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.     

Efficacy of Neoadjuvant Chemohormonal Therapy in Oligometastatic Hormone-Sensitive Prostate Cancer: A Prospective,Three-Arm,Comparative Propensity Score Match Analysis

BackgroundThe study aimed to investigate the efficacy and safety outcomes in hormone-sensitive oligometastatic prostate cancer (OMPC) patients treated with docetaxel-based neoadjuvant chemohormonal therapy (NCHT) prior to radical prostatectomy (RP) compared with direct RP and standard androgen deprivation therapy (ADT) alone using propensity score match (PSM) analysis.Patients and MethodsA single-center, prospective, three-arm study was conducted with hormone-sensitive OMPC patients. Eligible patients (N = 130) were divided into three groups—NCHT, RP, and standard treatment (ST)—and received their respective treatments. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were pathological response rate, radiographic progression-free survival (rPFS), and overall survival (OS). Further, propensity scores were calculated and group-wise comparisons were carried out: NCHT versus RP, ST versus RP, and ST versus NCHT.ResultsAfter PSM, in the NCHT group, two patients (11.76%) and four patients (23.52%) had complete and partial pathological responses, respectively. Univariate and multivariate Cox regression analysis showed that PFS and rPFS were significantly higher in the NCHT group. For NCHT versus RP, the PFS hazard ratio (HR) = 0.11 (95% confidence interval [CI], 0.02-0.51; P = .004) and HR = 0.016 (95% CI, 0.0015-0.17; P < .001); the rPFS HR = 0.088 (95% CI, 0.011-0.71; P = .023) and HR = 0.03 (95% CI, 0.0025-0.36; P = .006). Further, the median OS of the ST group was 44.6 months for ST versus RP, and it was 49.3 months for ST versus NCHT; it was not reached in either the NCHT or RP group. Furthermore, 17.65% and 47.06% patients had positive surgical margins in the NCHT and RP groups, respectively, and no therapy-related deaths were observed during the study period.ConclusionsPSM analysis revealed NCHT before RP in OMPC patients has potential therapeutic benefits with acceptable toxicities and lower incidence of postoperative positive surgical margins.     

Survival Outcomes of Radical Prostatectomy Versus Radiotherapy in Intermediate-Risk Prostate Cancer: A NCDB Study

Background

Studies of various prostate cancer patient cohorts found men receiving external-beam radiotherapy (EBRT) had higher mortality than men undergoing radical prostatectomy (RP). Conversely, a recent clinical trial showed no survival differences between treatment groups. We used the National Cancer Data Base (NCDB) to evaluate overall survival in intermediate-risk (T2b-T2c or Gleason 7 [grade group II or III] or prostate-specific antigen 10-20 ng/mL) prostate cancer patients undergoing EBRT with or without androgen deprivation therapy (ADT), RP, or no initial treatment.

The Impact of Locoregional Treatment on Survival in Patients With Metastatic Breast Cancer: A National Cancer Database Analysis

BackgroundAlthough systemic therapy is the standard treatment for metastatic breast cancer, the value of locoregional treatment (LRT) of the primary tumor and its impact on survival is controversial. This study evaluates survival outcomes in patients with metastatic breast cancer after receiving LRT (surgery and/or radiation therapy) of the primary tumor.Materials and MethodsThe National Cancer Database was used to identify 16,128 qualifying cases of metastatic breast cancer who received systemic therapy with or without LRT from 2004 to 2013. Treatment modality was divided into surgery (Sx), radiation therapy (RT), surgery followed by RT (Sx + RT), and no LRT. The median survival and 3-year actuarial survival rates (OS) were analyzed for each treatment group. On multivariate analyses, adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were computed using Cox regression modeling to adjust for patient and clinicopathologic characteristics.ResultsOverall, the median follow-up was 28.3 months, and the median survival for all patients was 37.2 months. With 9761 deaths reported, the estimated 3-year OS was 51.3%. The Sx + RT group (n = 2166) had the highest 3-year OS of 69.4%, followed by the Sx group (n = 4293) with 57.6%, the no LRT group (n = 8955) with 44.3%, and the RT group (n = 714) with 41.5% (P < .0001). On multivariate analysis, compared with the no LRT group, a decreased HR was noted in patients receiving Sx (adjusted HR, 0.68; 95% CI, 0.65-0.71; P < .0001) and Sx + RT (adjusted HR, 0.46; 95% CI, 0.43-0.49; P < .0001).ConclusionLRT, especially surgery followed by RT, in addition to systemic therapy, was associated with improved survival in patients with metastatic breast cancer.     

