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

Wenzel, Mike; Siech, Carolin; Hoeh, Benedikt; Koll, Florestan; Humke, Clara; Tilki, Derya; Steuber, Thomas; Graefen, Markus; Banek, Séverine; Kluth, Luis A.; Chun, Felix K.H.; Mandel, Philipp

doi:10.1016/j.euros.2024.06.010

European Urology Open Science

2024

DOI: 10.1016/j.euros.2024.06.010

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

Mike Wenzel,

Carolin Siech,

Benedikt Hoeh

et al.

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Cited by 5 publications

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Androgen receptor pathway inhibitors vs. docetaxel chemotherapy for metastatic hormone-sensitive and first-line castration resistant prostate cancer

Wenzel,

Hoeh,

Humke

et al. 2024

World J Urol

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Purpose No currently available phase III trial compared docetaxel vs. androgen receptor pathway inhibitors (ARPI) regarding cancer-control outcomes in metastatic hormone-sensitive prostate cancer (mHSPC). Moreover, few is known about the effect of sequential therapies in mHSPC and subsequent metastatic castration resistant prostate cancer (mCRPC). Methods We relied on the FRAMCAP database and compared docetaxel vs. ARPI in mHSPC patients regarding time to mCRPC (ttCRPC) and overall survival (OS). Sensitivity analyses addressed high volume mHSPC patients. Finally, sequential therapies were compared regarding progression-free survival (PFS) and OS in first-line mCRPC. Results Of 419 included mHSPC patients, 25% received docetaxel vs. 75% ARPI. ARPI patients were significantly older (71 vs. 66 years), and harbored lower baseline PSA (38 vs. 183 ng/ml, both p ≤ 0.002). Median ttCRPC was significantly longer for ARPI than for docetaxel-treated patients (30 vs. 17 months, hazard ratio [HR]: 0.49, p < 0.001). In OS analyses, ARPI patients also exhibited significantly longer OS, relative to docetaxel patients (96 vs. 50 months, HR: 0.67, p = 0.03). After multivariable adjustment in Cox regression models, no difference between both treatments remained in both analyses (all p > 0.05). In sensitivity analyses of high volume mHSPC patients only, also no ttCRPC or OS differences were observed for ARPI vs. docetaxel (all p > 0.05). Regarding sequential therapies, no PFS and OS differences were observed for all and specifically high volume mHSPC patients, when ARPI-ARPI vs. ARPI-docetaxel vs. docetaxel-ARPI treatments were compared (all p > 0.05). Conclusion In real-world setting, ARPI treatment performs comparable to docetaxel chemotherapy in mHSPC. Therefore, docetaxel should only be used in triplet therapy. Moreover, no differences for sequential therapies of ARPI/docetaxel combinations in first-line mCRPC were observed.

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Androgen receptor pathway inhibitors vs. docetaxel chemotherapy for metastatic hormone-sensitive and first-line castration resistant prostate cancer

Wenzel,

Hoeh,

Humke

et al. 2024

World J Urol

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Administration and cancer-control outcomes of bone-modifying agents in real-world patients with metastatic castration-resistant prostate cancer

