De novo versus recurrent metastatic breast cancer affects the extent of brain metastases.

PURPOSE: We aimed to identify factors associated with the extent of brain metastases in patients with breast cancer to help distinguish brain oligometastases (1-4 brain metastases) from extensive metastases (5 or more brain metastases). METHODS: This retrospective observational study included 100 female patients diagnosed with brain metastases from breast cancer at a single institution between January 2011 and April 2022. Patient demographics and tumor characteristics were compared between the brain oligometastases group and the extensive metastases group. Multivariable logistic regression analysis was performed to determine the independent factors, including age at initial diagnosis, initial stage, breast cancer subtype, detection time of brain metastases, and de novo or recurrent status of the metastatic disease. In a subgroup analysis of patients with brain oligometastases, demographic and tumor characteristics were compared between patients with single and two-four brain metastases. RESULTS: Of the 100 patients, 56 had brain oligometastases, while 44 had extensive brain metastases. The multivariable logistic regression analysis revealed that only the de novo/recurrent status of metastatic breast cancer was significantly associated with the extent of brain metastasis (p = 0.023). In the subgroup analysis of 56 patients with brain oligometastases, those diagnosed at an earlier stage were more likely to have a single brain metastasis (p = 0.008). CONCLUSION: Patients with de novo metastatic breast cancer are more likely to develop extensive brain metastases than those with recurrent metastatic breast cancer. This insight could influence the development of tailored approaches for monitoring and treating brain metastases, supporting the potential advantages of routine brain screening for patients newly diagnosed with stage IV breast cancer.

Real-World Impact of Adjuvant Anti-HER2 Treatment on Characteristics and Outcomes of Women With HER2-Positive Metastatic Breast Cancer in the ESME Program.

BACKGROUND: Although adjuvant cancer treatments increase cure rates, they may induce clonal selection and tumor resistance. Information still lacks as whether (neo)adjuvant anti-HER2 treatments impact the patterns of recurrence and outcomes of HER2-positive (HER2+) metastatic breast cancer (MBC). We aimed to assess this in the large multicenter ESME real-world database. PATIENTS AND METHODS: We examined the characteristics and outcomes (overall survival (OS) and progression-free survival under first-line treatment (PFS1)) of HER2+ patients with MBC from the French ESME program with recurrent disease, as a function of the previous receipt of adjuvant trastuzumab. Multivariable analyses used Cox models adjusted for baseline demographic, prognostic factors, adjuvant treatment received, and disease-free interval. RESULTS: Two thousand one hundred and forty-three patients who entered the ESME cohort between 2008 and 2017 had a recurrent HER2+ MBC. Among them, 56% had received (neo)adjuvant trastuzumab and 2.5% another anti-HER2 in this setting. Patients pre-exposed to trastuzumab were younger, had a lower disease-free interval, more HR-negative disease and more metastatic sites. While the crude median OS appeared inferior in patients exposed to adjuvant trastuzumab, as compared to those who did not (37.2 (95%CI 34.4-40.3) versus 53.5 months (95% CI: 47.6-60.1)), this difference disappeared in the multivariable model (HR = 1.05, 95%CI 0.91-1.22). The same figures were observed for PFS1. CONCLUSIONS: Among patients with relapsed HER2+ MBC, the receipt of adjuvant trastuzumab did not independently predict for worse outcomes when adjusted to other prognostic factors.

Does definitive local therapy have a role in select HER2+ de novo metastatic breast cancer patients treated with dual anti-HER2 blockade?