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.     

Greatest Percentage of Involved Core Length and the Risk of Death From Prostate Cancer in Men With Highest Gleason Score ≥ 7

Introduction/BackgroundMen with highest GS ≥ 7 and a differing, lower GS core (ComboGS) have decreased PC-specific mortality (PCSM) risk after RT or RT and androgen deprivation therapy (ADT). Whether the greatest percentage of involved core length (GPC) modulates this risk is unknown.Patients and MethodsMen with GS ≥ 7 PC (n = 333) consecutively treated between December 1989 and July 2000 using RT (n = 268; 80%) or RT and 6 months of ADT (n = 65; 20%) comprised the study cohort. The GPC was calculated using biopsy core and tumor lengths. We used competing risks regression to assess whether increasing GPC was associated with increased PCSM risk in men with or without ComboGS adjusting for risk group, age, and treatment.ResultsAfter a median follow-up of 5.36 years (interquartile range, 3.22-7.61 years), 92 (28%) men died, 28 (30%) of PC. Increasing GPC was significantly associated with increased risk of PCSM (adjusted hazard ratio, 1.02; 95% confidence interval, 1.01-1.03; P = .005). Men with GPC ≥ 50% versus < 50% had significantly greater PCSM estimates when ComboGS was present (P < .001) versus absent (P = .55). Of the 127 men with ComboGS and GPC < 50%, 83% were treated with RT alone and 2 PC deaths were observed; neither in men with GS 7 and favorable intermediate-risk PC.ConclusionMen treated with RT for ComboGS, GPC < 50%, GS 7, and favorable intermediate-risk PC have a very low risk of early PCSM. The RTOG 0815 trial will establish whether ADT is necessary to optimize curability in these men.     

Metastasis,Mortality, and Quality of Life for Men With NCCN High and Very High Risk Localized Prostate Cancer After Surgical and/or Combined Modality Radiotherapy

PurposeTo compare metastasis-free survival, overall survival, and patient-reported quality of life (QOL) of men with National Comprehensive Cancer Network high or very high risk prostate cancer after definitive surgery and/or multimodal radiotherapy (RT).Patients and MethodsWe studied a retrospective cohort study of 586 patients treated between the years 2000 and 2017 receiving radical prostatectomy with or without postoperative RT, external-beam RT (EBRT) with androgen deprivation therapy (ADT), or EBRT plus brachytherapy (Brachy) boost + ADT. Patient-reported QOL for urinary, bowel, sexual, and overall physical and mental functioning was assessed using the American Urological Association symptom scale, the Sexual Health Inventory in Men, the Rectal-Function Assessment Scale, the Expanded Prostate Cancer Index Composite, and the Veterans RAND 12-Item Health Survey.ResultsMedian follow-up for survival was 5 years. No significant differences between the treatments were observed for overall survival or metastasis-free survival at the P < .05 threshold. The propensity-adjusted 5-year metastasis-free survival estimates for EBRT + ADT, EBRT + Brachy + ADT, and surgery were 74.6%, 94.8%, and 83.1%, respectively. The EBRT + Brachy + ADT and surgery cohorts had significantly worse mean American Urological Association symptom scores at 6 months than the EBRT + ADT cohort, which resolved by 1 year. Surgical patients had better rectal function scores than EBRT + ADT patients at years 1 to 3, but similar function thereafter. Adjuvant or salvage RT resulted in significant declines in various Expanded Prostate Cancer Index Composite urinary, sexual, and bowel domains, and Veterans RAND 12-Item Health Survey physical but not mental domains.ConclusionMen with very and/or high-risk localized prostate cancer are likely to require multimodal therapy. The overall differences in survival and long-term QOL are similar for men choosing surgical versus RT pathways.     

