De-escalating Locoregional Therapy for Axillary Micrometastases in Breast Cancer: How Much is Too Much?

BackgroundThe applicability of modern prospective data on adjuvant radiotherapy (RT) fields in patients with micrometastases is limited because many trials occurred prior to routine measurement of nodal metastasis size and modern sentinel lymph node evaluation techniques. We aimed to determine prognostic factors for patients with micrometastases and evaluate the impact of adjuvant RT on disease outcomes.Patients and MethodsPatients diagnosed with pathologic T1-T3 N1mi breast cancers between 2004-2015 were identified. Cox proportional hazards methods were used to determine characteristics predictive of locoregional recurrence (LRR). Tumor and treatment-specific factors were further evaluated using log-rank statistics to compare rates of LRR-free survival.ResultsThis analysis included 156 patients. On multivariable analysis, grade 3 histology (HR 10.84, 95% CI 2.72-43.21) and adjuvant RT (HR 0.22, 95% CI 0.06-0.81) were independent predictors of LRR. Among patients with grade 1-2 histology, 5-year LRR-free survival was 98.8% in patients who received adjuvant RT versus 100% in patients who did not receive adjuvant RT (P = .82). Among patients with grade 3 histology, 5-year LRR-free survival was 90.1% in patients who received adjuvant RT versus 53.0% in patients who did not receive adjuvant RT (P = .025), and 100% in patients receiving comprehensive nodal irradiation versus 76.7% in patients receiving whole breast irradiation or no RT (P = .045).ConclusionPatients with grade 3 micrometastases are at substantial risk for LRR. Adjuvant RT, including comprehensive nodal irradiation, should be strongly considered in these women.     

The effect of age at diagnosis on prostate cancer mortality: A grade-for-grade and stage-for-stage analysis

ObjectiveTo evaluate the effect of advancing age on cancer-specific mortality (CSM) after radical prostatectomy (RP).Materials and methodsOverall, 205,551 patients with PCa diagnosed between 1988 and 2009 within the Surveillance Epidemiology and End Results (SEER) database were included in the study. Patients were stratified according to age at diagnosis: ≤50, 51–60, 61–70, and ≥71 years. The 15-year cumulative incidence CSM rates were computed. Competing-risks regression models were performed to test the effect of age on CSM in the entire cohort, and for each grade (Gleason score 2–4, 5–7, and 8–10) and stage (pT2, pT3a, and pT3b) sub-cohorts.ResultsAdvancing age was associated with higher 15-year CSM rates (2.3 vs. 3.4 vs. 4.6 vs. 6.3% for patients aged ≤50 vs. 51–60 vs. 61–70 vs. ≥71 years, respectively; P < 0.001). In multivariable analyses, age at diagnosis was a significant predictor of CSM. This relationship was also observed in sub-analyses focusing on patients with Gleason score 5–7, and/or pT2 disease (all P ≤ 0.05). Conversely, age failed to reach the independent predictor status in men with Gleason score 2–4, 8–10, pT3a, and/or pT3b disease.ConclusionsAdvancing age increases the risk of CSM. However, when considering patients affected by more aggressive disease, age was not significantly associated with higher risk of dying from PCa. In high-risk patients, tumor characteristics rather than age should be considered when making treatment decisions.     

Impact of Adherence to Multidisciplinary Recommendations for Adjuvant Treatment in Radical Prostatectomy Patients With High Risk of Recurrence