PURPOSE: The role of surgery with curative intent in HER2+ de novo metastatic breast cancer (dnMBC) is uncertain in the era of dual antibody therapy. We sought to determine from existing retrospective data current practice patterns and if an association exists between surgery to the primary tumor and improved survival in HER2+ dnMBC patients treated with dual anti-HER2 blockade, accounting for selection bias. METHODS: This study employed data from the National Cancer Database (NCDB) from the years 2013 to 2015. Study inclusion was limited to adult women with HER2+ dnMBC, who received immunotherapy/biologic response modifier drugs (BRM) as a first line treatment. Patients who received both systemic therapy and surgery to the primary breast tumor and patients who received systemic therapy alone were analyzed in two groups. Chi-square test for discrete variables and Wilcox on Rank-Sum test for numeric variables was used to compare the two groups based on patient, tumor, and treatment characteristics. The primary endpoint was overall survival from the time of diagnosis to the time of death. RESULTS: 928 women with HER2+ dnMBC treated with BRM were identified with 43.5% (n = 404) receiving surgery and 56.5% (n = 524) receiving systemic therapy alone. The 3-year overall survival was superior for the surgery group (74.1%, 95% CI 67.9-79.2%) compared to the no surgery group (53.3%; 95% CI 47.6-58.6%). The no surgery group had median overall survival of 39.8 months (95% CI 34.1-44.9), while the surgery group had not yet reached median overall survival. CONCLUSION: In a group of HER2+ dnMBC patients receiving systemic treatment in the era of dual antibody therapy, patients who underwent surgery had a superior 3-year survival rate than those who did not. There may be a role for a prospective trial in HER2+ dnMBC patients with an excellent response to dual HER2 blockade to investigate the contribution of curative intent local therapy to the primary tumor compared to systemic therapy alone.

Impact of socioeconomic status and rurality on cancer-specific survival among women with de novo metastatic breast cancer by race/ethnicity.

PURPOSE: There are approximately 150,000 women living with metastatic breast cancer (mBC) in the United States. Disparities in de novo mBC incidence and mortality exist across race/ethnicity, socioeconomic status (SES), and rurality. However, how SES and rurality independently impact mBC outcomes across different racial/ethnic groups is not fully understood. The purpose of this study was to determine the impact of SES and rurality on cancer-specific mortality among women with mBC by race/ethnicity. METHODS: We conducted a large, population-based retrospective cohort study in women aged 18 + years diagnosed with de novo mBC using the Surveillance, Epidemiology and End Results Census Tract-level SES and Rurality Database (2000-2015). Associations between SES/rurality and cancer-specific mortality were determined using Fine and Gray regression models. Subdistribution hazard ratios (SHR) and 95% confidence intervals (CI) by race/ethnicity and hormone receptor (HR) status were calculated. RESULTS: A cohort of 33,976 women were included with the majority being White (67%), 17% Black, 0.4% American Indian/Alaskan Native, 6% Asian/Pacific Islander, and 10% Latina/Hispanic. We observed the greatest increased risk of BC mortality among Black women with HR-negative mBC residing in neighborhoods with lower SES (lowest versus highest quintile: SHR 1.38, 95% CI 1.00-1.90) and in rural areas compared to urban areas (SHR 1.27, 95% CI 1.01-1.59). CONCLUSION: Overall, BC-specific survival among women with de novo mBC differs by race/ethnicity, with the greatest adverse impacts of SES and rurality affecting Black women with HR-negative disease.

Clinical subtype, treatment response, and survival in De Novo and recurrent metastatic breast cancer.

PURPOSE: This study evaluated whether patients with de novo metastatic breast cancer (MBC) have superior outcomes compared to those with recurrent MBC in a contemporary treatment era and examined factors related to outcome differentials. METHODS: Using an institutional database, we examined patient and tumor characteristics, treatment response, and outcome among 232 patients with de novo and 612 patients with recurrent MBC diagnosed between 2011 and 2017. RESULTS: De novo MBC had 9-month (m) longer overall survival (OS) than recurrent MBC (36.4 vs 27.4 m, p < 0.001). Contributions to this difference included nearly twofold more HER2-positive (29.3% vs 15.2%) and significantly fewer triple-negative breast cancers (20.3% vs 32.4%, both p < 0.001) in de novo compared with recurrent MBC cohorts. Stratified by clinical subtype, progression-free survival (PFS) on first-line therapy was significantly longer in de novo MBC in all but the triple-negative subtype, 25.5 vs 11.6 m (p < 0.001) among 390 patients with hormone receptor-positive, HER2-negative, 11.4 vs 5.4 m (p = 0.002) among 142 patients with HER2-positive, and 4.0 vs 3.0 m (p = 0.121) among 162 with triple-negative MBC. In multivariable analysis, de novo status remained independently associated with improved OS (hazard ratio 0.63, 95% CI 0.49-0.80), regardless of subtype and other features. CONCLUSION: Patients with de novo MBC have better outcomes than those with recurrent MBC. Differences in clinical subtype and response to therapy in the metastatic setting contribute to, but do not fully explain, this difference. Longer PFS to first-line therapy in de novo MBC suggests biologic differences compared to recurrent MBC, which may be intrinsic or due to acquired resistance from treatment for prior localized breast cancer in recurrent disease.

