Demographic and Clinical Characteristics of Malignant Solitary Fibrous Tumors: A SEER Database Analysis.

BACKGROUND/OBJECTIVES: Solitary fibrous tumors (SFTs) represent a rare mesenchymal malignancy that can occur anywhere in the body. Due to the low prevalence of the disease, there is a lack of contemporary data regarding patient demographics and cancer-control outcomes. METHODS: Within the SEER database (2000-2019), we identified 1134 patients diagnosed with malignant SFTs. The distributions of patient demographics and tumor characteristics were tabulated. Cumulative incidence plots and competing risks analyses were used to estimate cancer-specific mortality (CSM) after adjustment for other-cause mortality. RESULTS: Of 1134 SFT patients, 87% underwent surgical resection. Most of the tumors were in the chest (28%), central nervous system (22%), head and neck (11%), pelvis (11%), extremities (10%), abdomen (10%) and retroperitoneum (6%), in that order. Stage was distributed as follows: localized (42%) vs. locally advanced (35%) vs. metastatic (13%). In multivariable competing risks models, independent predictors of higher CSM were stage (locally advanced HR: 1.6; metastatic HR: 2.9), non-surgical management (HR: 3.6) and tumor size (9-15.9 cm HR: 1.6; ≥16 cm HR: 1.9). CONCLUSIONS: We validated the importance of stage and surgical resection as independent predictors of CSM in malignant SFTs. Moreover, we provide novel observations regarding the independent importance of tumor size, regardless of the site of origin, stage and/or surgical resection status.

Molecular Correlates of Prostate Cancer Visibility on Multiparametric Magnetic Resonance Imaging: A Systematic Review.

BACKGROUND AND OBJECTIVE: Although prostate magnetic resonance imaging (MRI) is increasingly used to diagnose and stage prostate cancer (PCa), the biologic and clinical significance of MRI visibility of the disease is unclear. Our aim was to examine the existing knowledge regarding the molecular correlates of MRI visibility of PCa. METHODS: The PubMed, Scopus, and Web of Science databases were queried through November 2023. We defined MRI-visible and MRI-invisible lesions based on the Prostate Imaging Reporting and Data System (PI-RADS) score, and compared these based on the genomic, transcriptomic, and proteomic characteristics. KEY FINDINGS AND LIMITATIONS: From 2015 individual records, 25 were selected for qualitative data synthesis. Current evidence supports the polygenic nature of MRI visibility, primarily influenced by genes related to stroma, adhesion, and cellular organization. Several gene signatures related to MRI visibility were associated with oncologic outcomes, which support that tumors appearing as PI-RADS 4-5 lesions harbor lethal disease. Accordingly, MRI-invisible tumors detected by systematic biopsies were, generally, less aggressive and had a more favorable prognosis; however, some MRI-invisible tumors harbored molecular features of biologically aggressive PCa. Among the commercially available prognostic gene panels, only Decipher was strongly associated with MRI visibility. CONCLUSIONS AND CLINICAL IMPLICATIONS: High PI-RADS score is associated with biologically and clinically aggressive PCa molecular phenotypes, and could potentially be used as a biomarker. However, MRI-invisible lesions can harbor adverse features, advocating the continued use of systemic biopsies. Further research to refine the integration of imaging data to prognostic assessment is warranted. PATIENT SUMMARY: Magnetic resonance imaging visibility of prostate cancer is a polygenic trait. Higher Prostate Imaging Reporting and Data System scores are associated with features of biologically and clinically aggressive cancer.

Machine learning and explainable artificial intelligence to predict pathologic stage in men with localized prostate cancer.

BACKGROUND: Though several nomograms exist, machine learning (ML) approaches might improve prediction of pathologic stage in patients with prostate cancer. To develop ML models to predict pathologic stage that outperform existing nomograms that use readily available clinicopathologic variables. METHODS: Patients with prostate adenocarcinoma who underwent surgery were identified in the National Cancer Database. Seven ML models were trained to predict organ-confined (OC) disease, extracapsular extension, seminal vesicle invasion (SVI), and lymph node involvement (LNI). Model performance was measured using area under the curve (AUC) on a holdout testing data set. Clinical utility was evaluated using decision curve analysis (DCA). Performance metrics were confirmed on an external validation data set. RESULTS: The ML-based extreme gradient boosted trees model achieved the best performance with an AUC of 0.744, 0.749, 0.816, 0.811 for the OC, ECE, SVI, and LNI models, respectively. The MSK nomograms achieved an AUC of 0.708, 0.742, 0.806, 0.802 for the OC, ECE, SVI, and LNI models, respectively. These models also performed the best on DCA. Findings were consistent on both a holdout internal validation data set as well as an external validation data set. CONCLUSIONS: Our ML models better predicted pathologic stage relative to existing nomograms at predicting pathologic stage. Accurate prediction of pathologic stage can help oncologists and patients determine optimal definitive treatment options for patients with prostate cancer.

The Effect of Surgical Resection on Cancer-Specific Mortality in Pelvic Soft Tissue Sarcoma According to Histologic Subtype and Stage.

