Importance The presence of bone pain is significantly associated with worse overall survival (OS) in patients with castration-resistant prostate cancer. However, there are few data regarding bone ...pain and survival outcomes in the context of metastatic, hormone-sensitive prostate cancer (MHSPC). Objective To compare survival outcomes among patients with MHSPC by presence or absence of baseline bone pain at diagnosis. Design, Setting, and Participants This post hoc secondary analysis, conducted from September 1 to December 31, 2023, used patient-level data from SWOG-1216, a phase 3, prospective randomized clinical trial that enrolled patients with newly diagnosed MHSPC from 248 academic and community centers across the US from March 1, 2013, to July 15, 2017. All patients in the intention-to-treat population who had available bone pain status were eligible and included in this secondary analysis. Interventions In the SWOG-1216 trial, patients were randomized (1:1) to receive either androgen deprivation therapy (ADT) with orteronel, 300 mg orally twice daily (experimental group), or ADT with bicalutamide, 50 mg orally daily (control group), until disease progression, unacceptable toxic effects, or patient withdrawal. Main Outcomes and Measures Overall survival was the primary end point; progression-free survival (PFS) and prostate-specific antigen (PSA) response were secondary end points. Cox proportional hazards regression models were used for both univariable and multivariable analyses adjusting for age, treatment type, Gleason score, disease volume, Zubrod performance status, and PSA level. Results Of the 1279 male study participants, 301 (23.5%) had baseline bone pain at MHSPC diagnosis and 896 (70.1%) did not. Bone pain status was unavailable in 82 patients (6.4%). The median age of the 1197 patients eligible and included in this secondary analysis was 67.6 years (IQR, 61.8-73.6 years). Compared with patients who did not experience bone pain, those with baseline bone pain were younger (median age, 66.0 IQR, 60.1-73.4 years vs 68.2 IQR, 62.4-73.7 years; P = .02) and had a higher incidence of high-volume disease (212 70.4% vs 373 41.6%; P < .001). After adjustment, bone pain was associated with shorter PFS and OS. At a median follow-up of 4.0 years (IQR, 2.5-5.4 years), patients with bone pain had median PFS of 1.3 years (95% CI, 1.1-1.7 years) vs 3.7 years (95% CI, 3.3-4.2 years) in patients without initial bone pain (adjusted hazard ratio AHR, 1.46; 95% CI, 1.22-1.74; P < .001) and OS of 3.9 years (95% CI, 3.3-4.8 years) vs not reached (NR) (95% CI, 6.6 years to NR) in patients without initial bone pain (AHR, 1.66; 95% CI, 1.34-2.05; P < .001). Conclusions and Relevance In this post hoc secondary analysis of the SWOG-1216 randomized clinical trial, patients with baseline bone pain at MHSPC diagnosis had worse survival outcomes than those without bone pain. These data suggest prioritizing these patients for enrollment in clinical trials, may aid patient counseling, and indicate that the inclusion of bone pain in prognostic models of MHSPC may be warranted. Trial Registration ClinicalTrials.gov Identifier: NCT01809691
Patients with synchronous (de novo) metastatic castration-sensitive prostate cancer appear to have worse survival outcomes and shorter time to develop castration resistance than patients with ...metachronous disease. However, the impact of synchronous metastasis on outcomes in metastatic castration-resistant prostate cancer (mCRPC) setting is unknown in patients without prior exposure to androgen receptor pathway inhibitors (ARPIs). In this study, we assessed the impact of initial timing of metastasis (synchronous vs metachronous) on survival outcomes of patients with new-onset mCRPC in a real-world population treated with first-line abiraterone or enzalutamide.
Data were collected retrospectively from 323 patients with a confirmed diagnosis of mCRPC who received ARPIs as first-line therapy and had no prior exposure to ARPIs. The study endpoints were progression-free survival and overall survival.
The results showed that median overall survival was significantly shorter in patients with synchronous disease than those with metachronous disease (26 vs 38.7 months, HR 1.42, 95% CI 1.09-1.86,
= .011). However, there was no difference in median progression-free survival.
The initial presentation with synchronous metastasis remained an independent factor associated with shorter OS in the multivariable analysis. These hypothesis-generating data, after external validation, may have implications in patient counseling, prognostication, and design of future clinical trials in the new-onset mCRPC setting.
We compared gene expression between de novo metastatic prostate cancer and metastatic relapse after local therapy. The results reveal upregulation of inflammatory pathways in de novo cases and of ...androgen response pathways in metastatic relapse. These findings suggest a potential for personalized therapy.