Genomic profiles and clinical outcomes in primary versus secondary metastatic hormone-sensitive prostate cancer.

BACKGROUND: Clinical outcomes may differ among patients presenting with primary (de novo) metastatic hormone-sensitive prostate cancer (mHSPC) versus secondary (metachronous) mHSPC occurring after local therapy. It is unknown what molecular features distinguish these potentially distinct presentations. METHODS: A single-center retrospective study of mHSPC patients classified as primary mHSPC (n = 121) or secondary mHSPC (n = 106). A targeted set of genes was analyzed: BRCA2, PTEN, RB1, TP53, SPOP, CDK12, any two out of PTEN/RB1/TP53 alterations, and homologous recombination deficiency mutations. TP53 mutations were categorized as loss-of-function (LOF) versus dominant-negative (DN). The impacts of genetic features on progression-free survival (PFS) and overall survival (OS) were assessed using univariate and multivariate Cox proportional hazards regression. RESULTS: Median PFS was 15 and 30 months for men with primary and secondary mHSPC, respectively (hazard ratio: 0.57, 95% confidence interval: 0.41-0.78; p < .01). OS did not show a significant difference between groups. There were more men with Gleason 8-10 disease in the primary versus secondary mHSPC groups (83% vs. 68%; p < .01). In univariate and multivariate analyses, TP53 DN mutations showed a statistically significant association with OS for the entire mHSPC population. Conversely, SPOP mutations were associated with improved OS. Additionally, TP53 mutations (DN and LOF) were associated with worse OS for secondary mHSPC. A combination of PTEN/RB1/TP53 mutations was associated with worse OS and PFS for secondary mHSPC, while no genomic alteration affected outcomes for primary mHSPC. CONCLUSIONS: TP53 DN mutations, but not all TP53 alterations, were the strongest predictor of negative outcomes in men with mHSPC, while SPOP mutations were associated with improved outcomes. In subgroup analyses, specific alterations were prognostic of outcomes in secondary, but not primary, mHSPC.

Prognostic Value of Germline DNA Repair Gene Mutations in De Novo Metastatic and Castration-Sensitive Prostate Cancer.

BACKGROUND: Germline DNA damage repair gene mutations (gDDRm) have been found in approximately 12% of patients with metastatic prostate cancer (mPCa). Previous studies of the clinical impact of gDDRm have mainly been in the setting of metastatic castration-resistant prostate cancer (mCRPC). This study aimed to determine the prognostic value of gDDRm in de novo metastatic and castration-sensitive prostate cancer (mCSPC). MATERIALS AND METHODS: We retrospectively collected the records of 139 consecutive men with de novo mCSPC who initially received systemic therapies following guidelines. This included 128 patients who underwent genetic testing at our center and 11 patients referred to our center after being identified as gDDRm carriers. Time to mCRPC was collected. Kaplan-Meier and log-rank analysis were used to analyze the association between gDDRm and clinical outcomes. Survival outcomes were adjusted using multivariable Cox regression models. RESULTS: Of the 139 patients with de novo mCSPC, 28 gDDRm carriers were identified. Median time progressing to mCRPC was significantly shorter in patients carrying gDDRm than in those without mutations (8.3 vs 13.2 months; hazard ratio [HR], 2.37; p < .001). Moreover, median progression time was almost halved in BRCA2 carriers (6.3 vs. 13.2 months; HR, 3.73; p < .001). Subgroup analysis revealed that the presence of gDDRm indicated poor therapy response regardless of disease volume and prostate-specific antigen nadir within the first 7 months. Presence of gDDRm remained independently associated with increased risk of progression to mCRPC in multivariate analysis (adjusted HR, 1.98; p = .006). CONCLUSION: Our study suggested that positive gDDRm status predicted rapid progression to castration resistance in patients with de novo mCSPC. We propose identifying gDDRm status at the time of diagnosis for mCSPC patients, considering it is the first step of tailoring individualized treatment. In addition, DNA repair genes were a good therapeutic target for poly (ADP-ribose) polymerase inhibitors, and our results call for more frontline targeted therapy trials in gDDRm carriers to prolong the progression time. IMPLICATIONS FOR PRACTICE: Results of this study suggested that positive germline DNA damage repair gene mutation (gDDRm) status predicted earlier progression to castration resistance in patients with de novo metastatic and castration-sensitive prostate cancer (mCSPC). These findings indicated the importance of intense therapy for some subgroups of mCSPC, especially for mCSPC harboring gDDRm with low-volume disease. Moreover, gDDRm was a good therapeutic target for poly (ADP-ribose) polymerase inhibitors, and these findings call for more molecular marker driven trials moving to the mTNPC setting.