Background/Objectives: The impact of surgical resection versus non-resection on cancer-specific mortality (CSM) in soft tissue pelvic sarcoma remains largely unclear, particularly when considering histologic subtypes such as liposarcoma, leiomyosarcoma, and sarcoma NOS. The objective of the present study was to first report data regarding the association between surgical resection status and CSM in soft tissue pelvic sarcoma. Methods: Using data from the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2019, we identified 2491 patients diagnosed with pelvic soft tissue sarcoma. Cumulative incidence plots were used to illustrate CSM and other-cause mortality rates based on the histologic subtype and surgical resection status. Competing risk regression models were employed to assess whether surgical resection was an independent predictor of CSM in both non-metastatic and metastatic patients. Results: Among the 2491 patients with soft tissue pelvic sarcoma, liposarcoma was the most common subtype (41%), followed by leiomyosarcoma (39%) and sarcoma NOS (20%). Surgical resection rates were 92% for liposarcoma, 91% for leiomyosarcoma, and 58% for sarcoma NOS in non-metastatic patients, while for metastatic patients, the rates were 55%, 49%, and 23%, respectively. In non-metastatic patients who underwent surgical resection, five-year CSM rates by histologic subtype were 10% for liposarcoma, 32% for leiomyosarcoma, and 27% for sarcoma NOS. The multivariable competing risk regression analysis showed that surgical resection provided a protective effect across all histologic subtypes in non-metastatic patients (liposarcoma HR: 0.2, leiomyosarcoma HR: 0.5, sarcoma NOS HR: 0.4). In metastatic patients, surgical resection had a protective effect for those with leiomyosarcoma (HR: 0.6) but not for those with sarcoma NOS. An analysis for metastatic liposarcoma was not possible due to insufficient data. Conclusions: In non-metastatic soft tissue pelvic sarcoma, surgical resection may be linked to a reduction in CSM. However, in metastatic patients, this protective effect appears to be limited primarily to those with leiomyosarcoma.

Risk of Biochemical Recurrence and Metastasis in Prostate Cancer Patients Treated with Radical Prostatectomy After a 10-year Disease-free Interval.

BACKGROUND AND OBJECTIVE: Prostate-specific antigen (PSA) testing is used to follow up prostate cancer (PCa) patients treated with radical prostatectomy (RP). Research on PSA thresholds for identifying PCa patients with biochemical recurrence (BCR) who are at a higher risk of progression yielded inconclusive results. This study aims to investigate the risk of late BCR in PCa patients treated with RP and long postoperative (120 mo) undetectable PSA follow-up, and to identify prognostic factors for late BCR within this patient cohort. METHODS: PCa patients treated with curative RP (1992-2012) and free of BCR during the first 120 mo following RP were retrospectively identified within five European tertiary centers; BCR was defined as two consecutive PSA values of ≥0.2 ng/ml. Kaplan-Meier and Cox regression models tested for an association between BCR and patient or tumor characteristics. KEY FINDINGS AND LIMITATIONS: The study cohort consisted of 4639 patients, of whom 243 (5.2%) developed BCR at a medium follow-up of 147 mo. Of those with BCR, 23 (9.5%) subsequently developed metastatic progression. In Kaplan-Meier models, BCR-free survival differed according to advanced tumor status. In multivariable Cox regression models, pT stage (pT3a: hazard ratio [HR]: 1.46; pT3b: HR: 2.42), pathological Gleason score (pGS 3 + 4: HR: 1.71; pGS ≥4 + 3: HR: 2.47), surgical margin (R1/Rx: HR: 1.72), and pNx stage (pNx: HR: 0.72) represented independent predictors for BCR (all p < 0.05). Conversely, age, PSA at diagnosis, and year of surgery failed to achieve independent predictor status for BCR. CONCLUSIONS AND CLINICAL IMPLICATIONS: Among PCa patients with an uneventful follow-up of at least 10 yr after RP, still one in 20 patients subsequently develop late BCR. Nevertheless, late BCR and subsequent progression to metastasis (0.3%) rates in patients with pT2 stage and pGS ≤3 + 4 were strikingly low, implicating that abandoning follow-up beyond an uneventful period of 10 yr is justifiable within this cohort of patients. PATIENT SUMMARY: In this study, prostate cancer patients treated with a radical prostatectomy and at least 10 yr of uneventful prostate-specific antigen testing were identified within five European centers. Relying on these patients, the rate of subsequent late biochemical recurrence was calculated and risk factors were identified for biochemical recurrence following 10 yr of uneventful prostate-specific antigen testing.

Natural history of PIRADS-2 lesions on serial multiparametric magnetic resonance imaging: Real-life data from an Academic Center.