Propensity-Weighted Survival Analysis of SBRT vs. Conventional Radiotherapy in Unfavorable Intermediate-Risk Prostate Cancer

BackgroundProstate stereotactic body radiotherapy (SBRT), which delivers high-dose precision treatment in ≤5 fractions, is a shorter, more convenient, and less expensive alternative to conventionally fractionated radiotherapy (CRFT; ∼44 fractions) or moderately hypofractionated radiotherapy (MFRT; 20-28 fractions). SBRT has not been widely adopted but may have radiobiologic advantages over CFRT/MFRT. We hypothesized that SBRT would be associated with improved overall survival (OS) versus CFRT or MFRT ± androgen deprivation therapy (ADT) for unfavorable-intermediate-risk prostate cancer (UIR-PCa).MethodsMen with UIR-PCa treated with SBRT (35-40Gy in ≤5 fractions) or biologically equivalent doses of CFRT (72-86.4Gy in 1.8-2.0Gy/fraction) or MRFT (≥60Gy in 2.4-3.2Gy/fraction; biologically effective doses ≥120) were identified in the National Cancer Database (NCDB). Unweighted and propensity-weighted multivariable Cox analysis (MVA) was used to compare OS hazard ratios.ResultsOf 28,028 men with UIR-PCa who received CFRT with (n = 12,872) or without ADT (n = 12,984); MFRT with (n = 251) or without ADT (n = 281); and SBRT with (n = 212) or without ADT (n = 1,428) were identified. Relative to CFRT without ADT, CFRT+ ADT (HR 0.92, 95% CI 0.87-0.97, P = .002) and SBRT without ADT (HR 0.74, 95% CI 0.61-0.89, P = .002) were both associated with improved OS on MVA. Relative to CFRT+ADT, SBRT without ADT correlated with improved OS on MVA (HR:0.81, 95% CI 0.67-0.99, P = .04). Propensity-weighted MVA demonstrated that SBRT (HR:0.80, 95% CI 0.65-0.98, P = .036) and ADT (HR:0.91, 95% CI 0.86-0.97, P = .002) correlated with improved OS. SBRT was not associated with improved OS versus MFRT.ConclusionSBRT, which offers a cheaper and shorter treatment course that mitigates COVID-19 exposure, was associated with improved OS versus CFRT for UIR-PCa. These results confirm guideline-based recommendations that SBRT is a viable option for UIR prostate cancer. The results from this large retrospective study require further validation in clinical trials.     

Angiogenic and Antiangiogenic VEGFA Splice Variants in Colorectal Cancer: Prospective Retrospective Cohort Study in Patients Treated With Irinotecan-Based Chemotherapy and Bevacizumab

BackgroundAlternative splicing of vascular endothelial growth factor A (VEGFA) results in VEGFAxxxb antiangiogenic isoforms that fail to activate angiogenesis. Bevacizumab, widely used in patients with metastatic colorectal cancer (CRC), binds both VEGFA and VEGFAxxxb isoforms.Patients and MethodsFormalin-fixed, paraffin-embedded primary tumors from metastatic CRC patients treated with first-line FOLFIRI (leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin) + bevacizumab (n = 285) or FOLFIRI only (n = 75) were collected. The relative expression of VEGFA121a, 121b, 145a, 145b, 165a, and 165b was assessed with custom TaqMan-MGB assays and quantitative PCR.ResultsAt a median follow-up of 101.5 months, left-sided primary CRC was a favorable prognosticator (median survival, 29.2 vs. 18.2 months; P = .015). Positive high VEGFA145b was an unfavorable factor for progression-free survival (PFS; hazard ratio [HR] = 1.66; 95% confidence interval [CI], 1.13-2.44; P = .009) in patients who received FOLFIRI + bevacizumab, without prognostic significance in FOLFIRI-only patients (HR = 0.70; 95% CI, 0.34-1.44; P = .33). The adverse effect on PFS of 145b was more pronounced in patients with right-sided colon cancer (HR = 2.62; 95% CI, 1.35-5.12; P = .005), especially in those who received bevacizumab (HR = 2.85; 95% CI, 1.31-6.21; P = .008). In patients with right-sided colon primary tumors, isoform 121b correlated with inferior PFS (HR = 1.73; 95% CI, 0.94-3.18; P = .076) and overall survival (OS; HR = 2.0; 95% CI, 1.08-3.72; P = .028). In patients with left-sided primary tumors, positive high 165b correlated with superior PFS (HR = 0.76; 95% CI, 0.59-0.99; P = .044) and OS (HR = 0.68; 95% CI, 0.52-0.90; P = .006). At multivariate analysis, right-sided primary tumor was associated with inferior PFS (HR = 1.28; 95% CI, 1.00-1.64), while 145b consistently retained predictive significance for lack of benefit in PFS with bevacizumab (HR = 1.71; 95% CI, 1.16-2.53). Multivariate analysis for OS showed that VEGFA165b expression was favorable in patients with left-sided but unfavorable in patients with right-sided primary tumors (P_interaction < .001).ConclusionThe antiangiogenic isoform VEGFA145b messenger RNA may predict resistance to bevacizumab. Differences in biological relevance and prognostic significance of various VEGFA isoforms were found for right- versus left-sided primary tumors.     