IntroductionThe purpose of this study was to investigate adherence to recommended adjuvant radiotherapy (aRT) in radical prostatectomy (RP) patients with adverse pathologic features and to analyse the outcome of patients who followed or denied this recommendation.Patients and MethodsWe included 1140 consecutive RP patients (2006-2015) with non-organ confined (pT3) prostate cancer and either positive surgical margins (R1) and/or lymph node involvement (pN1) and non-detectable postoperative prostate-specific antigen who received multidisciplinary aRT recommendations. Patients were stratified into adherence versus non-adherence to recommendations. Additionally, subgroups within pathologic criteria (pT3R1N0, pT3R0N1, pT3R1N1) were analyzed. Kaplan-Meier, as well as multivariable Cox regression analyses were used to assess biochemical recurrence (BCR)-free survival, metastasis-free survival, cancer-specific survival, and overall survival.ResultsOverall, 508 (44.6%) patients were non-adherent. Of those, 273 (53.6%) did not receive any RT, and 235 (46.4%) received salvage RT. At 8 years, BCR-free survival was 57.7 versus 20.1%, metastasis-free survival was 76.5 versus 75.4%, cancer-specific survival was 91.7 versus 87.4%, and overall survival was 80.4 versus 75.8% in adherent versus non-adherent patients, respectively (P < .001). In multivariable Cox regression predicting BCR, metastatic progression, cancer-specific mortality, and overall mortality, non-adherence to aRT recommendation represented an independent predictor (hazard ratio [HR], 3.8; 95% confidence interval [CI], 3.1-4.5; HR, 1.6; 95% CI, 1.2-2.2; HR, 2.8; 95% CI, 1.5-5.3; and HR, 1.8; 95% CI, 1.2-2.8, respectively).ConclusionsOnly about 55% of patients followed our multidisciplinary recommendations. Adherent patients were significantly less likely to experience BCR, metastatic progression, cancer-specific mortality, and overall mortality. Thus, patients with high risk of recurrence may be advised about the possibility of improved oncologic outcomes in case of adherence to aRT recommendations.     

Association of Low Socioeconomic Status With Adverse Prostate Cancer Pathology Among African American Men Who Underwent Radical Prostatectomy

BackgroundWe tested for associations between socioeconomic status (SES) and adverse prostate cancer pathology in a population of African American (AA) men treated with radical prostatectomy (RP).Patients and MethodsWe retrospectively reviewed data from 2 institutions for AA men who underwent RP between 2010 and 2015. Household incomes were estimated using census tract data, and patients were stratified into income groups relative to the study population median. Pathologic outcomes after RP were assessed, including the postsurgical Cancer of the Prostate Risk Assessment (CAPRA-S) score and a definition of adverse pathology (stage ≥ pT3, Gleason score ≥ 4+3, or positive lymph nodes), and compared between income groups.ResultsWe analyzed data of 347 AA men. Median household income was $37,954. Low-SES men had significantly higher prostate-specific antigen values (mean 10.2 vs. 7.3; P < .01) and CAPRA-S scores (mean 3.4 vs. 2.5; P < .01), more advanced pathologic stage (T3-T4 31.8% vs. 21.5%; P = .03), and higher rates of seminal vesicle invasion (17.3% vs. 8.2%; P < .01), positive surgical margins (35.3% vs. 22.1%; P < .01), and adverse pathology (41.4% vs. 30.1%; P = .03). Linear and logistic regression showed significant inverse associations of SES with CAPRA-S score (P < .01) and adverse pathology (P = .03).ConclusionIn a population of AA men who underwent RP, we observed an independent association of low SES with advanced stage or aggressive prostate cancer. By including only patients in a single racial demographic group, we eliminated the potential confounding effect of race on the association between SES and prostate cancer risk. These findings suggest that impoverished populations might benefit from more intensive screening and early, aggressive treatment of prostatic malignancies.     

A Nationwide Persistent Underutilization of Adjuvant Radiotherapy in North American Prostate Cancer Patients

ObjectiveTo examine the utilization of adjuvant radiotherapy (aRT) in contemporary prostate cancer patients with adverse pathological features at radical prostatectomy (RP).MethodsWe identified 189,240 patients with adverse features at RP (positive margin, stage ≥pT3a, and/or pN1 disease), from 2004 to 2015, within the National Cancer Database, and validated our findings within Surveillance, Epidemiology, and End Results (SEER) program. We examined the utilization of patients with aRT with adverse features at RP and patients with very aggressive disease (at least 2 of the following: ≥pT3b, pathological Gleason 8-10, and pN1). Regression analysis examined the relationship of various predictors of utilization adjusting to confounders. Pseudo R² analysis examined the magnitude of influence that each variable had on the decision to use aRT.ResultsWithin the National Cancer Database cohort, only 11.7% of our patients received aRT. In patients with very aggressive disease, aRT utilization rate was 28.9%. Within the SEER cohort, 16.3% of patients with any adverse features at time of RP received aRT. In patients with very aggressive disease, only 30% of patients received aRT. Further, year of diagnosis, Gleason grade, pathologic stage, and positive surgical margin were the variables that had the greatest influence on the decision to use aRT, and that positive surgical margin, type of institution at which care was received, and lymph node involvement were the most influential variables in patients with very aggressive disease.ConclusionsThe current standard of care in the United States represents a significant underutilization of aRT in eligible patients with prostate cancer. Urgent efforts are necessary to address this quality-of-care concern.     