INTRODUCTION/BACKGROUND: The natural history of prostate imaging reporting and data system (PIRADS) score 2 lesions on serial mpMRIs is largely unknown. Herein, we aimed to evaluate the patients with PIRADS-2 index lesions by using serial mpMRI scans to reveal the rates of mpMRI upgrade in PIRADS score and prostate cancer (PCa) detection. METHODS/MATERIALS: All mpMRI scans with a PIRADS-2 index lesion from our mpMRI database were evaluated retrospectively. Data from 214 biopsy-naïve patients with a PIRADS-2 index lesion on the initial mpMRI who then underwent at least 1 follow-up mpMRI were reevaluated by an experienced uroradiologist and only those (n = 172) who had a PIRADS-2 index lesion on the initial mpMRI according to PIRADS v2.1 were included in the study. mpMRI progression was defined as the detection of any PIRADS ≥3 lesion at follow-up mpMRI. Histopathological results were evaluated in patients undergoing biopsy upon mpMRI progression. RESULTS: A total of 172 patients with a mean age of 60.1 ± 8.6 years were evaluated. The median PSA at baseline mpMRI was 4.7 (IQR; 3.3-6.7) ng/dl. Overall mpMRI progression was detected in 54 patients (31.4%), 37 were upgraded to PIRADS-3, 16 to PIRADS-4, and one to PIRADS-5. Multivariate logistic regression analysis revealed that a PSA increase of ≥25% during follow-up was the only predictor of mpMRI upgrade (P = 0.019, OR: 2.384). 30 out of 54 patients underwent a prostate biopsy and PCa was detected in 15 patients; 5 with ISUP grade 1, 10 with ISUP grade 2. CONCLUSIONS: Almost half of the patients with a PIRADS-2 index lesion were upgraded to PIRADS ≥3 when evaluated with serial mpMRI when a PSA increase of ≥25% was observed during follow-up. PCa was detected in half of the patients who underwent a biopsy. Serial mpMRI can be recommended when monitoring patients with elevating PSA ≥25%, a prostate biopsy can be considered upon a mpMRI progression.

Salvage therapies for biochemical recurrence after definitive local treatment: a systematic review, meta-analysis, and network meta-analysis.

PURPOSE: Recent advancements in the management of biochemical recurrence (BCR) following local treatment for prostate cancer (PCa), including the use of androgen receptor signaling inhibitors (ARSIs), have broadened the spectrum of therapeutic options. We aimed to compare salvage therapies in patients with BCR after definitive local treatment for clinically non-metastatic PCa with curative intent. METHODS: In October 2023, we queried PubMed, Scopus, and Web of Science databases to identify randomized controlled trials (RCTs) and prospective studies reporting data on the efficacy of salvage therapies in PCa patients with BCR after radical prostatectomy (RP) or radiation therapy (RT). The primary endpoint was metastatic-free survival (MFS), and secondary endpoints included progression-free survival (PFS) and overall survival (OS). RESULTS: We included 19 studies (n = 9117); six trials analyzed RT-based strategies following RP, ten trials analyzed hormone-based strategies following RP ± RT or RT alone, and three trials analyzed other agents. In a pairwise meta-analysis, adding hormone therapy to salvage RT significantly improved MFS (HR: 0.69, 95% CI: 0.57-0.84, p < 0.001) compared to RT alone. Based on treatment ranking analysis, among RT-based strategies, the addition of elective nodal RT and androgen deprivation therapy (ADT) was found to be the most effective in terms of MFS. On the other hand, among hormone-based strategies, enzalutamide + ADT showed the greatest benefit for both MFS and OS. CONCLUSIONS: The combination of prostate bed RT, elective pelvic irradiation, and ADT is the preferred treatment for eligible patients with post-RP BCR based on our analysis. In remaining patients, or in case of post-RT recurrence, especially for those with high-risk BCR, the combination of ADT and ARSI should be considered.

Prostate Cancer Therapy Cardiotoxicity Map (PROXMAP) for Advanced Disease States: A Systematic Review and Network Meta-analysis with Bayesian Modeling of Treatment Histories.

BACKGROUND AND OBJECTIVE: Recommendations of first-line therapies for metastatic hormone-sensitive (mHSPC), nonmetastatic castrate-resistant (M0CRPC), and metastatic castrate-resistant (mCRPC) prostate cancer do not account for cardiotoxicity due to a lack of clear prior evidence. This manuscript assesses cardiotoxicity of these therapies. METHODS: We searched Ovid Medline, Elsevier Embase, and the Cochrane Library for randomized clinical trials (RCTs) from database inception to January 14, 2024. Network meta-analyses of first-line mHSPC, M0CRPC, and mCRPC therapies were constructed for the five cardiotoxicity metrics defined by the International Cardio-Oncology Society: heart failure, myocarditis, vascular toxicity, hypertension, and arrhythmias. Additional Bayesian network meta-analyses also accounted for prior treatment history. KEY FINDINGS AND LIMITATIONS: Thirteen RCTs (16 292 patients) were included. For mHSPC, androgen deprivation therapy (ADT) plus docetaxel (DTX) plus abiraterone acetate (AA) with prednisone (P) demonstrated a significant increase in hypertension and arrhythmias versus ADT + DTX (risk ratio [RR] 2.85, 95% confidence interval [CI] 1.67-4.89, and RR 2.01, 95% CI 1.17-3.44, respectively); however, no corresponding differences were observed between ADT + DTX plus darolutamide (DAR) and ADT + DTX (RR 1.55, 95% CI 0.73-3.30, and RR 0.94, 95% CI 0.63-1.40, respectively). For mCRPC assuming a history of mHSPC treatment, ADT + AA + P plus olaparib (OLA) demonstrated a statistically significant decrease in hypertension versus ADT + AA + P (RR 0.20, 95% CI 0.16-0.26). M0CRPC results were unremarkable. CONCLUSIONS AND CLINICAL IMPLICATIONS: For mHSPC, ADT + DTX + DAR demonstrates less cardiotoxicity than ADT + DTX + AA + P due to a lower risk of hypertension and arrhythmias from decreased mineralocorticoid excess. In addition, OLA counterintuitively offers decreased hypertension when superimposed on ADT + AA + P for mCRPC treatment after prior androgen deprivation from mHSPC therapy.