Overall Survival After Treatment of Localized Prostate Cancer With Proton Beam Therapy,External-Beam Photon Therapy,or Brachytherapy

BackgroundThere are few comparative outcomes data regarding the therapeutic delivery of proton beam therapy (PBT) versus the more widely used photon-based external-beam radiation (EBRT) and brachytherapy (BT). We evaluated the impact of PBT on overall survival (OS) compared to EBRT or BT on patients with localized prostate cancer.Patients and MethodsThe National Cancer Data Base (NCDB) was queried for 2004-2015. Men with clinical stage T1-3, N0, M0 prostate cancer treated with radiation, without surgery or chemotherapy, were included. OS, the primary clinical outcome, was fit by Cox proportional hazard model. Propensity score matching was implemented for covariate balance.ResultsThere were 276,880 eligible patients with a median follow-up of 80.9 months. A total of 4900 (1.8%) received PBT, while 158,111 (57.1%) received EBRT and 113,869 (41.1%) BT. Compared to EBRT and BT, PBT patients were younger and were less likely to be in the high-risk group. On multivariable analysis, compared to PBT, men had worse OS after EBRT (adjusted hazard ratio [HR] = 1.72; 95% confidence interval [CI], 1.51-1.96) or BT (adjusted HR = 1.38; 95% CI, 1.21-1.58). After propensity score matching, the OS benefit of PBT remained significant compared to EBRT (HR = 1.64; 95% CI, 1.32-2.04) but not BT (adjusted HR = 1.18; 95% CI, 0.93-1.48). The improvement in OS with PBT was most prominent in men ≤ 65 years old with low-risk disease compared to other subgroups (interaction P < .001).ConclusionIn this national data set, PBT was associated with a significant OS benefit compared to EBRT, and with outcomes similar to BT. These results remain to be validated by ongoing prospective trials.     

Efficacy and Adverse Events of Docetaxel for Metastatic,Hormone-sensitive Prostate Cancer Among Elderly Men: A Post Hoc Analysis of the CHAARTED Trial

BackgroundCombination therapy with docetaxel and androgen deprivation therapy (ADT) prolongs overall survival (OS) in men with metastatic hormone-sensitive prostate cancer. We assessed the benefits and adverse effects of docetaxel and ADT in relation to advancing age.MethodsWe performed a post hoc analysis of the CHAARTED trial comparing docetaxel and ADT vs. ADT alone (n = 773). Patients were stratified in age groups <60, 60-70, and >70 years old. Multivariable-adjusted progression-free survival (PFS) and OS were assessed using Kaplan–Meier curves and compared using multivariable Cox regressions with calculated interaction terms between age group and treatment arm. In the combination arm, the incidence of ≥1 adverse event (grade ≥3) and the number of adverse events per patient were compared for each age group using multivariable logistic and linear regressions, respectively.ResultsAfter adjusting for clinical variables, docetaxel's effect did not vary by age group for PFS and OS. There was no significant difference in the odds ratio of ≥1 adverse event (P > .1 for age groups 60-70 and >70 years old compared with <60 years old). However, men age >70 years old experienced +0.37 more adverse events per patient compared with men age <60 years old (95% CI, 0.11-0.64; P = .006).ConclusionsPFS and OS were similar across age groups for the combination of docetaxel and ADT compared with ADT. Older men experienced a modest increase in adverse events per patient, highlighting the importance of balancing treatment benefits and adverse effects in this age group.     