A nomogram for predicting survival in patients with de novo metastatic breast cancer: a population-based study.

BACKGROUND: 5-10% of patients are diagnosed with metastatic breast cancer (MBC) at the initial diagnosis. This study aimed to develop a nomogram to predict the overall survival (OS) of these patients. METHODS: de novo MBC patients diagnosed in 2010-2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. They were randomly divided into a training and a validation cohort with a ratio of 2:1. The best subsets of covariates were identified to develop a nomogram predicting OS based on the smallest Akaike Information Criterion (AIC) value in the multivariate Cox models. The discrimination and calibration of the nomogram were evaluated using the Concordance index, the area under the time-dependent receiver operating characteristic curve (AUC) and calibration curves. RESULTS: In this study, we included 7986 patients with de novo MBC. The median follow-up time was 36 months (range: 0-83 months). Five thousand three-hundred twenty four patients were allocated into the training cohort while 2662 were allocated into the validation cohort. In the training cohort, age at diagnosis, race, marital status, differentiation grade, subtype, T stage, bone metastasis, brain metastasis, liver metastasis, lung metastasis, surgery and chemotherapy were selected to create the nomogram estimating the 1-, 3- and 5- year OS based on the smallest AIC value in the multivariate Cox models. The nomogram achieved a Concordance index of 0.723 (95% CI, 0.713-0.733) in the training cohort and 0.719 (95% CI, 0.705-0.734) in the validation cohort. AUC values of the nomogram indicated good specificity and sensitivity in the training and validation cohort. Calibration curves showed a favorable consistency between the predicted and actual survival probabilities. CONCLUSION: The developed nomogram reliably predicted OS in patients with de novo MBC and presented a favorable discrimination ability. While further validation is needed, this may be a useful tool in clinical practice.

Does ductal adenocarcinoma of the prostate (DA) have any prognostic impact on patients with de novo metastatic prostate cancer?

BACKGROUND: The prognostic value of ductal adenocarcinoma of the prostate (DA) in nonmetastatic prostate cancer (PCa) has been identified in many studies. However, it remains unknown whether DA is an adverse prognostic factor in metastatic PCa (mPCa). METHOD: Data from 634 mPCa patients histopathologically documented with DA or/and acinar adenocarcinoma of the prostate in our center between 2012 and 2018 were retrospectively analyzed. Propensity score matching (PSM) was used to balance the baseline features. Data from the Surveillance, Epidemiology, and End Results (SEER) database were utilized to validate our findings. Castration-resistant PCa-free survival (CFS), overall survival (OS), and cancer-specific survival (CSS) were set as endpoints. RESULTS: DA was confirmed in 35 of 634 (5.5%) patients. Among the DA-positive patients, 7 of 35 (20%) and 28 of 35 (80%) harbored high (DA ≥ 50%) and low (DA < 50%) DA components, respectively. DA was not associated with poorer median CFS (mCFS) or median OS (mOS) either before PSM (mCFS: 16.9 vs 18.4 month, P = .814; mOS: 42.0 vs 70.1 month, P = .796) or after PSM (mCFS: 16.9 vs 16.9 month, P = .949; mOS: 42.0 vs 79.9 month, P = .960). Likewise, in the SEER data, DA-positive patients (n = 15 153) shared similar median CSS (25.0 vs 28.0 month, P = .206) and OS (26.0 vs 35.0 month, P = .095) with DA-negative patients (n = 70). No prognostic difference was found between patients with high and low DA components. CONCLUSION: We conducted the first study investigating the prognostic value of DA in de novo mPCa. DA was not associated with adverse clinical outcomes in mPCa patients. These findings are helpful for prognostic evaluation, treatment decision making and counseling in mPCa patients.

Factors associated with improved outcomes for metastatic inflammatory breast cancer patients.