Prostate-specific Antigen Nadir and Cancer-Control Outcomes in Real-world Apalutamide-treated Metastatic Hormone-Sensitive Prostate Cancer Patients: A Single-Center Analysis.

BACKGROUND AND OBJECTIVE: Currently available post hoc phase 3 trial-derived data suggest better cancer-control outcomes in apalutamide-treated metastatic hormone-sensitive prostate cancer (mHSPC) patients achieving an (ultra)low prostate-specific antigen (PSA) nadir. This study aims to validate ultralow PSA nadir cutoffs. METHODS: Relying on an institutional prostate cancer database, 107 eligible patients were yielded. The currently available PSA nadir cutoffs (SWOG trial: <0.2 ng/ml; ultralow TITAN trial: ≤0.02 vs 0.02-0.2 vs >0.2 ng/ml) and PSA responses (≥99%) were tested for time to castration-resistant prostate cancer (ttCRPC) and overall survival (OS) in mHSPC patients treated with apalutamide. Finally, comparisons were made against abiraterone mHSPC treatment. KEY FINDINGS AND LIMITATIONS: Overall, 107 mHSPC patients treated with apalutamide at a median age of 68 yr and baseline PSA of 29 ng/ml were included. The highest proportion of included patients (40.2%) achieved an ultralow PSA nadir of ≤0.02 ng/ml. Patients reaching the SWOG 9346-defined PSA nadir of <0.2 ng/ml and ultralow PSA nadir of ≤0.02 ng/ml harbored the longest time to metastatic castration-resistant prostate cancer (mCRPC) and OS (all p < 0.05). Moreover, 80% of mHSPC patients treated with apalutamide achieved a PSA response of ≥99%. These patients also harbored better time to mCRPC and OS outcomes, relative to patients with a <99% PSA response (both p < 0.05). In the second step of analyses, a comparison against abiraterone patients showed a significantly higher rate of achieving an ultralow PSA nadir of ≤0.02 ng/ml: 40.2% versus 8.8% for apalutamide versus abiraterone, resulting in a significantly longer ttCRPC for the apalutamide-treated (37 mo) than for the abiraterone-treated (22 mo) group (p = 0.001), even after multivariable adjustment and in sensitivity analyses for high-risk mHSPC patients only. The study is limited by its retrospective design. CONCLUSIONS AND CLINICAL IMPLICATIONS: In the real-world setting, most mHSPC patients treated with apalutamide achieve an ultralow PSA nadir, which is associated with better cancer-control outcomes. Moreover, a PSA response of ≥99% predicts better outcomes. In head-to-head comparisons, apalutamide achieves better PSA kinetics and ttCRPC outcomes than abiraterone. PATIENT SUMMARY: A prostate-specific antigen (PSA) nadir of <0.02 ng/ml and PSA responses ≥99% are associated with better cancer-control outcomes in metastatic hormone-sensitive prostate cancer patients treated with apalutamide.

Influence of Tumor Characteristics and Time to Metastatic Disease on Oncological Outcomes in Metachronous Metastatic Prostate Cancer Patients.

INTRODUCTION: Metachronous metastatic prostate cancer (mmPCa) patients harbor different characteristics and outcomes, relative to DeNovo metastatic PCa patients. Onset of metastatic disease might be influenced by primary PCa characteristics such as Gleason score (GS) or cancer stage, as well as overall survival (OS) by timing of metastatic onset. PATIENTS AND METHODS: We relied on an institutional tertiary-care database to identify mmPCa patients. Kaplan Meier and Cox Regression models tested for onset of metastases and OS, stratified according to GS, pathological stage and time to mmPCa. RESULTS: Of 341 mmPCa patients, 8% harbored GS6 versus 41% versus 51% GS7 and GS8-10. Median time to onset of metastatic disease was 79 versus 54 versus 41 months for GS6 versus GS7 versus GS8-10 (P = .01). Moreover, median time to onset of metastases was 64 versus 44 months for pT1-2 versus pT3-4 mmPCa patients undergoing radical prostatectomy (P = .027). In multivariable Cox regression models, higher GS and pT-stage was associated with earlier onset of metastases. Additionally, significant OS differences could be observed for time interval of < 24 versus 24-60 versus 60-120 versus ≥ 120 months between primary PCa diagnosis and onset of mmPCa. Specifically, median OS was 56 versus 69 versus 97 months versus not reached (P < .01) for these categories. In multivariable Cox regression, shorter time to metastatic onset was associated with shorter OS. CONCLUSION: Timing of mmPCa is strongly influenced by grading and pT-stage in real-life setting. OS benefits can be observed with longer time interval between primary PCa diagnosis and onset of mmPCa.