The Significance of Lymph Node Ratio and Total Lymph Nodes Examined in Determining the Indications of Adjuvant Radiation in pN2 Non–small Cell Lung Cancer

Introduction/BackgroundPast studies have shown mixed results of postoperative radiation (PORT) for pN2 NSCLC patients. We hypothesize that PORT can improve overall survival (OS) in pN2 NSCLC patients with high lymph node ratio (LNR).Materials/MethodsThe National Cancer Database was queried for non-metastatic pN2 NSCLC patients with R0 surgery and adjuvant chemotherapy from 2004 to 2016. Cox models were used to assess the impact of PORT and LNR on OS adjusted for patient characteristics and treatment information.ResultsAmong 4,050 patients, 1,728 (42.7%) had PORT. There was increased use of IMRT in the more recent period (53.8% in 2010-2016 vs 24.0% in 2004-2009). PORT was associated with better OS in the overall cohort. For patients with inadequate lymph node dissection (LND), PORT marginally improved OS (HR = 0.91, p = 0.058). Among patients with adequate LND, PORT did not improve OS for patients with LNR <15% (HR = 1.11, p = 0.21), or LNR 15-29% (HR = 1.03, p = 0.73), but it significantly improved OS for patients with LNR ≥30% (HR = 0.83, p = 0.006). In patients with LNR≥30%, IMRT significantly improved OS when compared to no PORT (HR = 0.75, p < 0.05) while 3D RT did not (HR = 0.89, p = 0.32).ConclusionsPORT was associated with better survival for pN2 NSCLC patients after R0 resection, adequate LND with high LNR, after accounting for multiple confounders. Among the whole cohort, most of the OS benefits of PORT were driven by patients with inadequate LND, high LNR or use of IMRT.     

Impact of Metastasectomy on Cancer Specific and Overall Survival in Metastatic Renal Cell Carcinoma: Analysis of the REMARCC Registry

BackgroundTreatment paradigms for management of metastatic renal cell carcinoma (mRCC) are evolving. We examined impact of surgical metastasectomy on survival across in mRCC stratified by risk-group.MethodsMulticenter retrospective analysis from the Registry of Metastatic RCC database. The cohort was subdivided utilizing Motzer criteria (favorable-, intermediate-, high-risk). Primary outcome was all-cause mortality (ACM)/overall survival (OS); secondary outcome was cancer-specific mortality (CSM)/cancer-specific survival (CSS). Impact of metastasectomy was analyzed via Cox-Regression analysis adjusting for potential prognostic variables and Kaplan-Meier analysis (KMA) within each risk-group.ResultsFour hundred thirty-one patients (59 favorable-risk, 274 intermediate-risk, 98 high-risk; median follow-up 27.2 months) were analyzed. Metastasectomy was performed in 22 (37%), 66 (24%), and 32 (16%) of favorable-, intermediate- and high-risk groups (P = .012). Median number of metastases at diagnosis differed significantly (favorable-risk 2, intermediate-risk 3.4, high-risk 5.1, P < .001). On Cox-regression, high-risk (HR = 1.72, P = .002) was associated with worsened ACM, while metastasectomy was associated with improved ACM (HR = 0.56, P = .005). On KMA, median OS (months) was longer with metastasectomy in favorable- (92.7 vs. 25.8, P = .003) and intermediate-risk (26.3 vs. 20.1, P = .038), but not high-risk (P = .911) groups. Metastasectomy was associated with longer CSS in favorable- (76.1 vs. 32.8, P = .004) but not intermediate- (P = .06) and high-risk (P = .595) groups.ConclusionsMetastasectomy was independently associated with improved ACM and CSM, as well as improved CSS and OS in favorable- and intermediate-risk mRCC patients. Metastasectomy may be considered as component of multimodal management strategy in favorable and intermediate-risk subgroups. In high-risk patients, metastasectomy should be deferred except in select circumstances.     