PURPOSE: Controversy exists regarding the role of locoregional therapy for stage IV inflammatory breast cancer (IBC). This study aims to determine indicators of prognosis, including primary tumor resection, for stage IV IBC patients. METHODS: Using the National Cancer Data Base, female patients diagnosed 2010-2013 with unilateral a priori metastatic T4d invasive adenocarcinoma of the breast were identified. We conducted propensity score matched analysis to balance confounders of surgery versus no-surgery. Stratified log-rank test and double-robust estimation under the Cox model were used to assess the effect of surgery, and margins, on overall survival (OS) in the propensity score matched cohort. RESULTS: Of 1266 patients, 41% underwent surgery. In the unmatched cohort, median OS of the surgery and no-surgery groups was 36 and 20 months, respectively (p < 0.001). In the matched cohort (n = 588), the median OS of surgery and no-surgery groups was 29 and 27 months, respectively (p = 0.052). Patients with negative margin surgery (p = 0.024), hormone receptor-positive (p = 0.019), HER2-positive disease (p < 0.0001), treated with chemotherapy (p < 0.0001) and hormonal therapy (p < 0.0001), had better survival. Those with brain metastases had increased risk of death (p < 0.0001). CONCLUSION: This study represents the largest cohort of metastatic IBC patients, and identified negative margin surgery, systemic therapy, hormone receptor and HER2-positive disease as factors associated with improved outcomes. While these findings should be interpreted cautiously, they may be used to guide further investigations into local control and quality of life in this patient population with limited treatment options.

Survival with metastatic breast cancer based on initial presentation, de novo versus relapsed.

PURPOSE: We hypothesized different Overall Survival (OS) in metastatic breast cancer (MBC) after relapse vs de novo presentation. METHODS: We identified women in British Columbia with MBC diagnosed between 01/2001 and 12/2009. OS from MBC was calculated for relapsed vs de novo cohorts in 3 subgroups, based on hormone receptors (HR) and HER2 status. Age at MBC, disease-free interval (DFI), de novo vs relapsed, year of MBC diagnosis, and systemic treatment were entered into univariable and multivariable analyses. RESULTS: We identified 3645 pts with known HR of which 2796 had known HER2. Median follow-up was 91 months. Median OS was longer for de novo vs relapsed MBC: HR+/HER2- 34 versus 23 months (mos) (p < 0.0001), HR-/HER2- (TN) 11 versus 8 mos (p = 0.02), HER2+ 29 versus 15 mos (p < 0.0001). For TN disease, no variable independently discriminated a group with increased risk of death. For both the HR +/HER2- and the HER2 + groups, relapsed vs de novo status (HzR 1.4 [95% CI 1.2-1.5; p < 0.0001], and HzR 1.6 [95% CI 1.4-1.9; p < 0.0001], respectively) and age >50 (HzR 1.2 [95% CI 1.1-1.4; p = 0.001] and HzR 1.3 [95% CI 1.1-1.5; p = 0.01], respectively) were associated with increased risk of death on multivariable analysis. CONCLUSION: These data provide information that may guide discussions about prognosis between physicians and patients with MBC. In addition, it highlights the importance of stratifying for initial stage at diagnosis in future MBC therapeutic trials.

Occurrence and outcome of de novo metastatic breast cancer by subtype in a large, diverse population.

PURPOSE: To examine the occurrence and outcomes of de novo metastatic (Stage IV) breast cancer, particularly with respect to tumor HER2 expression. METHODS: We studied all 6,268 de novo metastatic breast cancer cases diagnosed from 1 January 2005 to 31 December 2011 and reported to the California Cancer Registry. Molecular subtypes were classified according to HER2 and hormone receptor (HR, including estrogen and/or progesterone receptor) expression. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) of Stage IV versus Stage I-III breast cancer; Cox proportional hazards regression was used to assess relative hazard (RH) of mortality. RESULTS: Five percent of invasive breast cancer was metastatic at diagnosis. Compared to patients with earlier stage disease, patients with de novo metastatic disease were significantly more likely to have HER2+ tumors (HR+/HER2+: OR 1.29, 95 % CI 1.17-1.42; HR-/HER2+: OR 1.40, 95 %CI 1.25-1.57, vs. HR+/HER2-). Median survival improved over time, but varied substantially across race/ethnicity (Asians: 34 months; African Americans: 6 months), neighborhood socioeconomic status (SES) (highest: 34 months, lowest: 20 months), and molecular subtype (HR+/HER2+: 45 months; triple negative: 12 months). In a multivariable model, triple negative (RH 2.85, 95 % CI 2.50-3.24) and HR-/HER2+ (RH 1.60, 95 % CI 1.37-1.87) had worse, while HR+/HER2+ had similar, risk of all-cause death compared to HR+/HER2- breast cancer. CONCLUSIONS: De novo metastatic breast cancer was more likely to be HER2+. Among metastatic tumors, those that were HER2+ had better survival than other subtypes.

