Contemporary conditional cancer-specific survival rates in surgically treated nonmetastatic primary urethral carcinoma.

BACKGROUND: We examined the effect of disease-free interval (DFI) duration on cancer-specific mortality (CSM)-free survival, otherwise known as the effect of conditional survival, in radical urethrectomy nonmetastatic primary urethral carcinoma (PUC) patients. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database 2000-2020, patient (age, sex, race/ethnicity, and marital status) and tumor (stage and histology) characteristics, as well as systemic therapy exposure status of nonmetastatic PUC patients were tabulated. Conditional survival estimates at 5-year were assessed based on DFI duration and according to stage at presentation (T1 -2N0 vs. T3-4N0-2). RESULTS: Of all 512 radical urethrectomy PUC patients, 278 (54%) harbored T1-2N0 stage versus 234 (46%) harbored T3-4N0-2 stage. In 512 PUC patients, 5-year CSM-free survival at initial diagnosis was 61.8%. Provided a DFI duration of 36 months, 5-year CSM-free survival was 85.6%. In 278 T1-2N0 PUC patients, 5-year CSM-free survival at initial diagnosis was 68.4%. Provided a DFI duration of 36 months, 5-year CSM-free survival was 86.9%. In 234 T3-4N0-2 PUC patients, 5-year CSM-free survival at initial diagnosis was 53.8%. Provided a DFI duration of 36 months, 5-year CSM-free survival was 83.6%. CONCLUSIONS: Although intuitively, clinicians and patients are well aware of the concept that increasing DFI duration improves survival probability, only a few clinicians can accurately estimate the magnitude of survival improvement, as was done within the current study. Such information is crucial to survivors, especially in those diagnosed with rare malignancies, where the survival estimation according to DFI duration is even more challenging.

Targeted Next-Generation Sequencing Reveals Exceptionally High Rates of Molecular Driver Mutations in Never-Smokers With Lung Adenocarcinoma.

INTRODUCTION: Historically, high rates of actionable driver mutations have been reported in never-smokers with lung adenocarcinoma (ADC). In the era of modern, comprehensive cancer mutation sequencing, this relationship necessitates a more detailed analysis. METHODS: All Mount Sinai patients between January 1, 2015, and June 1, 2020, with a diagnosis of ADC of any stage with known smoking status who received genomic testing were included. Most patients were analyzed using the Sema4 hotspot panel or the Oncomine Comprehensive Assay version 3 next-generation sequencing (NGS) panel conducted at Sema4. Patients were considered fully genotyped if they were comprehensively analyzed for alterations in EGFR, KRAS, MET, ALK, RET, ROS1, BRAF, NTRK1-3, and ERBB2, otherwise they were considered partially genotyped. RESULTS: Two hundred and thirty-six never-smokers and 671 smokers met the above criteria. Of the never-smokers, 201 (85%) had a driver mutation with 167 (71%) considered actionable (ie, those with US Food and Drug Administration-approved agents). Among smokers, 439 (65%) had an identified driver mutation with 258 (38%) actionable (P < .0001). When comprehensively sequenced, 95% (70/74) of never-smokers had a driver mutation with 78% (58/74) actionable; whereas, for smokers, 75% (135/180) had a driver with only 47% (74/180) actionable (P < .0001). Within mutations groups, EGFR G719X and KRAS G12Cs were more common to smokers. For stage IV patients harboring EGFR-mutant tumors treated with EGFR-directed therapies, never-smokers had significantly improved OS compared to smokers (hazard ratio = 2.71; P = .025). In multivariable analysis, Asian ancestry and female sex remained significant predictors of (1) OS in stage IV patients and (2) likelihood of harboring a receptor of fusion-based driver. CONCLUSION: Comprehensive NGS revealed driver alterations in 95% of never-smokers, with the majority having an associated therapy available. All efforts should be exhausted to identify or rule out the presence of an actionable driver mutation in all metastatic lung ADC.

Other-Cause Mortality, According to Partial vs. Radical Nephrectomy: Age and Stage Analyses.

INTRODUCTION: We tested the association between other-cause mortality and partial vs. radical nephrectomy in patients with T1a, T1b, and T2 renal cell carcinoma, across all patient ages. MATERIAL AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2010-2020), patients with localized renal cell carcinoma stages (T1a-T1b-T2, N0, M0), who underwent partial or radical nephrectomy were identified. Only patients with tumor size 2 to 10 cm were included. Cumulative incidence plots and multivariable competing risks regression models were used. RESULTS: Of 68,195 patients, 28,845 (42%) underwent partial nephrectomy vs. 39,350 (58%) radical nephrectomy. In T1a patients, 5-year other-cause mortality rates were 6% for partial nephrectomy vs. 11% for radical nephrectomy (Δ=5%). In T1a patients, partial nephrectomy independently predicted lower other-cause mortality, across all ages (HR: 0.73, P < .001). In age category subgroup analyses addressing T1a patients, in all age categories, partial nephrectomy invariably predicted lower other-cause mortality than radical nephrectomy: ≤59 years (HR: 0.67, P < .001); 60 to 69 years (HR: 0.70, P < .001); and ≥70 years (HR: 0.79, P < .001). Finally, in T1b patients, as well as in T2 patients, no other-cause mortality advantage was recorded for partial vs. radical nephrectomy: T1b (8 vs. 10%, Δ=2%); T2 (8 vs. 9%, Δ=1%). CONCLUSIONS: Relative to radical nephrectomy, partial nephrectomy is associated with lower other-cause mortality in stage T1a renal cell carcinoma patients across all age categories, including the oldest patients. Conversely, no clinically meaningful other-cause mortality benefit was associated with partial nephrectomy in stages T1b or T2, regardless of age, including youngest patients.

