Gleason score ≥8 tumours. We observed a considerable increase in the median number of lymph nodes removed, which was associated with an increased rate of lymph node invasion (LNI). On multivariable Cox regression analysis, year of surgery was associated with a reduced risk of biochemical recurrence (hazard ratio [HR] per 5-year interval 0.90, 95% confidence interval [CI] 0.84-0.96; P = 0.01) and distant metastasis (HR per 5-year interval 0.91, 95% CI 0.83-0.99; P = 0.039), after adjusting for age, preoperative PSA, pathological stage, LNI, surgical margin status, and pathological Gleason score. CONCLUSIONS: In this single-centre study, an increased diagnosis of localized and less extensive high-grade prostate cancer was observed over the last two decades. Patients with high-risk disease who were selected for radical prostatectomy showed better cancer control over time. Better definitions of what constitutes high-risk prostate cancer among contemporary patients are needed.

Prognostic impact of the number of retrieved lymph nodes in patients with gastric cancer.

BACKGROUND: In gastric cancer, although at least 16 lymph nodes of retrieved lymph nodes (RLNs) are recommended for nodal staging in Japanese Classification of Gastric Carcinoma and TNM classifications, we wished to clarify their appropriateness. STUDY DESIGN: A total of 1289 consecutive gastric cancer patients, who underwent gastrectomy between 1997 and 2011, were analyzed retrospectively. RESULTS: (i) The patients were divided into two groups using a cut-off RLN number of 16 (RLN < 16 or RLN ≥ 16). There were significant differences in the survival rates of patients in pStage II (P < 0.0001) and III (P = 0.0009), but not those of patients in pStage I (P = 0.0627) and IV (P = 0.1553). (ii) In 498 consecutive patients in pStage II and III, compared with patients in the RLN ≥ 16 group, those in the RLN < 16 group had a significantly higher incidence of older age (P = 0.0004) and positive lymph node ratio (PLNR) (P < 0.0001). Univariate and multivariate analyses showed that an RLN number of less than 16 was an independent poor prognostic factor (P < 0.0001, HR 2.48 [95% CI: 1.60-3.70]). (iii) A cut-off RLN number of 16 could cause the stage migration effect in pStage II or III patients. A cut-off RLN number of 25 or more could eliminate the prognostic effect. CONCLUSION: The RLN number may potentially affect the prognosis and the stage migration in pStage II or III gastric cancer patients. An RLN number of 25 or more could be sufficient for nodal staging.

Lymph node hypoplasia is associated with adverse outcomes in node-negative colon cancer using advanced lymph node dissection methods.

PURPOSE: Lymph node size as a prognostic parameter has not been investigated well in the past. Recent data, however, have indicated that this parameter could be even more important than the lymph node count. METHODS: Based on the results of earlier studies, we analyzed the lymph node size and number of node-negative colon cancer patients with regard to survival. Data from 115 node-negative cases of colon cancer were analyzed. Lymph nodes with diameters ≤5 mm were defined as small, and all other lymph nodes were classified as intermediate/large in size and labeled LN5. All of the cases were categorized according to the number of LN5s. The LN5 very low (LN5vl) group included cases with less than two LN5s. All of the other cases were assigned to the LN5 low/high (LN5l/h) group. RESULTS: The overall survival analysis revealed significantly worse outcomes for the LN5vl group, with a mean survival of 34 months compared to the LN5l/h group, with a mean survival of 40 months (P = 0.022). After adjusting for the pT1/2 and pT3/4 stages, we still found a significant outcome difference (P = 0.012). Multivariate analysis identified LN5vl and T-stage as being independently correlated with the outcome. The vast majority of LN5vl cases (91 %) were located in the left colon. The location itself, however, was not prognostic (P = 0.478). CONCLUSION: LN5 count, as a marker of immune response, could be shown as being prognostic in node-negative colon cancer. Patients with low LN5 counts showed poor outcomes. These patients could perhaps profit from adjuvant chemotherapy.