Wenzel,

Hoeh,

Humke

et al. 2024

JBMR Plus

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Hormonal agents administered for metastatic castration-resistant prostate cancer may lead to osteoporosis, skeletal events, reduced quality of life and even reduced overall survival. Bone-modifying agents may prevent from those events but their effect on cancer-control outcomes remain uncertain. Relying on our institutional tertiary-care database to explore the effect of bone-modifying agents (bisphosphonates such as zoledronic acid and denosumab) on OS and progression-free survival in metastatic castration-resistant prostate cancer patients with at least one bone metastasis in Kaplan-Meyer estimates and Cox regression models. Of 420 metastatic castration-resistant prostate cancer patients, 60% received bone-modifying agents, which were younger (68 vs. 69 years) with more systemic treatment lines for mCRPC (3 vs. 2) and higher proportion of initial DeNovo metastatic disease (72% vs. 62%, all P≤.04) than patients without bone-modifying agents. In progression-free survival analyses, no significant differences were observed between both groups. In overall survival analyses, significant median overall survival differences were observed in favor of patients with bone-modifying agents (58 vs. 45 months, hazard ratio [HR]: 0.66), even after multivariable adjustment (HR: 0.37, both P≤.01). In bone-modifying agent-stratified analyses, 57% received denosumab vs. 43% bisphosphonates, with a significant higher rate of Eastern Cooperative Oncology Group status ≥2 patients in the bisphosphonates group. In progression-free and overall survival analyses, no significant differences were observed between bisphosphonates vs. denosumab patients, with numeric better results in progression-free survival analysis for denosumab after adjusting for covariates. Cumulative rate of osteonecrosis of the jaw at any treatment time was 12% in both groups and significantly decreased over time. Real-world data suggest a relatively low administration rate of bone-modifying agents in osseous metastatic castration-resistant prostate cancer patients. However, real-world also suggest an overall survival benefit, when bone-modifying agents are used, even after controlling for possible confounding patient and tumor characteristics.

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Cancer-Control Outcomes of Patients With Metastatic Castration-Resistant Prostate Cancer With BRCA Gene or Tumor Suppressor Mutations Undergoing 177-Lutetium Prostate-Specific Membrane Antigen Radioligand Therapy

Wenzel,

Koll,

Hoeh

et al. 2024

JCO Precis Oncol

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PURPOSE Several tumor gene mutations are known for metastatic castration-resistant prostate cancer (mCRPC). The individual response to 177-lutetium prostate specific membrane antigen radioligand therapy (Lu-PSMA) is under current investigation regarding the genomic profile of patients with mCRPC. MATERIALS AND METHODS We relied on the FRAMCAP database and compared progression-free survival (PFS) and overall survival (OS) rates of patients with mCRPC with breast cancer–related antigen ( BRCA ) or tumor suppressor gene mutations ( TP53 , PTEN , RB1 ). Specifically, subgroup analyses were performed for patients with Lu-PSMA–treated mCRPC. RESULTS Of 194 patients with mCRPC, 22% was BRCA1/2 versus 14% PTEN/TP53/RB1 versus 63% without one of these mutations. Patients with no mutation harbored a significantly lower Gleason score of 8-10, relative to BRCA and PTEN/TP53/RB1 patients. In PFS analyses of first-line mCRPC, no difference between all three groups was observed, whereas the median OS differed significantly with 46.3 versus 48.7 versus 95.4 months for BRCA versus PTEN/TP53/RB1 versus no mutated patients ( P < .05). In univariable Cox regression models, BRCA-mutated patients were at higher risk of death (hazard ratio, 2.57; P < .01), whereas PTEN/TP53/RB1 patients were not ( P = .4). Of 87 patients with Lu-PSMA–treated mCRPC, significant differences in PFS and OS were observed (both P ≤ .02). In univariable and multivariable Cox regression models, BRCA-mutated Lu-PSMA patients were at higher risk of death, whereas PTEN/TP53/RB1 patients had similar outcomes as no mutated patients. CONCLUSION In real-world setting, substantially lower OS in mCRPC is observed for BRCA - and PTEN/TP53/RB1 -mutated patients, whereas no difference in first-line PFS could be computed. In Lu-PSMA–treated patients, worst outcomes were observed for BRCA patients.

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

Cited by 5 publications

References 29 publications

Androgen receptor pathway inhibitors vs. docetaxel chemotherapy for metastatic hormone-sensitive and first-line castration resistant prostate cancer

Androgen receptor pathway inhibitors vs. docetaxel chemotherapy for metastatic hormone-sensitive and first-line castration resistant prostate cancer

Administration and cancer-control outcomes of bone-modifying agents in real-world patients with metastatic castration-resistant prostate cancer

Cancer-Control Outcomes of Patients With Metastatic Castration-Resistant Prostate Cancer With BRCA Gene or Tumor Suppressor Mutations Undergoing 177-Lutetium Prostate-Specific Membrane Antigen Radioligand Therapy

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