LacdiNAc-Glycosylated Prostate-specific Antigen Density is a Potential Biomarker of Prostate Cancer

BackgroundSerum LacdiNAc-glycosylated prostate-specific antigen (LDN-PSA) and LDN-PSA density together with PSA and PSA density (PSAD) were measured as a diagnostic tool for prostate cancer (PCa).Patients and MethodsWe included 150 patients with PCa without hormonal therapy and 41 patients without PCa obtained from the Kyoto University Hospital between 2012 and 2017. LDN-PSA levels were measured through a WFA–anti-PSA antibody sandwich immunoassay using a highly sensitive surface plasmon field-enhanced fluorescence spectroscopy (SPFS) system. Diagnostic performance of serum LDN-PSA and LDN-PSAD was evaluated by measuring the area under the receiver-operating characteristic curve (AUC).ResultsThe AUCs of LDN-PSA, LDN-PSAD, and PSAD levels (0.780, 0.848, and 0.835, respectively) detected in patients with PCa were significantly higher (P = .0001, P < .0001, and P < .0001, respectively) than that of PSA (0.590). Moreover, among 143 patients with PCa who received radical prostatectomy (RP), the AUCs of LDN-PSA, LDN-PSAD, and PSAD levels (0.750, 0.812, and 0.769, respectively) detected in patients with a pathologic Gleason grade group ≥ 2 were significantly higher (P = .0170, P = .0028, and P = .0003, respectively) than that of PSA (0.578). In the group comprising 35 patients who received RP with a Gleason grade group 1-graded biopsy, the LDN-PSA, LDN-PSAD, and PSAD levels were significantly different (P = .0097, P = .0024, and P = .0312, respectively). However, PSA alone could not discriminate cases with adverse features (P = .454).ConclusionsLDN-PSAD is a potential marker for detecting PCa and selecting candidates for RP.     

Radical Prostatectomy or Radiotherapy in High-Risk Prostate Cancer: A Systematic Review and Metaanalysis

BackgroundRadical prostatectomy (RP) is one of the treatment options for localized, high-risk prostate cancer (PC), but it has never been compared with external beam radiotherapy (RT), which is an alternative approach, in a large randomized trial. To compare the outcomes of patients treated with surgery versus RT, we performed a metaanalysis of available studies on this topic.Materials and MethodsWe performed a search of MEDLINE, EMBASE, Web of Science, SCOPUS, and The Cochrane Central Register of Controlled Trials (CENTRAL) for randomized or observational studies that investigated overall survival (OS) and PC-specific mortality (PCSM) risks in relation to use of surgery or RT in patients with high-risk PC. Fixed- and random-effect models were fitted to estimate the summary odds ratio (OR). Between-study heterogeneity was tested using χ² statistics and measured using the I² statistic. Publication bias was evaluated using a funnel plot and Egger regression asymmetry test.ResultsSeventeen studies were included (1 randomized and 16 retrospective). RP was associated with improved OS (OR, 0.51; 95% confidence interval [CI], 0.38-0.68; P < .00001), PCSM (OR, 0.56; 95% CI, 0.37-0.85; P = .007), and non-PCSM (OR, 0.53; 95% CI, 0.35-0.8; P = .002) compared with RT. Biochemical relapse-free survival rates were similar to those of RT.ConclusionOverall and cancer-specific mortality rates appear to be better with RP compared with RT in localized, high-risk PC. Surgery is also associated with a 50% decreased risk of non-PCSM compared with RT.     

Maximum Tumor Diameter and the Risk of Prostate-Specific Antigen Recurrence After Radical Prostatectomy

