Abiraterone and Increased Survival in Metastatic Prostate Cancer

Prior Chemotherapy ◽

This chapter summarizes the findings of a landmark trial conducted in men with castrate-resistant prostate cancer who had received prior chemotherapy comparing abiraterone to placebo. It demonstrated improved progression-free and overall survival. It was relatively well tolerated, with most adverse effects related to mineralocorticoid excess.

Enzalutamide in Metastatic Prostate Cancer Before Chemotherapy

50 Studies Every Urologist Should Know ◽

10.1093/med/9780190655341.003.0018 ◽

2021 ◽

pp. 101-106

Author(s):

Joseph Zabell

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Radiographic Progression ◽

Progression Free Survival ◽

Cytotoxic Chemotherapy ◽

Free Survival ◽

Prior Chemotherapy ◽

This chapter summarizes the findings of the landmark PREVAIL trial conducted in men with castrate-resistant prostate cancer who had received prior chemotherapy comparing enzalutamide to placebo. It demonstrated improved overall survival, radiographic progression-free survival, and time to cytotoxic chemotherapy.

Patterns of response to androgen deprivation therapy in younger patients with locally advanced or metastatic prostate cancer.

10.1200/jco.2018.36.6_suppl.324 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 324-324

Author(s):

Matthew Keating ◽

Lisa Giscombe ◽

Andre Desouza ◽

Shiva Kumar Reddy Mukkamalla ◽

Ritesh Rathore

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Androgen Deprivation Therapy ◽

Locally Advanced ◽

Androgen Deprivation ◽

Standards Of Care ◽

National Cancer Database ◽

324 Background: Androgen deprivation therapy (ADT) remains a standard of care in the treatment of locally advanced prostate cancer. But thanks to a few key trials (STAMPEDE, CHAARTED, and LATITUDE) reported within the past three years, docetaxel and abiraterone now have roles in extending overall survival in a patient population traditionally treated with ADT alone. These treatments when combined with ADT have been shown to extend overall survival in metastatic hormone-sensitive prostate cancer patients. The role of ADT in relation to other therapies continues to evolve rapidly. We intend to revisit ADT’s longstanding role in prostate cancer treatment using a national cancer database. Our aim is to look beyond traditional standards of care to identify patients more likely to have overall survival benefit from ADT. Are there any subgroups of patients with intermediate or high risk disease that have improved survival outcomes with androgen deprivation therapy, besides patients with localized disease that underwent radiation? Could there be other variables besides PSA and localization of the prostate cancer that should be considered when identifying ADT treatment candidates, or identifying survival trends in these groups? Methods: We are currently analyzing variables present in the National Cancer Database to retrospectively identify predictive factors for overall survival and progression to metastatic castrate resistant prostate cancer in locally advanced prostate cancers treated with ADT. We will evaluate time-to-death from the initiation of ADT and from the diagnosis of metastatic castrate resistant prostate cancer. The following variables in localized, locally advanced, and metastatic prostate cancer will be analyzed with Statistical Analysis Software: age, locally advanced, site-specific metastasis (M1a, M1b, M1c), Gleason score, local treatment (radical prostatectomy or radiation), stage (T, N, and M), prostate lobe (one vs. both; T2a/b vs. T2c), chemotherapy (date, time from M1 stage), comorbidity score, ethnicity, facility type, insurance, and risk groups (low/intermediate/high as per NCCN guidelines).

Radium-223 in the treatment of metastatic castrate-resistant prostate cancer: A real-world Irish experience.

10.1200/jco.2020.38.6_suppl.228 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 228-228

Author(s):

Niamh Peters ◽

John Gaffney ◽

Emma Connolly ◽

Richard Bambury ◽

Derek Gerard Power ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Alkaline Phosphatase ◽