Regional Differences in Stage III Nonseminoma Germ Cell Tumor Patients Across SEER Registries.

PURPOSE: We investigated regional differences in patients with stage III nonseminoma germ cell tumor (NSGCT). Specifically, we investigated differences in baseline patient, tumor characteristics and treatment characteristics, as well as cancer-specific mortality (CSM) across different regions of the United States. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database (2004-2018), patient (age, race/ethnicity), tumor (International Germ Cell Cancer Collaborative Group [IGCCCG] prognostic groups) and treatment (systemic therapy and retroperitoneal lymph dissection [RPLND] status) characteristics were tabulated for stage III NSGCT patients, according to 12 SEER registries representing different geographic regions. Multinomial regression models and multivariable Cox regression models testing for cancer-specific mortality (CSM) were used. RESULTS: In 3,174 stage III NSGCT patients, registry-specific patient counts ranged from 51 (1.5%) to 1630 (51.3%). Differences across registries existed for age (12%-31% for age 40+), race/ethnicity (5%-73% for others than non-Hispanic whites), IGCCCG prognostic groups (24%-43% vs. 14-24% vs. 3%-20%, in respectively poor vs. intermediate vs. good prognosis), systemic therapy (87%-96%) and RPLND status (12%-35%). After adjustment, clinically meaningful inter-registry differences remained for systemic therapy (84%-97%) and RPLND (11%-32%). Unadjusted 5-year CSM rates ranged from 7.1% to 23.3%. Finally in multivariable analyses addressing CSM, 2 registries exhibited more favorable outcomes than SEER registry of reference (SEER Registry 12): SEER Registry 4 (Hazard Ratio (HR): 0.36) and SEER Registry 9 (HR: 0.64; both P = .004). CONCLUSION: We identified important regional differences in patient, tumor and treatment characteristics, as well as CSM which may be indicative of regional differences in quality of care or expertise in stage III NGSCT management.

External Validation of Stockholm3 in a Retrospective German Clinical Cohort.

BACKGROUND AND OBJECTIVE: Stockholm3 is a comprehensive blood test amalgamating protein biomarkers, genetic indicators, and clinical data to predict clinically significant prostate cancer risk (International Society of Urological Pathology grade ≥2 upon biopsy). Our study aims to externally validate Stockholm3 and compare its performance with the use of prostate-specific antigen (PSA) and the Rotterdam Prostate Cancer Risk Calculator (RPCRC) for clinically significant prostate cancer detection. METHODS: We gathered data from men subjected to prostate biopsies at the Martini-Klinik, Germany, between 2014 and 2017. Participants were selected based on elevated PSA levels or suspicious digital rectal examinations, all undergoing a 10-12-core systematic biopsy without a magnetic resonance imaging-targeted biopsy. We assessed Stockholm3 and RPCRC performance for clinically significant prostate cancer detection. Furthermore, we compared the proportion of men recommended for biopsy and biopsy outcomes with Stockholm3 and RPCRC against PSA ≥3 ng/ml. KEY FINDINGS AND LIMITATIONS: Our study encompassed 405 biopsied men, with a median age of 66 yr (interquartile range [IQR]: 60-72), PSA levels at 7 ng/ml (IQR: 5.2-10.8), and Stockholm3 scores at 18 (IQR: 10-34). Among them, 128 men (31%) received clinically significant prostate cancer diagnoses. Employing the recommended Stockholm3 threshold (≥15) could have reduced unnecessary biopsies by 52%, while detecting 92% of clinically significant cases compared with using PSA ≥3 ng/ml as a biopsy criterion. Both Stockholm3 and RPCRC exhibited strong discrimination, with area under the curve values of 0.80 (95% confidence interval [CI]: 0.76-0.85) and 0.75 (95% CI: 0.70-0.80), respectively. Stockholm3 demonstrated good calibration, while RPCRC underestimated the risk compared with observed outcomes. Moreover, Stockholm3 yielded positive clinical net benefits, whereas RPCRC yielded negative net benefits for clinically relevant thresholds. CONCLUSIONS AND CLINICAL IMPLICATIONS: Stockholm3 utilization could detect 92% of clinically significant prostate cancer cases while simultaneously reducing unnecessary biopsies by 52%, compared with the PSA ≥3 ng/ml criterion, based on our analysis within a cohort of men who underwent systematic biopsies. PATIENT SUMMARY: In a German clinical cohort of 405 men, Stockholm3, a blood test for early prostate cancer detection, exhibited favorable clinical benefits. It identified a substantial number of clinically significant cases while reducing unnecessary biopsies by over half in men without the disease and those with clinically nonsignificant prostate cancer.