Introduction/BackgroundThe aim of this study was to investigate whether the MTD could identify men at low risk of PSA recurrence after RP who might not benefit from ART despite other adverse features.Patients and MethodsThe study cohort consisted of 354 men with T1c to T2 prostate cancer diagnosed between September 2001 and December 2008 who underwent RP without adjuvant therapy. Multivariable Cox regression was used to assess the effect of MTD on the risk of PSA recurrence (> 0.1 ng/mL and verified), adjusting for known predictors.ResultsAfter a median follow-up of 4.0 years, 34 men (9.6%) experienced PSA failure. In multivariable analysis, increasing MTD was significantly associated with an increased PSA recurrence risk (hazard ratio, 2.74; 95% confidence interval, 1.23-6.10; P = .01) within the interaction model. Estimates of PSA recurrence-free survival stratified around the median MTD value (1.2 cm) were significantly different in men with a pre-RP PSA > 4 ng/mL (P < .001; 5-year estimate: 74.5% vs. 99.0%) but not in men with PSA ≤ 4 ng/mL (P = .59; 5-year estimate: 89.6% vs. 92.6%), consistent with the significant interaction (P = .004) between PSA and MTD. Moreover, in men with a pre-RP PSA > 4 ng/mL these estimates were significantly different if at least 1 adverse feature (pT3, R1, or Gleason score ≥ 8) was present at RP (P = .01; 5-year estimate: 46.6% vs. 100%) versus none (P = .09; 5-year estimate: 93.4% vs. 98.9%).ConclusionMen with a low MTD (≤ 1.2 cm) appear to be at low risk of PSA recurrence despite adverse features at RP and might not benefit from ART.     

Outcomes for Young Men With Localized Intermediate-Risk Prostate Cancer: An Analysis of the NCDB

BackgroundPrimary management of localized, intermediate-risk prostate cancer consists of radical prostatectomy (RP), radiotherapy (RT) with short-course androgen deprivation therapy (ADT), or RT alone. The purpose of this study was to determine if these treatment strategies have equivalent overall survival (OS) in patients < 55 years old with intermediate-risk prostate cancer.Patients and MethodsWe identified 35,134 patients in the National Cancer Data Base with localized intermediate-risk prostate cancer treated with RP, RT + ADT, or RT from 2004 to 2013. Ten-year OS rates were estimated by the Kaplan-Meier method. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) were computed by multivariate Cox regression.ResultsA total of 29,920 patients (85.2%) underwent RP, 1393 (4.0%) RT + ADT, and 3821 (10.9%) RT. Median patient age was 51 years old, and median follow-up was 59.9 months. Ten-year OS was estimated to be 94.2% for RP, 80.7% for RT + ADT, and 85.2% for RT (P < .0001). On multivariate analysis, treatment with RT + ADT or RT was associated with significantly worse OS compared to treatment with RP (RT + ADT HR = 2.06, 95% CI 1.67-2.54, P < .0001; RT HR = 2.0, 95% CI 1.71-2.33, P < .0001). Patients who met all 3 of the intermediate-risk criteria showed worse OS compared to patients who met only one criterion (HR = 1.80; 95% CI, 1.32-2.44; P = .0002).ConclusionRP is significantly more likely than RT + ADT or RT to be used as a primary treatment for young men with localized intermediate prostate cancer. RP was also associated with improved OS compared to RT + ADT and RT.     

Differential prognostic impact of different Gleason patterns in grade group 4 in radical prostatectomy specimens

IntroductionThere are questions regarding whether grade group (GG) 4 prostate cancer (PC) is heterogeneous in terms of prognosis. We assessed prognostic differences in PC patients within GG 4 treated with radical prostatectomy (RP).Material and methodsBiochemical recurrence (BCR)-free, cancer-specific, and overall survival were analyzed in 787 PC patients with GG 4 based on RP pathology (Gleason score (GS) 3 + 5: 189, GS 4 + 4: 500, and GS 5 + 3: 98). Logistic regression analysis was performed to assess factors predictive of high-risk surgical pathological features. Cox regression models were used to evaluate potential prognostic factors of survival.ResultsWithin a median follow-up of 86 months, 378 patients (48.0%) experienced BCR and 96 patients (12.2%) died, 42 of whom (5.3%) died of PC. GS 5 + 3 was significantly associated with worse BCR-free and cancer-specific survival, as well as higher positive surgical margin, lymph node metastasis, extraprostatic extension, and non-organ-confined disease rates, than GS 3 + 5 and higher positive surgical margin, lymph node metastasis, extraprostatic extension, and non-organ-confined disease rates than GS 4 + 4 (P < 0.05). GS 4 + 4 was significantly associated with worse BCR-free survival and higher extraprostatic extension, and non-organ-confined disease rates than GS 3 + 5 (P < 0.05). Inclusion of the different Gleason patterns improved the discrimination of a model for prediction of all survival outcomes compared to standard prognosticators.ConclusionsThere is considerable heterogeneity within GG 4 in terms of oncological and surgical pathological outcomes. Primary and secondary Gleason patterns should be considered to stratify high-risk PC patients after RP.     

