A real-world comparison of docetaxel versus abiraterone acetate for metastatic hormone-sensitive prostate cancer.

BACKGROUND: Docetaxel (D) or secondary hormonal therapy (SHT) each combined with androgen deprivation therapy (ADT) represent possible treatment options in males with metastasized hormone-sensitive prostate cancer (mHSPC). Real-world data comparing different protocols are lacking yet. Thus, our objective was to compare the efficacy and safety of abiraterone acetate (AA)+ADT versus D+ADT in mHSPC. METHODS: In a retrospective multicenter analysis including males with mHSPC treated with either of the aforementioned protocols, overall survival (OS), progression-free survival 1 (PFS1), and progression-free survival 2 (PFS2) were assessed for both cohorts. Median time to event was tested by Kaplan-Meier method and log-rank test. The Cox-proportional hazards model was used for univariate and multivariate regression analyses. RESULTS: Overall, 196 patients were included. The AA+ADT cohort had a longer PFS1 in the log-rank testing (23 vs. 13 mos., p < 0.001), a longer PFS2 (48 vs. 33 mos., p = 0.006), and longer OS (80 vs. 61 mos., p = 0.040). In the multivariate analyses AA+ADT outperformed D+ADT in terms of PFS1 (HR = 0.34, 95% CI = 0.183-0.623; p = 0.001) and PFS2 (HR = 0.33 95% CI = 0.128-0.827; p = 0.018), respectively, while OS and toxicity rate were similar between both groups. CONCLUSIONS: AA+ADT is mainly associated with a similar efficacy and overall toxicity rate as D+ADT. Further prospective research is required for validation of the clinical value of the observed benefit of AA+ADT for progression-free end-points.

Perceptions of involvement in advance care planning and emotional functioning in patients with advanced cancer.

PURPOSE: Advance Care Planning (ACP) is positively associated with the quality of care, but its impact on emotional functioning is ambiguous. This study investigated the association between perceptions of ACP involvement and emotional functioning in patients with advanced cancer. METHODS: This study analyzed baseline data of 1,001 patients of the eQuiPe study, a prospective, longitudinal, multicenter, observational study on quality of care and quality of life in patients with advanced cancer in the Netherlands. Patients with metastatic solid cancer were asked to participate between November 2017 and January 2020. Patients' perceptions of ACP involvement were measured by three self-administered statements. Emotional functioning was measured by the EORTC-QLQ-C30. A linear multivariable regression analysis was performed while taking gender, age, migrant background, education, marital status, and symptom burden into account. RESULTS: The majority of patients (87%) reported that they were as much involved as they wanted to be in decisions about their future medical treatment and care. Most patients felt that their relatives (81%) and physicians (75%) were familiar with their preferences for future medical treatment and care. A positive association was found between patients' perceptions of ACP involvement and their emotional functioning (b=0.162, p<0.001, 95%CI[0.095;0.229]) while controlling for relevant confounders. CONCLUSIONS: Perceptions of involvement in ACP are positively associated with emotional functioning in patients with advanced cancer. Future studies are needed to further investigate the effect of ACP on emotional functioning. TRIAL REGISTRATION NUMBER: NTR6584 Date of registration: 30 June 2017 IMPLICATIONS FOR CANCER SURVIVORS: Patients' emotional functioning might improve from routine discussions regarding goals of future care. Therefore, integration of ACP into palliative might be promising.

Treatment of Metastasized Prostate Cancer Beyond Progression After Upfront Docetaxel-A Real-world Data Assessment.

BACKGROUND: Besides second-generation hormone therapy (sHT), upfront docetaxel along with androgen deprivation therapy is the current standard of care for metastasized hormone-sensitive prostate cancer (mHSPC). Evidence on second-line therapy upon progression on chemohormonal treatment outside clinical trials is scarce. OBJECTIVE: To comparatively assess the efficacy of subsequent therapy after upfront docetaxel in mHSPC in a real-world setting. DESIGN, SETTING, AND PARTICIPANTS: This is a retrospective multicenter analysis. Males with mHSPC on androgen-deprivation therapy progressed to castration-resistant prostate cancer (CRPC) after upfront docetaxel. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS), progression-free survival 2 (PFS2), and time to progression 2 (TTP2) were assessed. Chi-square test and Mann-Whitney U test were used for univariate comparison between the sHT and non-sHT (other therapies) cohorts. Median time to event was tested by Kaplan-Meier method and log-rank test. Univariate and multivariate analysis regression was performed with the Cox proportional-hazard model. RESULTS AND LIMITATIONS: Sixty-five patients were included in the final analysis. Median TTP2 was 20 mo, median PFS2 was 29 mo, and median OS was not reached; sHT was an independent predictor of favorable PFS2 as compared with non-sHT. Time to CRPC was also confirmed to be the strongest predictor for novel endpoints PFS2 and TTP2. Time to CRPC >18 mo conferred advantage to sHT over non-sHT in relation to PFS2 and OS. Second-line therapies were well tolerated. The analysis is prone to inherent flaws and biases due to its retrospective nature. CONCLUSIONS: In real-world patients progressing after upfront docetaxel, sHT is independently associated with favorable PFS2 favoring drug class switch. Longer time to CRPC predicts strongly for superior PFS2 and TTP2. Further prospective research is warranted in order to guide treatment sequencing and improve outcomes and quality of life of males with metastasized prostate cancer. PATIENT SUMMARY: We analyzed the efficacy of second-line therapy after docetaxel in hormone-dependent metastatic prostate cancer. Novel hormone therapy appears to be a preferable option for deferring progression optimally. Larger patient databases are eagerly awaited.

Paediatric nodal marginal zone B-cell lymphadenopathy of the neck: a Haemophilus influenzae-driven immune disorder?

Many hyperplasias and lymphomas of marginal zone B-cells are associated with infection. We identified six children and one adolescent with cervical lymphadenopathy showing prominent polyclonal nodal marginal zone hyperplasia (pNMZH) and four adolescents with monoclonal paediatric nodal marginal zone lymphoma (pNMZL). The clonality status was assessed using BIOMED-2-IG PCR analysis. Haemophilus influenzae was identified in all six cases of pNMZH that could be tested by direct culture (N = 3) or a very sensitive PCR for the H. influenzae gyrase gene in frozen materials (N = 5). H. influenzae was not detected in three pNMZLs and 28 non-specific reactive cervical lymph nodes of age-matched controls, except for a single control node that was obtained during oropharyngeal surgery for a cleft palate showing very low copy numbers of H. influenzae. pNMZH patients were younger than pNMZL patients (median age 12 versus 21 years). pNMZH showed a prominent nodular appearance with variable fibrosis without acute inflammation. Within the nodules, the expanded germinal centres and variably sized marginal zones were colonized by activated B-cells with weak expression of IgD and lack of CD10 and/or BCL6 expression. Some areas showed skewed light chain expression in plasma cells (4/5 cases lambda). In four cases tested, this was confirmed by flow cytometry for surface Ig (3/4 cases lambda). In contrast, pNMZL showed more extensive expansion of marginal zones by centrocytoid cells and often expression of BCL2 protein. Several H. influenzae strains are known to interact with the constant part of IgD on human B-cells, leading to their polyclonal proliferation and activation. We speculate that in vivo stimulation of IgD+ marginal zone B-cells by this bacterium may be implicated in this particular lymphadenopathy that should be distinguished from monoclonal pNMZL.