Real World ◽

Median Number ◽

Prior Chemotherapy ◽

Factors Associated ◽

Radium 223 ◽

228 Background: Radium 223 (Ra-223) has been successfully utilised in the trial setting for the treatment of men with metastatic castrate resistant prostate cancer (mCRPC). To date, no real world outcomes from its use in the Irish population have been described. Methods: From September 2016 to March 2019, data from men referred for Ra-223 treatment at our institution was retrospectively collected. We recorded patient characteristics, treatments received and outcomes. Overall Survival (OS) was analysed using the Kaplan-Meier method. Results: 81 men were referred for Ra 223. Complete data was available for 56 men. Median age was 75. 79%(45/56) had over 6 bone metastases and 21%(12/56) had lymph node involvement. The median number of prior systemic treatments for mCRPC was 2. 84%(47/56) of patients were previously treated with Androgen deprivation therapy (ADT); 48%(27/56) Abiraterone, 36%(20/56) Docetaxel, 45%(25/56) Enzalutamide and 9%(5/56) Cabazitaxel. All patients were receiving bone protection agents; 57%(32/56) Zolendronic acid and 43%(24/56) Denosumab. Median ECOG was 1 at the start of treatment and 2 at completion. The median number of treatments received was 4 with 36%(20/56) completing all 6 treatments. The most common toxicity seen was grade1 fatigue occurring in10% (6/56). 17% (10/56) required a blood transfusion during their treatment course. 53%(30/56) required opioid analgesia prior to Ra 223 treatment. 76% of these men (22/30) described improved pain following Rad-223. At a median follow up of 13 months,41%(23/56) were alive. The median OS for the entire group was 7 months. Factors associated with improved OS included ECOG 0-1,fewer than 6 bone metastases, normal alkaline phosphatase level at start of treatment and no prior chemotherapy use. Median OS for those who had not received prior chemotherapy was significantly better than those who had (9 vs 5 months p=0.04). Conclusions: This real world study demonstrates Ra 223 is a well tolerated palliative treatment amongst Irish men with mCRPC. Good performance status, lower alkaline phosphatase, chemotherapy naivety and a low burden of metastatic disease are factors associated with an improved overall survival.

Management of Advanced and Metastatic Prostate Cancer: A Need for a Sub-Saharan Guideline

Journal of Oncology ◽

10.1155/2019/1785428 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Ayun Cassell ◽

Bashir Yunusa ◽

Mohamed Jalloh ◽

Medina Ndoye ◽

Mouhamadou M. Mbodji ◽

...

Keyword(s):

Prostate Cancer ◽

Androgen Deprivation Therapy ◽

Cost Effective ◽

Androgen Deprivation ◽

Sub Saharan Africa ◽

International Agency ◽

Sub Saharan ◽

The estimated incidence rate of prostate cancer in Africa was 22.0/100,000 in 2016. The International Agency for Research on Cancer (IARC) has cited prostate cancer as a growing health threat in Africa with approximated 28,006 deaths in 2010 and estimated 57,048 deaths in 2030. The exact incidence of advanced and metastatic prostate cancer is not known in sub-Saharan Africa. Hospital-based reports from the region have shown a rising trend with most patients presenting with advanced or metastatic disease. The management of advanced and metastatic prostate cancer is challenging. The available international guidelines may not be cost-effective for an African population. The most efficient approach in the region has been surgical castration by bilateral orchidectomy or pulpectomy. Medical androgen deprivation therapy is expensive and may not be available. Patients with metastatic castrate-resistant prostate cancer tend to be palliated due to the absence or cost of chemotherapy or second-line androgen deprivation therapy in most of Africa. A cost-effective guideline for developing nations to address the rising burden of advanced prostate cancer is warranted at this moment.

A National Multicenter Study on overall survival in elderly metastatic castrate-resistant prostate cancer patients treated with Radium-223

Aging Clinical and Experimental Research ◽

10.1007/s40520-020-01573-5 ◽

2020 ◽

Author(s):

Viviana Frantellizzi ◽

Fabio Monari ◽

Manlio Mascia ◽

Renato Costa ◽

Giuseppe Rubini ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Cancer Patients ◽

Multicenter Study ◽

Radium 223 ◽

Early prostate-specific antigen response post-abiraterone as predictor of overall survival in metastatic castrate-resistant prostate cancer

BMC Cancer ◽

10.1186/s12885-019-5729-7 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 5

Author(s):

Joshua P. Schiff ◽

Patrick Cotogno ◽

Allison Feibus ◽

Peter Steinwald ◽

Elisa Ledet ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Prostate Specific Antigen ◽

Specific Antigen ◽

Castrate Resistant ◽

Response Post

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

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 ◽

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]

Addition of carboplatin to chemotherapy regimens for metastatic castrate-resistant prostate cancer in post-second generation hormone therapy setting: Does it improve treatment response and survival outcomes?