The effect of adrenalectomy on overall survival in metastatic adrenocortical carcinoma.

CONTEXT: Although complete surgical resection provides the only means of cure in adrenocortical carcinoma (ACC), the magnitude of the survival benefit of adrenalectomy in metastatic ACC (mACC) is unknown. OBJECTIVE: To assess the effect of adrenalectomy on survival outcomes in patients with mACC in a real-world setting. DESIGN AND SETTING: Patients with mACC were identified within the Surveillance, Epidemiology, and End Results database (SEER 2004-2020) and we tested for differences according to adrenalectomy status. PATIENTS: Patients aged ≥18 years with metastatic ACC at initial presentation who were treated between 2004-2020. INTERVENTION: Primary tumor resection status (Adrenalectomy vs no-adrenalectomy). MAIN OUTCOME AND MEASURES: Kaplan-Meier plots, multivariable Cox regression models and landmark analyses were used. Sensitivity analyses focused on use of systemic therapy, contemporary (2012-2020) vs. historical (2004-2011), single vs. multiple metastatic sites and assessable specific solitary metastatic sites (lung only and liver only). RESULTS: Of 543 patients with mACC, 194 (36%) underwent adrenalectomy. In multivariable analyses, adrenalectomy was associated with lower overall mortality without (hazard ratio [HR]: 0.39; p<0.001), as well as with three months' landmark analyses (HR: 0.57, p=0.002). The same association effect with three months' landmark analyses was recorded in patients exposed to systemic therapy (HR: 0.49, p<0.001), contemporary patients (HR: 0.57, p=0.004), historical patients (HR: 0.42 , p<0.001), and in those with lung only solitary metastasis (HR: 0.50, p=0.02). In contrast, no significant association was recorded in patients naïve to systemic therapy (HR: 0.68, p=0.3), those with multiple metastatic sites (HR: 0.55, p=0.07) and those with liver only solitary metastasis (HR: 0.98, p=0.9). CONCLUSIONS: The current results indicate a potential protective effect of adrenalectomy in mACC, particularly in patients exposed to systemic therapy and those with lung-only metastases.

Postoperative Management of Prostate Cancer-Optimizing Prostate Cancer Care.

This Viewpoint discusses the end point analyses and results of the RACICALS-RT study.

Impact of homologous recombination repair/BReast CAncer (BRCA) gene alterations on survival in a real-world setting of metastatic prostate cancer.

OBJECTIVE: To investigate alterations of homologous recombination repair (HRR) and especially BReast CAncer 1/2 (BRCA1/2) gene on overall survival (OS). Moreover, to explore the effect of inhibition of poly(ADP-ribose)-polymerase (PARPi) as systemic therapy for metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: Of all HRR-screened patients with metastatic prostate cancer, baseline characteristics were sampled. Kaplan-Meier estimates and multivariable Cox regression models predicted the effect of HRR/BRCA1/2 alterations on OS. RESULTS: Of 196 eligible patients, 61 (31%) harboured any HRR and 40 (20%) BRCA1/2 alterations. Of HRR alterations, 40 (66%) vs six (10%) vs five (8.2%) vs four (6.6%) vs two (3.3%) vs four (6.6%) were BRCA1/2 vs Ataxia-telangiectasia mutated kinase (ATM) vs checkpoint kinase 2 (CHEK2) vs cyclin-dependent kinase 12 (CDK12) vs Fanconi anaemia complementation Group A (FANCA) vs positive for other mutations. Of these, 30% received a PARPi. OS differed significantly between HRR-positive vs -negative patients. Specifically in hormone-sensitive prostate cancer, the median OS was 63 (HRR positive) vs 57 (BRCA1/2 positive) vs 113 months (HRR negative) (P ≤ 0.01). In mCRPC, OS was 42 (HRR positive) vs 41 (BRCA1/2 positive) vs 70 months (HRR negative) (P ≤ 0.01). HRR and BRCA1/2 alterations were associated with worse OS after multivariable adjustment. Finally, patients with mCRPC with BRCA1/2 mutation treated without PARPi harboured worse OS than patients with BRCA1/2 mutation and PARPi therapy (median OS: 33 vs 48 months, P < 0.03). CONCLUSION: Incidence of HRR alteration in a clinical real-world setting is high when using blood- and tissue-based tests. Patients with HRR/BRCA alterations have worse outcomes resulting in significant OS differences between HRR/BRCA-positive patients with mCRPC with and without PARPi usage vs HRR/BRCA-negative patients.

Mortality Risk for Patients with Biopsy Gleason Grade Group 1 Prostate Cancer.