Mediastinal Up-Staging During Surgery in Non–Small-Cell Lung Cancer: Which Mediastinal Lymph Node Metastasis Patterns Better Predict The Outcome? A Multicenter Analysis

BackgroundUnexpected N2 involvement occurs in approximately 10% to 20% of patients with non–small-cell lung cancer (NSCLC) and patients’ prognostic factors remain unclear. The aim of this study was to evaluate prognostic factors in these patients.MethodsFrom January 2002 to December 2012, we retrospectively analyzed data of 550 patients with NSCLC with preoperative negative, but pathologic positive N2 involvement, who underwent anatomical lung resection and hilo-mediastinal lymphadenectomy, obtained from 6 institutions. An established prognostic factor panel and N2-type involvement were correlated to overall (OS), cancer-specific (CSS), and disease-free survival (DFS) using multivariate Cox Regression model. The following lymph node patterns were analyzed: number of resected nodes (#RNs), metastatic nodes (#MNs), ratio between #MNs and #RNs (NR), N2 subgroups proposed for the eighth TNM edition, and lobe-specific versus nonspecific metastasis.ResultsRegarding our cohort, 419 patients were staged IIIA (T1-2N2), 131 IIIB (T3-4 N2), 113 pT1, 306 pT2, 94 pT3, and 37 pT4; 5-year OS, DFS, and CSS were 34.1%, 20.1%, and 64.6%, respectively. Independent prognostic factor for OS, in the multivariable analysis, were as follows: NR <17% (P = .009), proposed N2 classification subgroups (P = .014), age <66 (P < .001), and pT (P = .005); for DFS: NR <17% (P = .003), adjuvant treatment (P = .026), and pT (P = .026); and for CSS: NR <17% (P = .008), grading (P = .001), and adjuvant treatment (P < .001).ConclusionOur study confirms that adjuvant therapy is fundamental and NR, in patients with unexpected N2 involvement, has a strong prognostic factor. In particular, a NR cutoff value of 17% could predict OS, DFS, and CSS in patients with NSCLC.     

Neoadjuvant Gemcitabine-Cisplatin Plus Radical Cystectomy-Pelvic Lymph Node Dissection for Muscle-invasive Bladder Cancer: A 12-year Experience

IntroductionThe aim of this study was to determine drug delivery/toxicity, and pathologic/surgical outcomes of patients with muscle-invasive bladder cancer (MIBC) receiving neoadjuvant gemcitabine-cisplatin (GC) plus radical cystectomy-pelvic lymph node dissection (RC-PLND).Patients and MethodsChemotherapy and surgical/pathologic outcomes were retrospectively analyzed with 5-year survival follow-up at a referral center. Post-neoadjuvant chemotherapy (NAC) pathologic endpoints included complete response (pT0N0), residual non-MIBC (pTa/Tis/T1N0), and ≥ MIBC (≥ pT2 and/or N+). Associations of pathologic/surgical findings with overall survival (OS), disease-free survival (DFS), and surgical management with RC-PLND were analyzed (Cox regression).ResultsClinical T2a-T4aN0M0 MIBC patients (n = 154) from January 2000-October 2012 received GC plus RC-PLND. Patients (n = 117; 76%) received GC × 4 and 136 (88%) GC × 3. Five-year OS was 61% (95% confidence interval [CI], 53-71). Median number of resected lymph nodes (LNs) was 19. Down-staging was observed as follows: pT0N0: 21%; pTa/Tis/T1N0: 25%, with similar 5-year OS (85% and 89%, respectively). Five-year OS for < pT2 versus ≥ pT2 residual disease was 87% (95% CI, 78%-98%) versus 38% (95% CI, 27%-53%); P < .001. Post-NAC stage ≥ pT2 (HR, 6.79; 95% CI, 2.63-17.53; P < .001), positive LN (HR, 3.64; 95% CI, 1.84-7.19; P < .001), and positive margins (HR, 4.15; 95% CI, 1.68-10.25; P = .002) were associated with increased risk of all-cause death (multivariable analysis). An HR of 0.97 (95% CI, 0.94-1.00) was observed for each additional node removed, but this effect was not statistically significant (P = .056).ConclusionsNeoadjuvant GC achieves meaningful pathologic responses. Patients with ≥ pT2 residual disease, positive margins, or positive LN post-chemotherapy have inferior survival.     