Contemporary sex-specific analysis of the association of marital status with cancer-specific mortality in primary urethral carcinoma patients.

BACKGROUND: It is unknown whether married status may be associated with lower cancer-specific mortality (CSM) rates in primary urethral carcinoma (PUC) patients. To test for differences in CSM rates, according to marital status, we relied on the Surveillance, Epidemiology, and End Results (SEER) database 2000-2020. METHODS: Patient (age, sex, race/ethnicity, marital status), tumor (stage, histology), and treatment (surgery, systemic therapy) characteristics of PUC patients were tabulated. Then, Kaplan-Meier plots, as well as univariable and multivariable Cox regression (MCR) models tested for differences in CSM rates according to marital status in overall cohort and then in sex-specific subgroup analyses. RESULTS: Of all 1,571 PUC patients, 70% were male vs. 30% female. Females were statistically significantly younger (68 vs. 73 years), more frequently unmarried (54 vs. 28%), non-Caucasian (43 vs. 24%), more frequently harbored T3-4N0M0 (39 vs. 18%) and less frequently T1-2N0M0 (53 vs. 69%) or TanyN1-2M0/TanyNanyM1 (8 vs. 13%), relative to males. Moreover, we recorded differences in histotype proportions in females vs. males (urothelial 30 vs. 64%; squamous 24 vs. 22%; adenocarcinoma 36 vs. 7%; others 10 vs. 6%) and surgical treatment (none 22 vs. 17%; excisional biopsy 22 vs. 36%; partial urethrectomy 14 vs. 16%; radical urethrectomy 42 vs. 31%). In MCR models focusing on the entire cohort, married status independently predicted lower CSM (hazard ratio [HR]:0.82; P = 0.02). Similarly, in MCR models focusing on females, married status independently predicted lower CSM (HR:0.73; P = 0.03). Conversely, in MCR models focusing on males, married status failed to independently predict lower CSM (HR:0.89; P = 0.3). CONCLUSIONS: Married status was associated with lower CSM in PUC patients. However, this benefit applies to female PUC patients, but not to their male counterparts.

Transcriptional subtypes of glottic cancer characterized by differential activation of canonical oncogenic programming.

BACKGROUND: There is a paucity of data concerning molecular heterogeneity among glottic squamous cell carcinoma, and the clinical implications thereof. METHODS: Data corresponding to glottic squamous cell carcinoma were derived from The Cancer Genome Atlas. The Onco-GPS computational methodology was levied to derive four patterns of transcriptional activity and three functional subtypes of glottic cancer. RESULTS: Thirty glottic cancer samples stratified to three distinct oncogenic states (S0-S2) based on a Onco-GPS model containing four transcriptional components (F0-F3). Membership in S2 and association with transcriptional component F0 conveyed an invasive phenotype, with transcriptional activity strongly reflecting EMT programming (including TGF-B and NF-KB signaling). S2 membership also correlated with inferior disease-specific survival (HR 9.027, 95% CI 1.021-79.767), and higher incidences of extracapsular spread and perineural invasion. CONCLUSIONS: We present a functional taxonomy of glottic cancer, with subtypes demonstrating differential upregulation of canonical oncogenic networks and survival implications.

Potential gain in life years for Swedish women with breast cancer if stage and survival differences between education groups could be eliminated - Three what-if scenarios.

Many studies have found evidence of socioeconomic differences in breast cancer survival. This study aimed to quantify the impact of removing differences in stage distribution and stage-specific relative survival between education groups in Swedish women with breast cancer. Using information from a breast cancer research database, the study population contained 62 121 women diagnosed with breast cancer in three healthcare regions of Sweden from 1992 to 2012. The loss in expectation of life and life years lost due to breast cancer were estimated using flexible parametric relative survival models by education group and age at diagnosis. The potential gain in life years and postponable deaths were calculated by applying the 1) stage distribution, 2) stage-specific relative survival, and 3) both stage distribution and stage-specific relative survival of the high education group to the low and medium education groups. For a cohort of around 3500 women diagnosed with breast cancer residing in three Swedish healthcare regions in a typical calendar year, we estimated that removing stage differences would postpone an additional 25 deaths at five years after diagnosis, and result in a gain of approximately 573 life years. Alternatively, if stage-specific breast cancer survival could be equated, approximately 692 life years could be saved and an additional 26 deaths could be postponed five years after diagnosis. Results such as these can help guide decisions on interventions intended to minimise socioeconomic differences in breast cancer outcomes.