BACKGROUND AND OBJECTIVE: We investigated the association of clinical factors at presentation with the presence of unsampled high-risk prostate cancer (PC) and PC-specific mortality (PCSM) and all-cause mortality (ACM) following radical prostatectomy in patients with biopsy Gleason Grade Group (GGG) 1 PC. METHODS: The study population comprised 10228 patients treated for GGG1 PC diagnosed via transrectal ultrasound (TRUS)-guided systematic biopsy (SBx; n = 9248) or combined biopsy (CBx; SBx + TRUS/magnetic resonance image [MRI] fusion biopsy; n = 980) from a cohort study at a university hospital in Hamburg, Germany. We used logistic, Fine and Grays, and Cox multivariable regression methods to calculate the adjusted odds ratio (aOR) of adverse pathology and adjusted hazard ratios (aHRs) for early prostate-specific antigen (PSA) failure (≤18 mo), PCSM, and ACM in relation to each clinical factor. KEY FINDINGS AND LIMITATIONS: Irrespective of biopsy approach, percent positive biopsies (PPB) >50% and PSA >20 ng/ml were significantly associated with higher risk of adverse pathology (SBx: aOR 1.71 and 3.49; CBx: aOR 1.81 and 2.82, respectively) and early PSA failure (SBx: aHR 1.54 and 4.37; CBx: aHR 2.88 and 7.81, respectively). PPB >50% and PSA >20 ng/ml were also associated with higher risk of PCSM (aHRs 2.56 and 3.71) and ACM (aHRs 1.47 and 2.00) in the SBx group (all p ≤ 0.04). The study is limited by the single-institution cohort design. CONCLUSION AND CLINICAL IMPLICATION: Maintaining the "cancer" classification for patients with GGG1 and either PPB >50% or PSA>20 ng/ml and considering rebiopsy to identify unsampled high-grade disease may minimize the risk of mortality for this subgroup. PATIENT SUMMARY: For patients undergoing non-targeted prostate biopsy, approximately 1 in 12 with a biopsy result of grade group 1 prostate cancer may have more aggressive cancer than the result suggests. A very high PSA (prostate-specific antigen) level (>20 ng/ml) or the presence of grade group 1 cancer in more than 50% of the biopsy samples can identify patients at risk.

Contemporary Treatment Patterns and Oncological Outcomes of Metastatic Hormone-sensitive Prostate Cancer and First- to Sixth- line Metastatic Castration-resistant Prostate Cancer Patients.

Background and objective: With approval of novel systemic therapies within the past decade for metastatic hormone-sensitive (mHSPC) and castration-resistant (mCRPC) prostate cancer, patients may receive several therapy lines. However, the use of these treatments is under an ongoing change. We investigated contemporary treatment trends and progression-free (PFS) and overall (OS) survival of different therapy lines. Methods: Relying on our institutional tertiary-care database, we identified mHSPC and mCRPC patients. The main outcome consisted of treatment changes (estimated annual percentage change [EAPC]) within the past decade, as well as PFS and OS for different mHSPC and mCRPC treatment lines. Key findings and limitations: In 1098 metastatic patients, the median age was 70 yr with a median of two systemic therapy lines. For first-line mCRPC between 2013 and 2023, androgen deprivation monotherapy (ADT) monotherapy usage decreased significantly from 31% to 0% (EAPC -38.3%, p < 0.001), while the administration of chemotherapy increased from 16.7% to 33.3% (EAPC: +10.1%, p < 0.001). The PFS/OS rates of mHSPC patients was 21/67 mo, and those for first-, second-, third-, fourth-, fifth-, and sixth-line mCRPC patients were 11/47, eight of 30, seven of 24, six of 19, seven of 17, and seven of 13 mo, respectively. With an increased number of new combination therapy lines received, the median OS in mCRPC improved from 26 mo (one systemic treatment) to 52 mo (two or more lines of systemic treatment). Conclusions and clinical implications: Significant changes in treatment patterns could be observed for mHSPC and mCRPC patients within the past decade, and usage of ADT monotherapy has decreased rapidly in real-world practice. Moreover, PFS decreases significantly with every therapy line, and OS increases with the implementation of new therapies. Patient summary: Improvements in the real-world setting regarding the usage of combination therapies for metastatic hormone-sensitive and castration-resistant prostate cancer were made, which is reflected in contemporary survival outcomes.

Survival of patients with lymph node versus bone versus visceral metastases according to CHAARTED/LATITUDE criteria in the era of intensified combination therapies for metastatic hormone-sensitive prostate cancer.