Checkpoint Inhibitors in Metastatic EGFR-Mutated Non–Small Cell Lung Cancer—A Meta-Analysis

IntroductionWe performed a meta-analysis to assess the role of immune checkpoint inhibitors as second-line therapy in EGFR-mutant advanced NSCLC.MethodsRandomized trials comparing immune checkpoint inhibitors against chemotherapy were identified. We retrieved the hazard ratio (HR) and 95% confidence interval (CI) for overall survival (OS) of the intention-to-treat population and EGFR mutation–defined subgroups. We used the fixed-effects inverse variance–weighted method to pool estimates of treatment efficacy. Statistical tests were two sided.ResultsIn the three included studies that compared immune checkpoint inhibitors (nivolumab [n = 292], pembrolizumab [n = 691], and atezolizumab [n =144]) against docetaxel (n = 776), immune checkpoint inhibitors significantly prolonged OS over that with docetaxel overall (n = 1903, HR = 0.68, 95% CI: 0.61–0.77, p < 0.0001) and in the EGFR wild-type subgroup (n = 1362, HR = 0.66, 95% CI: 0.58–0.76, p < 0.0001) but not in the EGFR-mutant subgroup (n = 186, HR = 1.05, 95% CI: 0.70–1.55, p < 0.81; treatment-mutation interaction p = 0.03).ConclusionIn EGFR-mutant advanced NSCLC, immune checkpoint inhibitors do not improve OS over that with docetaxel. Mechanisms of acquired resistance to first-line tyrosine kinase inhibitor therapy should be elucidated to guide selection of second-line treatment for these patients.     

Survival of Patients With Second Primary Hodgkin Lymphoma

IntroductionThe increased risk for second malignancies after Hodgkin lymphoma (HL) diagnosis is well known. However, to our knowledge, no study has investigated the outcomes of patients diagnosed with HL after an antecedent malignancy (HL-2). We aimed to investigate overall survival (OS), disease-specific survival (DSS), and correlates of survival in HL-2 using the Surveillance, Epidemiology and End Results (SEER) database.Patients and MethodsHL-2 patients (n = 821) identified from the 2000-2014 SEER-18 registries were compared to first primary HL patients (HL-1, n = 31,355) from the same registries. Multivariable, propensity score–matched (PSM), and competing risks regression analyses were conducted to assess the effect of antecedent malignancy on survival.ResultsHematologic (n = 309, 37.6%), prostate (n = 169, 20.6%), and breast (n = 76, 9.3%) malignancies were common antecedent malignancies in HL-2. Median latency between antecedent malignancy and HL diagnosis was 39 months. Median ages at HL diagnosis for HL-1 and HL-2 were 36 and 66 years, respectively (P < .001). The 5-year OS and HL-DSS rates for HL-2 versus HL-1 were 53.2% versus 82.7% and 79.1% versus 90.9%, respectively (P < .001). On multivariable analysis, antecedent malignancy was associated with decreased OS (hazard ratio [HR] = 1.27; 95% confidence interval [CI], 1.13-1.42; P < .001). With PSM balancing across covariables, antecedent malignancy was associated with decrements in HL-DSS (HR = 1.46; 95% CI, 1.12-1.92; P = .006) and OS (HR = 2.09; 95% CI, 1.74-2.51; P < .001).ConclusionThe decrement in DSS in HL-2 relative to HL-1 may be related to biological differences in HL, age, and/or other unanalyzed factors. Further study of HL-2 patients is warranted.     

Relationship Between Metastasis-free Survival and Overall Survival in Patients With Nonmetastatic Castration-resistant Prostate Cancer

BackgroundMetastasis-free survival (MFS) has been shown to be predictive of overall survival (OS) in hormone-sensitive localized prostate cancer. We evaluated the relationship between MFS and OS in nonmetastatic castration-resistant prostate cancer (nmCRPC).Patients and MethodsA retrospective analysis of 1207 high-risk patients with nmCRPC from the SPARTAN study (clinicaltrials.gov, NCT01946204) was undertaken. Landmark analyses of MFS status at several time points from randomization were performed to minimize guarantee-time bias. Hazard ratio (HR) of death as a function of MFS status was estimated based on a Cox proportional hazards model with 2-sided 95% confidence interval (CI). Estimated HRs were adjusted for stratification factors. Correlation analysis was performed using the Fleischer method.ResultsAt all time points, MFS status strongly predicted OS. At landmark time points of 6, 9, and 12 months, risk of death was significantly higher for patients with metastases versus those without (adjusted HR at 6 months = 4.12; 95% CI, 2.60-6.54; P < .0001). MFS was positively correlated with OS based on the Fleischer method (HR, 0.69; 95% CI, 0.69-0.70; P < .0001). Approximately one-half of the variability in OS can be explained by MFS.ConclusionMetastasis development, regardless of time point, is associated with significantly greater risk of death in men with high-risk nmCRPC; hence, MFS is predictive of OS.     

