Role of Second-Line Systemic Treatment Post-Docetaxel in Metastatic Castrate Resistant Prostate Cancer- Current Strategies and Future Directions

While androgen-targeted therapies are routinely used in advanced prostate cancer (PCa), their effect is poorly understood in treating bone metastatic lesions and ultimately results in the development of metastatic castrate resistant prostate cancer (mCRPC). Here, we used an all-human microtissue-engineered model of mineralized metastatic tissue combining human osteoprogenitor cells, 3D printing and prostate cancer cells, to assess the effects of the antiandrogens, bicalutamide, and enzalutamide in this microenvironment. We demonstrate that cancer/bone stroma interactions and antiandrogens drive cancer progression in a mineralized microenvironment. Probing the bone microenvironment with enzalutamide led to stronger cancer cell adaptive responses and osteomimicry than bicalutamide. Enzalutamide presented with better treatment response, in line with enzalutamide delaying time to bone-related events and enzalutamide extending survival in mCRPC. The all-human microtissue-engineered model of mineralized metastatic tissue presented here represents a substantial advance to dissect the role of the bone tumor microenvironment and responses to therapies for mCPRC.

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Radium 223 treatment in metastatic castrate-resistant prostate cancer: Impact of sequencing on survival—Real-world outcomes from a single United Kingdom center.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.7_suppl.223 ◽

2019 ◽

Vol 37 (7_suppl) ◽

pp. 223-223 ◽

Cited By ~ 1

Author(s):

Xue Yan Jiang ◽

Sarah Atkinson ◽

Sam Cuming ◽

Alexander Burns ◽

Rachel Anne Pearson ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Marrow ◽

Bone Metastasis ◽

Systemic Treatment ◽

Survival Outcomes ◽

Prior Chemotherapy ◽

Radium 223 ◽

Castrate Resistant Prostate Cancer ◽

Castrate Resistant ◽

The Impact

223 Background: Radium 223 (Ra-223) is a FDA and EMA approved alpha particle radiopharmaceutical used to treat men with metastatic castrate resistant prostate cancer (mCRPC) with symptomatic bone metastasis. In view of emerging systemic options, new EMA 2018 licence indication is for 3rd line onwards. We aim to evaluate the impact of systemic therapy sequencing on survival outcomes from a heterogeneous cohort of 228 patients treated with Ra-223 in a single UK centre. Methods: We prospectively collected data from 228 men underwent Ra-223 therapy for mCRPC between April 2014 and August 2018. Survival outcomes in relation to sequence of systemic treatment used prior to Ra-223 were analysed. Results: Medium age = 72 (51-87) years. Most patients (n = 142, 69%) received at least one systemic agent prior to Ra-223: docetaxel and/or cabaxitaxel chemotherapy (n = 60, 29%), abiraterone (n = 62, 30.1%) and enzalutamide (n = 67, 32.5%) in various sequences. No patients received concurrent Ra-223 /systemic treatment other than LHRH analogue. Key findings are summarized in table below. Conclusions: Our data demonstrated better survival trend in patients who received Ra-223 early. Patients who received prior chemotherapy have worse survival compared with those who were chemo-naïve likely due to bone marrow depletion. Ra-223 should not be offered to patients who have already had both cabaxitaxel and docetaxel as their medium survival is too poor to justify a treatment which takes 6 months to complete.[Table: see text]

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PSA values as a surrogate of overall survival (OS) in metastatic castrate resistant prostate cancer (mCRPC) treated with second-line (2L) chemotherapy (CT).

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.15_suppl.e16104 ◽

2014 ◽

Vol 32 (15_suppl) ◽

pp. e16104-e16104

Author(s):

Martin Richardet ◽

Matias Nicolas Cortes ◽

Matias Molina ◽

Patricia Hernandez ◽

Romina Brombin ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Second Line ◽

Castrate Resistant Prostate Cancer ◽

Castrate Resistant

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Liquid Biopsies in Castrate-Resistant Prostate Cancer: Future Prospects in Radiation Oncology

10.47890/jcrat/2020/gcarlos/18041702 ◽

2020 ◽

Vol 1 (1) ◽

Author(s):

Carlos Galvis ◽

María Caicedo Martinez

Keyword(s):

Prostate Cancer ◽

Radiation Oncology ◽

Liquid Biopsies ◽

Castrate Resistant Prostate Cancer ◽

Pre Treatment ◽

Castrate Resistant ◽

Molecular Patterns ◽

Available Information

The use of liquid biopsies, based on circulating tumor cells and tumoral DNA, provides information on the molecular patterns and genomics of Castrate-Resistant Prostate Cancer. There is evidence on the role of the androgen receptor variant 7 as a prognostic and as a follow-up tool, especially as a follow-up to treatment response and resistance with Enzalutamide and Abiraterone. Little is known about the genomics of Castrate Resistant Prostate Cancer and its relationship to radiation therapy’s sensibility. This is particularly relevant for patients with oligometastatic disease, who could obtain a long control of the disease with radiation. In this narrative review, we summarize the available information on liquid biopsies and Castrate Resistant Prostate Cancer. As radiation oncology evolves towards Genomically Adapted Radiation Dose, the role of liquid biopsies as a possible pre-treatment assessment is a future target. Nonetheless, models have been modeled after other malignancies. This highlights the need for further studies to assess the use of personalized medicine in these patients. Keywords: Radiotherapy; Prostate Cancer; Receptors Androgen; Liquid Biopsy; Precision Medicine;

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Potential role of rituximab in metastatic castrate-resistant prostate cancer

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155218790338 ◽

2018 ◽

Vol 25 (6) ◽

pp. 1509-1511 ◽

Cited By ~ 4

Author(s):

Poorva Bindal ◽

Sharif AA Jalil ◽

Lisa M Holle ◽

Jessica M Clement

Keyword(s):

Prostate Cancer ◽

B Cell ◽

Disease Progression ◽

Androgen Deprivation ◽

Cell Infiltration ◽

Prostate Cells ◽

Develop Disease Progression ◽

Castrate Resistant Prostate Cancer ◽

Castrate Resistant

Nearly all men with prostate cancer who are treated with androgen deprivation therapy develop disease progression. There is considerable evidence to suggest that CXCL 13 released by tumor cells leads to B-cell infiltration into the prostate cells. This B-cell infiltration has been postulated to play a role in development of disease progression following androgen-deprivation therapies. We present a case of a patient who achieved remission of metastatic castrate-resistant prostate cancer after receiving rituximab and bendamustine for the treatment of follicular lymphoma. The findings in this report suggest that further investigation is warranted for utilizing B-cell targeted therapy in delaying progression of castrate-resistant prostate cancer.

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