Nomograms for Metastasis-Free and Overall Survival for Pathologically Node Positive Prostate Cancer Patients Treated With or Without Radiation Therapy Plus Short-Term ADT

Purpose/ObjectivesWe aimed to develop nomograms to predict the risk reduction for metastasis and death in pathologically node-positive (pN +) prostate cancer patients treated with or without radiation therapy (RT).Materials/MethodsFrom a prospectively gathered institutional database, we identified patients with pN + M0 prostate cancer after surgery. We evaluated several regression models of known or suspected clinical-pathologic covariates and selected the model with the highest Harrell's concordance-index (c-index) and clinical utility to prognosticate metastasis for inclusion in a nomogram. Covariates in the final, competing-risk adjusted, metastasis model included PSA nadir after surgery, pathologic T-stage, margin status, Gleason score (GS), number of positive lymph nodes, and use of postoperative radiotherapy combined with androgen deprivation therapy (RT + ADT). The overall survival model also included Charlson comorbidity score and age.Results336 pN + men with a mean age of 64.9 years and a median follow-up of 4.1 years who had a radical prostatectomy were included in the analysis. 83 men were recommended RT + ADT, of whom 4% refused the ADT and received RT alone. C-index was 0.85 and 0.71 for the MFS and OS models, respectively. On multivariable analysis (MVA) adjusted for competing risks, RT + ADT significantly improved MFS (HR=0.70 P = < .01) with number of nodes positive, GS 8-10, PSA nadir > 1 ng/mL, and pT3b prognostic for metastasis. MVA for OS demonstrates RT+ADT improves survival (HR=0.40, P = .02), with GS8-10 and PSA nadir > 1.0 prognostic for death.ConclusionWe developed predictive nomograms for patients with pN+ prostate cancer following radical prostatectomy. These models can discretely quantify an individual's risk of metastasis or death with and without post-prostatectomy radiotherapy.     

Impact of Lymphovascular Invasion on Overall Survival in Patients With Prostate Cancer Following Radical Prostatectomy: Stage-per-Stage Analysis

BackgroundThe detrimental impact of lymphovascular invasion (LVI) in prostate cancer (PCa) on biochemical recurrence has been described; the impact of LVI on overall survival (OS) remains unclear. This investigation sought to evaluate the impact of LVI on OS in patients with PCa.MethodsWe examined men with nonmetastatic PCa treated with radical prostatectomy between 2010 and 2015. Only men with documented LVI status were included (n = 232,704). Patients were stratified according to final pathologic T stage (pT2, pT3a, and pT3b).ResultsOf the 232,704 patients who met inclusion criteria, 17,758 (8%) were found to have LVI on final pathology. Overall, 174,838 (75%), 40,281 (17%), and 17,585 (8%) patients had pT2, pT3a, and pT3b disease, respectively. Median follow-up was 42.7 months (27.1-58.7). At 5 years, the OS in LVI versus non-LVI patients was 94% versus 95% in pT2 (P = .0004), 92% versus 95% in pT3a (P < .0001), and 86% versus 92% in pT3b (P < .0001). On multivariable analysis, LVI status was not an independent predictor of OS in pT2 disease (hazard ratio, 1.12; 95% confidence interval [CI], 0.93-1.36; P = .2). In pT3a and pT3b disease, presence of LVI had 1.2-fold (95% CI, 1.03-1.44; P = .02) and 1.4-fold (95% CI, 1.20-1.59; P < .001) higher overall mortality than their counterparts without LVI.ConclusionsOur report demonstrates the detrimental impact of LVI on OS in locally advanced PCa (pT3a and higher). This information may prove valuable when risk stratifying based on final pathology.     

Combining Adjuvant Radiotherapy With Capecitabine in Chemotherapy-resistant Breast Cancer: Feasibility,Safety, and Toxicity