Should docetaxel be standard of care for patients with metastatic hormone-sensitive prostate cancer? Pro and contra.

Following the results of the TAX-327 study, questions have been raised as to whether administering chemotherapy to men with prostate cancer before symptomatic disease progression when receiving standard hormonal treatment can improve the duration and quality of patient survival. The GETUG-AFU-15 and CHAARTED studies both assessed the efficacy and tolerability of androgen deprivation therapy (ADT) with or without docetaxel in men with metastatic hormone-naive prostate cancer. Both studies included a mix of patients with de novo metastatic disease (∼75%) and patients who developed metastases following treatment of localized disease. A short course of ADT was allowed in both trials prior to accrual. Key differences between the two studies include the number of patients with high-volume metastases (GETUG-AFU-15: 52%; CHAARTED: 65%) and number of docetaxel cycles (GETUG-AFU-15: up to nine cycles; CHAARTED six cycles). Both studies reported an improvement in progression-free survival with docetaxel plus ADT versus ADT alone. The GETUG-AFU-15 did not find a significant difference in the primary end point of overall survival (OS) {hazard ratio (HR) 0.9 [95% confidence interval (CI) 0.7-1.2]; P = 0.44} for ADT plus docetaxel versus ADT alone. The CHAARTED study met the primary end point of OS [HR 0.61 (95% CI 0.47-0.80); P = 0.0003], and in a subset analysis reported the greatest improvement in OS for patients with high-volume disease [HR 0.60 (95% CI 0.45-0.81); P = 0.0006]. The following article debates the results from the GETUG-AFU-15 and CHAARTED studies and asks whether medical practice should be changed for patients with metastatic hormone-naive prostate cancer based on the results of one positive study.

Survival of patients with de-novo metastatic breast cancer: analysis of data from a large breast cancer-specific private practice, a university-based cancer center and review of the literature.

Approximately 6 % of patients with breast cancer are diagnosed with de-novo distant metastases. We set out to look at two cohorts of patients seen at breast cancer-specific practices, compare the results to other reports and larger databases, and see how advances in treatment have impacted overall survival (OS). The records from a large breast cancer oncology private practice and a second data set from the University of Miami/Sylvester Comprehensive Cancer Center (UM/SCCC) tumor database were, retrospectively, reviewed to identify patients with de-novo metastases. We included those patients identified to have metastatic disease within 3 months of diagnosis of a breast primary cancer. Patients diagnosed between 1996 and 2006 were chosen for our study population. The OS for the private practice was 41.0 months (46.0 for ER positive and 26.0 for ER negative) and 36.0 months for UM/SCCC (52 months for ER positive and 36 months for ER negative). ER negativity and CNS- or visceral-dominant disease were associated with a significantly worse prognosis within the private practice. Dominant site was associated with a significantly worse prognosis within the UM/SCCC database but with a trend also for ER negativity. Age and ethnicity did not contribute significantly to the survival of patients within either cohort. The median survival in both cohorts and most other reported series was larger than that seen in the surveillance, epidemiology, and end results program and the National Cancer Database. The median OS among patients with de-novo metastatic breast cancer treated within two breast-specific oncology practices was over 3 years, which appears better than larger, more inclusive databases and publications from earlier decades.

Real-world progression in the survival of de novo Metastatic prostate cancer over the past decade.