It has been reported that patients with de novo metastatic castration-sensitive prostate cancer (dn-mCSPC) have worse prognosis and outcomes than those whose cancer relapses after prior local therapy (PLT-mCSPC). Our aim was to interrogate and validate underlying differences in tumor gene expression profiles between dn-mCSPC and PLT-mCSPC.
The inclusion criteria were histologically confirmed prostate adenocarcinoma and the availability of RNA sequencing data for treatment-naïve primary prostate tissue. RNA sequencing was performed by Tempus or Caris Life Sciences, both of which have Clinical Laboratory Improvement Amendments certification. The Tempus cohort was used for interrogation, while the Caris cohort was used for validation. Differential gene expression analysis between the cohorts was conducted using the DEseq2 pipeline. The resulting gene expression profiles were further analyzed using Gene Set Enrichment software to identify pathways with enrichment in each cohort.
Overall, 128 patients were eligible, of whom 70 were in the Tempus cohort (dn-mCSPC 37, PLT-mCSPC 41) and 50 were in the Caris cohort (dn-mCSPC 30, PLT-mCSPC 20). Tumor tissues from patients with dn-mCSPC had higher expression of genes associated with inflammation pathways, while tissues from patients with PLT-mCSPC had higher expression of genes involved in oxidative phosphorylation, fatty acid metabolism, and androgen response pathways.
Our study revealed upregulation of distinct genomic pathways in dn-mCSPC in comparison to PLT-mCSPC. These hypothesis-generating data could guide personalized therapy for men with prostate cancer and explain different survival outcomes for dn-mCSPC and PLT-mCSPC.
We measured gene expression levels in tumors from patients with metastatic castration-sensitive prostate cancer. In patients with metastatic disease at first diagnosis, inflammatory pathways were upregulated. In patients whose metastasis occurred on relapse after treatment, androgen response pathways were upregulated. These findings could help in personalizing therapy for prostate cancer and explaining differences in survival.
Black patients present with more aggressive disease and experience higher mortality than White patients with prostate cancer. Race and social determinants of health influence prostate cancer-specific ...mortality and overall survival (OS); however, in a previous trial, Black patients did not have inferior outcomes compared with White patients, possibly because of equitable access to care available in a clinical trial setting.
To compare differences in survival outcomes of patients with metastatic castration-sensitive prostate cancer (mCSPC) by race in a phase 3 trial with a large proportion of Black patients.
This secondary analysis of patient-level data of a prospective phase 3 randomized clinical trial included patients with newly diagnosed mCSPC enrolled between March 1, 2013, and July 15, 2017. Analysis was conducted between December 2022 and February 2023.
Patients receiving androgen deprivation therapy were randomized (1:1) to receive either orteronel 300 mg orally twice daily (experimental group) or bicalutamide 50 mg orally daily (control group).
OS, with progression-free survival (PFS) as a secondary end point.
Among 1313 participants, 135 (10%) identified as Black and 1077 (82%) as White, with an equal racial distribution between groups. Black patients were younger (median IQR age, 65.8 60-70 vs 68.4 62.5-74.1 years; P = .001) and had a higher median (IQR) baseline prostate-specific antigen response rate than White patients (54.7 19.8-222.0 vs 26.7 9.2-96.0 ng/mL; P < .001). At a median follow-up of 4.9 years, Black and White patients had similar median PFS (2.3 years; 95% CI, 1.8-1.4 years vs 2.9 years; 95% CI, 2.5-3.3 years; P = .71) and OS (5.5 years; 95% CI, 4.8-NR vs 6.3 years; 95% CI, 5.7-NR; P = .65). The multivariable analysis confirmed similar PFS and OS after adjusting for known prognostic factors. No interaction between race and treatment was observed.
In this secondary analysis of a randomized clinical trial studying androgen deprivation therapy with first- or second-generation androgen receptor pathway inhibitors, both Black and White patients demonstrated similar OS and PFS. Equitable access to care may reduce historical differences in outcomes between Black and White patients with advanced prostate cancer.
ClinicalTrials.gov Identifier: NCT01809691.
A 64-year-old man presented with symptoms indicative of superior vena cava syndrome. Imaging work-up revealed an obstructing right atrial mass, which was subsequently excised and diagnosed as primary ...cardiac lymphoma. Post-surgery, the patient showed significant clinical improvement and was started on a chemotherapy regimen with complete remission at 1 year.