BACKGROUND: The first approvals of novel systemic therapies within recent years for metastatic hormone-sensitive (mHSPC) were mainly based on improved overall survival (OS) and time to castration resistance (ttCRPC) in mHSPC patients stratified according to CHAARTED low (LV) versus high volume (HV) and LATITUDE low (LR) versus high-risk (HR) disease. METHODS: Relying on our institutional tertiary-care database we identified all mHSPC stratified according to CHAARTED LV versus HV, LATITUDE LR versus HR and the location of the metastatic spread (lymph nodes (M1a) versus bone (M1b) versus visceral/others (M1c) metastases. OS and ttCRPC analyses, as well as Cox regression models were performed according to different metastatic categories. RESULTS: Of 451 mHSPC, 14% versus 27% versus 48% versus 12% were classified as M1a LV versus M1b LV versus M1b HV versus M1c HV with significant differences in median OS: 95 versus 64 versus 50 versus 46 months (p < 0.001). In multivariable Cox regression models HV M1b (Hazard Ratio: 2.4, p = 0.03) and HV M1c (Hazard Ratio: 3.3, p < 0.01) harbored significant worse than M1a LV mHSPC. After stratification according to LATITUDE criteria, also significant differences between M1a LR versus M1b LR versus M1b HR versus M1c HR mHSPC patients were observed (p < 0.01) with M1b HR (Hazard Ratio: 2.7, p = 0.03) and M1c HR (Hazard Ratio: 3.5, p < 0.01), as predictor for worse OS. In comparison between HV M1b and HV M1c, as well as HR M1b versus HR M1c no differences in ttCRPC or OS were observed. CONCLUSIONS: Significant differences exist between different metastatic patterns of HV and LV and HR and LR criteria. Best prognosis is observed within M1a LV and LR mHSPC patients.

Cost Analysis of Prostate Cancer Care Using a Biomarker-enhanced Diagnostic Strategy with Stockholm3.

Background and objective: Building on previous research demonstrating better prostate cancer (PC) diagnostics via a biomarker-enhanced approach, this study focuses on cost analysis of PC care using the Stockholm3 test. We assessed the economic impact in European health care systems using real-world evidence for diagnostic outcomes and relevant costs. Methods: We evaluated two PC diagnostic strategies: (1) the conventional prostate-specific antigen (PSA) strategy with magnetic resonance imaging (MRI) and (2) PSA testing with a reflex to biomarkers at PSA ≥1.5 ng/ml in guiding decisions to perform MRI. Data from the Swedish National Prostate Cancer Register and Capio St. Göran Hospital provided real-world evidence, supplemented by health economic modeling. A comprehensive cost analysis was conducted using a Markov model for treatment pathways for four PC disease states and overall spending, for which costs from various European health care systems were used. A deterministic sensitivity analysis was performed across different cost and diagnostic scenarios. Key finding and limitations: The average cost for the four disease states was €2 182 for benign disease, €10 023 for low-grade disease, €13 073 for intermediate- to high-grade localized or locally advance disease, and €271 210 for metastatic disease. The overall spending was €358 239 (7.7%) lower per 1000 men tested in the biomarker-enhanced strategy in comparison to the PSA strategy. The primary cost saving was attributed to lower treatment expenses for metastatic disease. Sensitivity analysis affirmed the robustness of the findings across various diagnostic and treatment scenarios. Conclusions and clinical implications: Biomarker-enhanced diagnostic strategies may reduce health care costs for PC management and are likely to improve quality-adjusted life years in a scenario in which metastatic disease is reduced. Patient summary: We explored different ways to detect prostate cancer more cost-effectively. We found that using a specific blood test, called Stockholm3, after a PSA (prostate-specific antigen) test to decide if an MRI scan (magnetic resonance imaging) is necessary could save money, mainly by identifying localized cancer earlier and reducing the need for expensive treatments for advanced cancer.

Survival of stage III non-seminoma testis cancer patients versus simulated controls, according to race/ethnicity.

BACKGROUND: It is unknown whether 5-year overall survival (OS) differs and to what extent between the American Joint Committee on Cancer stage III non-seminoma testicular germ cell tumor (NS-TGCT) patients and simulated age-matched male population-based controls, according to race/ethnicity groups. METHODS: We identified newly diagnosed (2004-2014) stage III NS-TGCT patients within the Surveillance Epidemiology and End Results database 2004-2019. For each case, we simulated an age-matched male control (Monte Carlo simulation), relying on Social Security Administration (SSA) Life Tables with 5 years of follow-up. We compared OS rates between stage III NS-TGCT patients and simulated age-matched male population-based controls, according to race/ethnicity groups (Caucasian, Hispanic, Asian/Pacific Islander and African American). Both, cancer-specific mortality (CSM) and other-cause mortality (OCM) were computed. RESULTS: Of 2054 stage III NS-TGCT patients, 60% were Caucasians versus 33% Hispanics versus 4% Asians/Pacific Islanders versus 3% African Americans. The 5-year OS difference between stage III NS-TGCT patients versus simulated age-matched male population-based controls was highest in Asians/Pacific Islanders (64 vs. 99%, Δ = 35%), followed by African Americans (66 vs. 97%, Δ = 31%), Hispanics (72 vs. 99%, Δ = 27%), and Caucasians (76 vs. 98%, Δ = 22%). The 5-year CSM rate was highest in Asians/Pacific Islanders (32%), followed by African Americans (26%), Hispanics (25%), and Caucasians (20%). The 5-year OCM rate was highest in African Americans (8%), followed by Caucasians (4%), Asians/Pacific Islanders (4%), and Hispanics (2%). CONCLUSION: Relative to SSA Life Tables, the highest 5-year OS disadvantage applied to stage III NS-TGCT Asian/Pacific Islander race/ethnicity group, followed by African American, Hispanic and Caucasian, in that order.