BackgroundIn a randomized trial (CREATE-X), patients with residual disease after standard neoadjuvant chemotherapy had improved survival with the addition of adjuvant capecitabine. For patients who required radiotherapy (RT), capecitabine was given sequentially. Concurrent capecitabine-RT might be more efficacious. We hypothesized that the safety, feasibility, and toxicity of adjuvant capecitabine-RT would not be significantly different compared with adjuvant RT alone.Patient and MethodsWe retrospectively studied the data from patients with stage I-III invasive mammary carcinoma. Patients who had received capecitabine-RT were matched 1:3 with control patients who had received RT alone. Logistic regression analysis was used to evaluate the predictors of radiation dermatitis.ResultsA total of 64 patients were enrolled, including 16 who had received capecitabine-RT and 48 who had received RT alone. The cohorts were balanced regarding the clinicopathologic factors. No treatment in either cohort resulted in hospitalization, short-term disability, or fatality. Most toxicities of capecitabine-RT were related to radiation dermatitis. Radiation dermatitis was not significantly different between the capecitabine-RT and RT cohort at either grade 2 (odds ratio [OR], 1.36; 95% confidence interval [CI], 0.38-4.93; P = .63) or grade 3 (OR, 3.00; 95% CI, 0.85-10.63; P = .09) or after multivariable analysis. However, the capecitabine-RT group was more likely to require modifications in the RT schedule, including treatment breaks or cancelled fractions (44% vs. 17%; OR, 3.89; 95% CI, 1.12-13.52; P = .03).ConclusionCapecitabine-RT appears to be safe in the adjuvant treatment of breast cancer with comparable toxicity to RT alone. It might require more treatment adjustments. Prospective studies are needed to evaluate the safety and tolerability of this combination.     

Patient Risk Subgroups Predict Benefit of Adjuvant Chemotherapy in Stage II Rectal Cancer Patients Following Neoadjuvant Chemoradiation and Total Mesorectal Excision

BackgroundThe benefit of adjuvant chemotherapy (AC) is unclear in stage II (cT3-T4 N0) rectal adenocarcinoma (RAC) after neoadjuvant chemoradiation (NCRT) and total mesorectal excision (TME). We aim to identify pathologic factors that influence overall survival (OS) and stratify patients into risk profiles to assess the AC benefit within each profile.Patients and MethodsThe National Cancer Database for rectal cancer was utilized to identify patients with stage II RAC who completed NCRT and TME. Cox multivariable analysis was used to identify pathologic predictors of 5-year OS, which were then used to construct a nomogram and stratify patients into low-, intermediate-, and high-risk subgroups. Propensity score matching was applied for the receipt of AC within each risk stratum, and Kaplan–Meier analysis was used to measure 5-year OS.ResultsWe identified 3570 patients who met the inclusion criteria. Inadequate lymphadenectomy (<12), poor differentiation, involved distal margin, involved circumferential margin, perineural invasion, and absence of T-downstaging after NCRT were identified as unfavorable predictors of 5-year OS and were used to construct the nomogram. Kaplan–Meier analysis of the matched patients demonstrated the absolute 5-year survival benefits for each risk stratum as follows: 4% for low-risk patients (hazard ratio (HR) = 0.869; [0.651-1.021]; P = .062), 26% for intermediate-risk patients (HR, 0.249; [0.133-0.468]; P < .001), and 10% in high-risk patients (HR = 0.633 [0.427-0.940]; P = .024).ConclusionsThe survival benefit of AC for clinical stage II RAC following NCRT and TME is most pronounced among intermediate- and high-risk patients as determined by our nomogram. Risk-adaptive AC may be appropriate for selected patients by integrating standard reported pathologic elements into the treatment plan.     

Variation in Radiotherapy Referral and Treatment for High-risk Pathological Features after Radical Prostatectomy: Results from a Population-based Study

Aims

Guidelines recommend the discussion of adjuvant radiotherapy post-prostatectomy for prostate cancer patients with high-risk pathology to consider all of their treatment options. We determine whether patterns of radiotherapy referral and treatment post-prostatectomy reflect guideline-based use in a contemporary prostatectomy cohort.

Elevated serum carcinoembryonic antigen level after curative surgery is a prognostic biomarker of stage II-III colorectal cancer