Surgical Prognosis of Synchronous Multiple Primary Lung Cancer: Systematic Review and Meta-Analysis

BackgroundWe evaluated the long-term prognosis of synchronous multiple primary lung cancer (SMPLC) patients after surgical treatment and explored prognostic factors for overall survival (OS).Materials and MethodsA systematic review and meta-analysis was performed regarding the surgical prognosis of SMPLC. A literature search was performed using online databases. All studies were rigorously categorized following the 8th edition of the tumor, node, metastasis classification (TNM) staging rules for multiple lung cancers: SMPLC and multifocal ground-glass/lepidic (GG/L) lung cancers. Five-year OS after surgery was pooled, and hazard ratios (HRs) for prognostic factors were synthesized. Specific subgroup analysis and sensitivity analysis were conducted (PROSPERO registration CRD42019142420).ResultsAn analysis of 26 studies including 1788 patients was performed. The pooled 5-year OS was 45% (95% confidence interval [CI], 37-53) of true SMPLC patients and 62% (95% CI, 57-67) of patients with pathologic stage I disease, which was different from the 5-year OS of 93% (95% CI, 85-100) of patients with multifocal GG/L lung cancers. Poor prognostic factors for SMPLC were lymph node metastasis (HR = 2.36; 95% CI, 1.75-3.20; P < .001) and pneumonectomy (HR = 2.96; 95% CI, 1.36-6.45; P = .006], whereas histology (HR = 1.11; 95% CI, 0.82-1.50; P = .508), laterality (HR = 1.16; 95% CI, 0.93-1.44, P = .190), sublobar resection (HR = 1.29; 95% CI, 0.90-1.84; P = .159), and adjuvant therapy (HR = 1.07; 95% CI, 0.64-1.80; P = .791) were not found to influence the outcome.ConclusionThe long-term prognosis of SMPLC patients after surgery is acceptable, especially in patients with early-stage disease. Sublobar resection can be applied, although pneumonectomy should be avoided. Advanced criteria are needed to diagnose SMPLC and distinguish it from multifocal GG/L lung cancer to perform accurate surgical evaluation.     

Prognostic Role of Low-Skeletal Muscle Mass on Staging Computed Tomography in Metastasized Colorectal Cancer: A Systematic Review and Meta-Analysis

BackgroundLow-skeletal muscle mass (LSMM) is defined as skeletal muscle loss, which can be assessed by imaging. Our aim was to establish the effect of LSMM on overall survival (OS) in metastasized colorectal cancer patients based on a large patient sample.Patients and MethodsMEDLINE library, EMBASE, and SCOPUS databases were screened for the associations between LSMM and mortality in metastasized colorectal cancer patients up to March 2022. The primary aim of the systematic review was to investigate the influence of LSMM on overall survival (OS) by means of the effect of measure hazard ratio. Fifteen studies were included into the present analysis.ResultsThe included studies comprised 1744 patients. The frequency of LSMM was 46.2%. Associations between LSMM and OS were as follows: hazard ratio (HR) = 1.34 (95% confidence interval [CI] 0.94-1.91), P = .10 in univariable analysis and HR = 2.05 (95% CI 1.18-3.56), P = .01 in multivariable analysis. LSMM influenced OS in patients undergoing first-line chemotherapy, HR = 1.51 (95% CI 1.20-1.89), P = .0004. In patients undergoing second- and third-line chemotherapy, LSMM was not associated with OS, HR = 1.43 (95% CI 0.65-3.14), P = .37 Also, LSMM did not affect OS in patients with resection of hepatic metastases, HR = 0.93 (95% CI 0.70-1.24), P = .63. LSMM tended to affect progression-free survival, HR = 1.49 (95% CI 0.94-2.35), P = .09. LSMM did not predict treatment toxicity, odds ratio (OR) = 1.52 (95% CI 0.84-2.72), P = .16.ConclusionLSMM occurs in 46.2% of patients with metastasized colorectal cancers. LSMM is associated with OS in patients undergoing first-line chemotherapy. LSMM does not affect OS in second- and third-line chemotherapy and in patients undergoing resection of hepatic metastases. LSMM is not associated with progression-free survival and treatment toxicity.     