BACKGROUND: The impact of evolving treatment strategies for metastatic prostate cancer (mPCa) on real-world survival is not well understood. We analyzed changes in mPCa survival over the past decade and discussed the potential driving factors behind these changes. METHODS: Our study involved 43,228 mPCa patients (2004-2020) from the SEER database, divided into 4 diagnostic periods. We used a multivariate Cox proportional hazards model to evaluate diagnostic periods' influence on overall mortality (OM) and prostate cancer-specific mortality (PSM), and calculated relative median survival improvements between adjacent periods. Subgroup analyses based on age and distant metastasis sites were conducted. RESULTS: Patients diagnosed in 2016 to 2020 experienced significantly reduced mortality risk compared to those in 2004 to 2007 (HR 0.64 for OM, HR 0.62 for CSM, both P < 0.001). The study period witnessed an absolute improvement in median overall survival (OS) and prostate cancer-specific survival (PCSS), 17 months (54.8%) and 25 months (67.6%) respectively. The most rapid relative survival improvement occurred post-2016, with a 29.7% increase in median OS and a 37.8% increase in PCSS compared to 2012 to 2015. There was a significant reduction in mortality risk throughout the study period in both age groups (age <75 and ≥75), but absolute survival gains were smaller in the older group (24 months [68.6%] vs. 8 months [32%] for OS, 36 months [90.0%] vs. 11 months [33.3%] for PCSS), with lower relative survival improvements after 2016 (37.2% vs. 17.9% for OS, 49% vs. 22.2% for PCSS). All metastasis site subgroups (except M1a) exhibited a significant reduction in mortality risk (all P < 0.001). Absolute survival improvements were 58 months (134.9%) for M1a, 16 months (50.0%) for M1b, and 17 months (54.8%) for M1c. CONCLUSION: The survival of mPCa have significantly improved over the past decade, although the progress is slower in elderly patients. Investigating the underlying reasons for survival differences among various patient profiles can further refine mPCa treatment strategies.

Breast surgery for patients with de novo metastatic breast cancer: A meta-analysis of randomized controlled trials.

The role of breast surgery in the treatment of patients with de novo metastatic breast cancer(dnMBC) remains controversial, with conflicting trial results. We did a meta-analysis to comprehensively investigate and assess whether breast surgery is associated with survival and quality of life outcomes in patients with dnMBC.We systematically searched PubMed, Embase, Google Scholar, Scopus, and Web of Science, from database inception to March 30, 2022, for randomized controlled trials(RCTs) that compared breast surgery or locoregional therapy with non-surgical treatment based on systemic therapy for managing dnMBC.We also reviewed abstracts and presentations from major conference proceedings. We excluded non-randomised trials and considered only papers published in English. The primary outcomes were overall survival(OS),locoregional progression-free survival(LPFS), distant progression-free survival(DPFS), and quality of life(QoL). The quality of RCTs was appraised with the Cochrane Collaboration risk of bias tool. Random-effects model or fixed effects model were used to calculate the effect sizes of included RCTs.Quality of evidence was assessed with GRADE criteria. Data analysis was performed with STATA 17.0. A total of 1018 women from seven randomized clinical trials were included in the analysis. Pooled analyses revealed that compared with systemic therapy, breast surgery was not associated with beneficial outcomes in OS(hazard ratio [HR],0.87; 95%CI,0.68 to 1.11; I2 = 53.08 %; p = 0.265),DPFS(HR,1.20; 95%CI,0.94 to 1.54; I2 = 86.45 %; p = 0.136), or QoL-global health status (standardized mean difference[SMD],0.08; 95%CI,-0.15 to 0.32; I2 = 79.45 %; p = 0.478) and QoL-mental-physical functionality(SMD,-0.19; 95%CI,-0.50 to 0.13; I2 = 0.00 %; p = 0.255), but was associated with a benefit in LPFS(HR,0.27; 95%CI,0.19 to 0.38; I2 = 84.16 %; p < 0.001). These findings were consistent in subgroup analyses of the timing of surgery, site and number of metastases and tumor molecular subtype. The evidence grade was moderate because of the substantial heterogeneity among studies. Based on the RCTs evidence, we found that breast surgery may benefit locoregional control but does not prolong OS and improve QoL in patients with dnMBC. The Prospero registration number: CRD42020206460.

Attrition in the First Three Therapy Lines in Patients with Advanced Breast Cancer in the German Real-World PRAEGNANT Registry.