BackgroundHigh preoperative carcinoembryonic antigen (CEA) is a well-known risk factor for stage II-III colorectal cancer (CRC); however, in most cases, cancer does not recur. Conversely, postoperative CEA (post-CEA) is occasionally measured, and high post-CEA patients often develop recurrence; however, the clinical significance of post-CEA testing is unknown. The purpose of this study was to determine whether post-CEA elevation might indicate a poor prognosis for stage II-III CRC patients who underwent curative surgery.Patients and methods482 patients with pathological stage II-III CRC were included. Univariate and multivariate analyses were performed to evaluate post-CEA levels.ResultsMultivariate analysis showed that elevated post-CEA (hazard ratio (HR): 3.14, P < 0.001), pathological lymph node metastasis (pN+), and pathological T4 (pT4) are associated with poor recurrence-free survival (RFS), and that elevated post-CEA (HR: 3.12; P = 0.002), pN+, pT4, age >70, and smoking are independently associated with poor overall survival. Subgroup analysis among stage III patients, in combination with the risk classification of the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) study, showed that elevated post-CEA is a significant indicator of poor prognosis for RFS in both low-risk (73.8% vs. 21.2%, P < 0.001) and high-risk (49.9% vs. 25.0%, P = 0.04) groups.ConclusionsPost-surgical CEA elevation is independently associated with poor prognosis in stage II-III CRC. Adding post-CEA levels to the IDEA risk classification may provide a more reliable indicator of the need for individualized surveillance and adjuvant chemotherapeutic strategies.     

Adjuvant radiotherapy for extremity and trunk wall atypical lipomatous tumor/well-differentiated LPS (ALT/WD-LPS): a French Sarcoma Group (GSF-GETO) study

BackgroundThe role of adjuvant radiotherapy (RT) in the management of atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WD-LPS) remains controversial.MethodsTwo hundred eighty-three patients with operable ALT/WD-LPS, no history of previous cancer, chemotherapy (CT) or RT, treated between 1984 and 2011 registered in the Conticabase database were included and described. Overall (OS), progression-free survival (PFS) and time to local relapse (TTLR) were evaluated from the time of first treatment.ResultsThree of 20 centers enrolled 58% of the patients. Median age at diagnosis was 61 (range 25–94) years, 147 patients (52%) were males, 222 (78%) patients had their primary tumor located in an extremity while 36 (13%) and 25 (9%) had tumors involving the girdle and the trunk wall, respectively. The median size of primary tumors was 17 cm (range 2–48 cm). Adjuvant RT was given to 132 patients (47%). Patients who received adjuvant RT had larger tumors (P = 0.005), involving more often the distal limbs (P < 0.001). Use of adjuvant RT varied across centers and along the study period. Other characteristics were balanced between the two groups. Median follow-up was 61.7 months. None of the patients developed metastasis during follow-up. The 5-year local relapse-free survival rates were 98.3% versus 80.3% with and without adjuvant RT, respectively (P < 0.001). Once stratified on time period (before/after 2003), adjuvant RT, tumor site and margin status (R0 versus other) were independently associated with TTLR. No OS difference was observed (P = 0.105).ConclusionIn this study, adjuvant RT following resection of ALT/WD-LPS was associated with a reduction of LR risk.     

Locoregional and Distant Outcomes in Women With cT1-3N1 Breast Cancer Treated With Neoadjuvant Chemotherapy With or Without Adjuvant Radiotherapy

BackgroundWe evaluated the impact of postmastectomy radiotherapy (PMRT) or supraclavicular radiation therapy (SCV RT) in women with cT1-3N1 breast cancer (BC) who became node negative (ypN0) after neoadjuvant chemotherapy (NAC).Patients and MethodsWe retrospectively reviewed 485 women treated with NAC for BC between 2005 and 2019. Radiation treatment fields were reviewed in detail. Pathologic complete response (pCR) was defined as ypT0/Tis ypN0. Patients who had residual nodal disease were defined as ypN+. Those who achieved complete response in the lymph nodes but not in the breast were defined as ypT+ypN0.ResultsAfter excluding patients with cT4 and cN0 disease at diagnosis, a total of 185 patients with cT1-3N1 BC were included. Patients were more likely to receive PMRT if they had ypN+ disease (P < .001) and/or lymphovascular invasion (P = .03). Patients who underwent lumpectomy were more likely to receive SCV RT if they did not achieve pCR (P = .04) and/or if they had ypN+ disease (P = .01). The 5-year rates of locoregional recurrence (LRR) were 15% for all patients, 14% for patients who attained ypT+ypN0, and 5% for patients who achieved pCR. Of ypT+ypN0 patients (n = 98), 53 received PMRT or SCV RT and 45 did not. For these patients, there were no differences in LRR based on whether a patient did or did not receive PMRT or SCV RT (P = .23).ConclusionRecommendations for or against PMRT or SCV RT after NAC vary based on final pathologic response. We await the results of ongoing randomized clinical trials to help guide clinical decision making in this context.