10.1200/jco.2020.38.15_suppl.e17540 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e17540-e17540

Author(s):

Jamal Alamiri ◽

Mohamed E. Ahmed ◽

Jack R. Andrews ◽

Manaf Alom ◽

Giovanni Motterle ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Hormone Therapy ◽

Disease Progression ◽

P Value ◽

Versus Group ◽

Group A ◽

Castrate Resistant ◽

Group B

e17540 Background: The clinical course in metastatic castrate-resistant prostate cancer (mCRPC) can be complicated when patients have disease progression after treatment with 2nd generation hormone therapy (2nd-HT), such as enzalutamide or abiraterone. Currently, limited data exist regarding the optimal choice of chemotherapy for mCRPC after failing 2nd-HT. We sought to evaluate three common chemotherapy regimens in this setting. Methods: We retrospectively identified 150 patients with mCRPC with disease progression on enzalutamide or abiraterone. 92 patients were chemo-naïve, while 58 patients had previously received docetaxel chemotherapy prior to 2nd-HT. After failing 2nd-HT, 90 patients received docetaxel-alone (group A), 33 patients received carboplatin plus docetaxel (group B), while 27 patients received cabazitaxel-alone (Group C). Favorable response was defined by ≥50% reduction in PSA level from baseline after a complete course of chemotherapy. Survival outcome was assessed for 30-month overall survival. Results: Mean (SD) age was 71.2 (8.28), 69.5(8.38) and 67.2 (8.36) for group (A), (B) and (C), respectively. Mean (SD) pre-chemotherapy PSA was 63.8 (138.18), 58.5 (118.15) and 53.7 (88.15) for group (A), (B) and (C), respectively. Mean (SD) Gleason score was 7.9 (1.1), 8.4 (0.88) and 8.1 (1.06) for group (A), (B) and (C), respectively. Patients in group (B) were 2.6 times more likely to have a favorable response compared to group (A) (OR = 2.625, 95%CI: 1.15 - 5.99) and almost 3 times compared to patients in group (C) (OR = 2.975, 95%CI: 1.04 – 8.54) (p-value = 0.0442). We report a Hazard Ratio (HR) of 3.1 (95% CI 1.31-7.35; p = 0.0037) between patients in group (A) versus group (B), and a HR of 4.18 (95% CI 1.58-11.06; p = 0.0037) between patients in group (C) versus group (B). Thirty-month overall survival was 70.7%, 38.9%, and 30.3% for group (B), (A), and (C) respectively (p-value = 0.008). Conclusions: Our data demonstrate improved response and cancer-specific survival in patients with treatment-refractory mCRPC on docetaxel plus carboplatin compared to docetaxel or cabazitaxel alone. Selection bias is inherent in any retrospective study; however, our finding suggests that clinicians may consider docetaxel plus carboplatin in mCRPC patients who fail 2nd-HT. Further prospective studies are warranted.

Genetics of Prostate Carcinoma

Acta Medica Academica ◽

10.5644/ama2006-124.327 ◽

2021 ◽

Vol 50 (1) ◽

pp. 71

Author(s):

Božo Krušlin ◽

Lucija Škara ◽

Tonći Vodopić ◽

Borna Vrhovec ◽

Jure Murgić ◽

...

Keyword(s):

Prostate Cancer ◽

Prostate Carcinoma ◽

Poor Prognosis ◽

Large Scale ◽

Genetically Engineered ◽

Genetically Engineered Mouse Models ◽

Genomic Studies ◽

The aim of this review is to provide a brief overview of some current approaches regarding diagnostics, pathologic features, treatment, and genetics of prostate carcinoma (PCa). Prostate carcinoma is the most common visceral tumor and the second most common cancer-related cause of death in males. Clinical outcomes for patients with localized prostate cancer are excellent, but despite advances in prostate cancer treatments, castrate-resistant prostate cancer and metastatic prostate cancer patients have a poor prognosis. Advanced large-scale genomic studies revealed a large number of genetic alterations in prostate cancer. The meaning of these alterations needs to be validated in the specific prostate cancer molecular subtype context. Along these lines, there is a critical need for establishing genetically engineered mouse models, which would include speckle type BTB/POZ protein and isocitrate Dehydrogenase (NADP (+)) 1 mutant, as well as androgen receptor neuroendocrine subtypes of prostate cancer. Another urgent need is developing highly metastatic prostate cancer models, as only up to 17% of available models dis- play bone metastases and exhibit a less typical neuroendocrine prostate cancer or sarcomatoid carcinoma. Moreover, androgen deprivation and relapse should be mimicked in the genetically engineered mouse models, as androgen independence may yield a better model for metastatic castrate-resistant prostate cancer. The development of such refined animal models should be guid- ed by comparative genomics of primary versus corresponding metastatic tumors. Such an approach will have the potential to illuminate the key genetic events associated with specific molecular prostate cancer subsets and indicate directions for effective therapy.Conclusion. Despite excellent results in the treatment of localized prostatic carcinoma, castrate-resistant prostate can- cer and metastatic prostate cancer have a poor prognosis. Advanced large-scale genomic studies revealed a large number of ge- netic alterations in PCa. Experimental models of prostate carcinoma in genetically modified mice could provide new data about the genetic changes in such cancers and help in developing better animal models for treatment resistant prostate carcinomas.