Background With more effective therapies for patients with advanced breast cancer (aBC), therapy sequences are becoming increasingly important. However, some patients might drop out of the treatment sequence due to deterioration of their life status. Since little is known about attrition in the real-world setting, this study assessed attrition in the first three therapy lines using a real-world registry. Methods Patients with information available on the first three therapy lines were selected from the German PRAEGNANT registry (NCT02338167). Attrition was determined for each therapy line using competing risk analyses, with the start of the next therapy line or death as endpoints. Additionally, a simple attrition rate was calculated based on the proportion of patients who completed therapy but did not start the next therapy line. Results Competitive risk analyses were performed on 3988 1st line, 2651 2nd line and 1866 3rd line patients. The probabilities of not starting the next therapy line within 5 years after initiation of 1st, 2nd and 3rd line therapy were 30%, 24% and 24% respectively. Patients with HER2-positive disease had the highest risk for attrition, while patients with HRpos/HER2neg disease had the lowest risk. Attrition rates remained similar across molecular subgroups in the different therapy lines. Conclusion Attrition affects a large proportion of patients with aBC, which should be considered when planning novel therapy concepts that specifically address the sequencing of therapies. Taking attrition into account could help understand treatment effects resulting from sequential therapies and might help develop treatment strategies that specifically aim at maintaining quality of life.

De novo metastatic head and neck squamous cell carcinoma: Why does locoregional control "always" matter?

De novo metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) constitutes 10% of recurrent/metastatic (RM) cases. Radiotherapy (RT) has a crucial role in the treatment of locally advanced HNSCC, however its application on RM diseases is still limited. The advent of immune checkpoint inhibitors (ICIs) improves the survival of RM HNSCC, however median overall survival is still limited. Integration of locoregional RT with ICIs in de novo metastatic HNSCC represents a promising treatment option. This perspective aims to explore the role of the combination of locoregional and systemic treatment in improving outcomes for synchronous de novo metastatic HNSCC patients and highlights the principal crucial point in decision making.

Should breast surgery be considered for patients with de novo metastatic inflammatory breast cancer?

INTRODUCTION: We aimed to identify factors predicting surgery for de novo stage IV inflammatory breast cancer (IBC) and determine the association of surgery with overall survival (OS). METHODS: Female patients with unilateral AJCC clinical stage IV IBC treated 2010-2018 in the NCDB were identified. Logistic regression and multivariable proportional Cox hazards regressions determined factors associated with treatment and OS. RESULTS: Of 1049 patients, 29.1% underwent breast surgery (BS) and 70.9% had no surgery (NS). Increasing age and more recent treatment year were significantly associated with NS. 2-Year OS was superior in BS patients (71% vs 38% NS). Single-site and bone-only metastasis had no association with treatment type or OS. CONCLUSION: Contrary to guidelines, 1/3 of de novo stage IV IBC patients underwent BS, and had an independent OS benefit irrespective of extent or site of metastasis. Further research is needed to determine which patients with stage IV IBC should undergo BS.

The metastasis patterns and their prognostic features in patients with de novo metastatic breast cancer of different ages.

PURPOSE: The prognostic outcomes of metastasis patterns in patients with de novo metastatic breast cancer (dnMBC) of different ages are unknown. Our study used a large-scale data to investigate the metastasis patterns and prognostic features in dnMBC of different ages. METHODS: Total 24,698 women with dnMBC in the Surveillance, Epidemiology and End Results database (2010-2018) were divided into three groups by age. Chi-squared test was used to compare metastasis patterns and logistic regression was performed to investigate the risk of age and specific organ metastases. Kaplan-Meier survival curves were used to compare the overall survival. RESULTS: In three groups, young group had the largest proportion of liver metastases (35.2% vs. 28.2% vs. 21.1%, p < 0.001), and elderly group had the largest proportion of lung metastases (22.6% vs. 30.0% vs. 35.0%, p < 0.001) and the lowest proportion of bone metastases (65.7% vs. 67.6% vs. 64.4%, p < 0.001). In young group, patients with liver metastases had better prognosis than patients with lung metastases (MST: 34 months vs. 29 months, p = 0.041), but in middle-aged and elderly groups, the prognosis of lung metastases was better than that of liver metastases (MST in middle-aged group: 24 months vs. 20 months, p = 0.002; MST in elderly group: 12 months vs. 6 months, p < 0.001). CONCLUSION: DnMBC patients at different age have distinct metastasis patterns and prognostic features. The findings lend support to consideration of tailored management and surveillance strategies for different age patients.