Diabetes and the Prognosis in Patients With Non-Hodgkin Lymphoma: A Meta-analysis of Cohort Studies

BackgroundConsensus lacks regarding the association between diabetes mellitus (DM) and the prognosis of patients with non-Hodgkin lymphoma (NHL). We aimed to systematically evaluate the above association, as well as the potential influence of metformin use in a meta-analysis of cohort studies.Materials and MethodsCohort studies investigating the association between DM and survival outcomes of patients with NHL were included by search of electronic databases that included PubMed, Embase, and Web of Science. A random-effects model was adopted to combine the results.ResultsEight cohort studies including 8652 patients with NHL were analyzed. Compared to non-DM patients with NHL, DM was associated with poor overall survival (OS, hazard ratio [HR] = 1.49, 95% confidence interval [CI]: 1.18-1.89, P < .001, I² = 69%), progression-free survival (PFS, HR = 1.30, 95% CI: 1.09-1.56, P = .004, I² = 0%), and lymphoma-specific survival (LSS, HR = 1.86, 95% CI: 1.41-2.45, P < .001, I² = 0%). Subgroup analysis showed consistent results in patients with diffuse large B-cell lymphoma (DLBCL, HR = 1.42, 1.35, and 1.95 for outcomes of OS, PFS, and LSS, respectively; P values all <.05). However, the associations between DM and these survival outcomes became nonsignificant in subgroup analysis limited to DM patients with concurrent use of metformin (HR = 1.30, 1.12, and 1.43 for outcomes of OS, PFS, and LSS, respectively; P values all > .10).ConclusionsDM is associated with poor survival outcomes in patients with B-cell NHL, which is consistent in patients with DLBCL. Concurrent metformin use in DM patients with NHL may be associated with improved survival outcomes.     

Neutrophil-to-lymphocyte ratio as a prognostic biomarker for men with metastatic castration-resistant prostate cancer receiving first-line chemotherapy: data from two randomized phase III trials

The derived neutrophil-to-lymphocyte ratio (dNLR) was prognostic for survival in men with metastatic castration-resistant prostate cancer receiving first-line chemotherapy in two randomized phase III trials. A high dNLR (≥2) was associated with shorter survival irrespective of the received treatment. This readily available biomarker may serve for risk stratification in future clinical trials.BackgroundThe neutrophil-to-lymphocyte ratio (NLR), a marker of host inflammation, has been associated with poor outcome in several solid tumors. Here, we investigated associations of the derived NLR (dNLR) and duration of initial androgen deprivation therapy (ADT) with survival of men with metastatic castration-resistant prostate cancer (mCRPC) receiving first-line chemotherapy.Patients and methodsData from the multinational randomized phase III studies VENICE and TAX327 included a total of 2230 men with mCRPC randomized to receive first-line chemotherapy, and were used as training and validation sets, respectively. Associations of dNLR and duration of initial ADT with overall survival (OS) were evaluated by multivariable Cox regression analysis in the training set stratified for performance status and treatment arm. The model was then tested in the validation set. Subsequently, we investigated the treatment effect of docetaxel on OS in subgroups according to dNLR and duration of initial ADT.ResultsIn the training set, both dNLR ≥median (2) and duration of initial ADT <median (15 months) were associated with increased risk of death [hazard ratio (HR) 1.29; 95% confidence interval (CI) 1.11–1.50,P < 0.001 and HR 1.41; 95% CI 1.21–1.64,P < 0.001, respectively] after adjustment for age, alkaline phosphatase, hemoglobin, and pain at baseline. In the validation set, dNLR remained an independent prognostic factor for OS (HR 1.43; 95% CI 1.20–1.70,P < 0.001), whereas duration of initial ADT was not (HR 1.16; 95% CI 0.97–1.37,P = 0.10). In subgroup analyses of the TAX327 study, docetaxel improved OS irrespective of dNLR and duration of initial ADT.ConclusionThe dNLR was prognostic for OS in men with mCRPC receiving first-line chemotherapy in two randomized phase III trials. A high dNLR (≥2) was associated with shorter survival irrespective of the received treatment. This readily available biomarker may serve for risk stratification in future clinical trials and could be incorporated into prognostic nomograms.Clinical Trials numberNCT00519285.