Additional Treatments to the Local tumour for metastatic prostate cancer-Assessment of Novel Treatment Algorithms (IP2-ATLANTA): protocol for a multicentre, phase II randomised controlled trial.

Published on Feb 25, 2021in BMJ Open2.692
· DOI :10.1136/BMJOPEN-2020-042953
Martin J. Connor11
Estimated H-index: 11
,
Taimur T. Shah15
Estimated H-index: 15
(Imperial College London)
+ 33 AuthorsNatalia Klimowska-Nassar2
Estimated H-index: 2
(Imperial College London)
Sources
Abstract
Introduction Survival in men diagnosed with de novo synchronous metastatic prostate cancer has increased following the use of upfront systemic treatment, using chemotherapy and other novel androgen receptor targeted agents, in addition to standard androgen deprivation therapy (ADT). Local cytoreductive and metastasis-directed interventions are hypothesised to confer additional survival benefit. In this setting, IP2-ATLANTA will explore progression-free survival (PFS) outcomes with the addition of sequential multimodal local and metastasis-directed treatments compared with standard care alone. Methods A phase II, prospective, multicentre, three-arm randomised controlled trial incorporating an embedded feasibility pilot. All men with new histologically diagnosed, hormone-sensitive, metastatic prostate cancer, within 4 months of commencing ADT and of performance status 0 to 2 are eligible. Patients will be randomised to Control (standard of care (SOC)) OR Intervention 1 (minimally invasive ablative therapy to prostate±pelvic lymph node dissection (PLND)) OR Intervention 2 (cytoreductive radical prostatectomy±PLND OR prostate radiotherapy±pelvic lymph node radiotherapy (PLNRT)). Metastatic burden will be prespecified using the Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease (CHAARTED) definition. Men with low burden disease in intervention arms are eligible for metastasis-directed therapy, in the form of stereotactic ablative body radiotherapy (SABR) or surgery. Standard systemic therapy will be administered in all arms with ADT±upfront systemic chemotherapy or androgen receptor agents. Patients will be followed-up for a minimum of 2 years. Primary outcome: PFS. Secondary outcomes include predictive factors for PFS and overall survival; urinary, sexual and rectal side effects. Embedded feasibility sample size is 80, with 918 patients required in the main phase II component. Study recruitment commenced in April 2019, with planned follow-up completed by April 2024. Ethics and dissemination Approved by the Health Research Authority (HRA) Research Ethics Committee Wales-5 (19/WA0005). Study results will be submitted for publication in peer-reviewed journals. Trial registration number NCT03763253; ISCRTN58401737
References62
Newest
#1Martin J. Connor (Imperial College London)H-Index: 11
#2Ailbe Smith (Imperial College London)H-Index: 1
Last. Hashim U. Ahmed (Imperial College London)H-Index: 64
view all 7 authors...
Abstract Context Metastasis-directed therapy (MDT) in the form of stereotactic ablative radiation therapy (SABR), or in combination with surgical metastasectomy, may have a role in cancer control and disease progression. Objective To perform a systematic review of MDT (surgery or SABR) for oligometastatic (up to 10 metastases, recurrent or de novo) hormone-sensitive prostate cancer in addition to or following primary prostate gland treatment. Evidence acquisition Medline, Embase, Cochrane Review...
Source
•PIVOTALboost evaluates benefits/toxicity of pelvic node RT and focal boost dose escalation.•Unfavourable intermediate/high risk and bulky local disease are most likely to benefit.•Functional MRI imaging is used to select patients for different types of dose escalation.•HDR brachytherapy or focal dose escalation with IMRT are used as options.•Training and support is provided to reduce variations of contouring and radiotherapy planning.•The trial is recruiting patients in 38 radiotherapy centres ...
Source
#1Martin J. Connor (Imperial College London)H-Index: 11
#2Taimur T. Shah (Imperial College London)H-Index: 15
Last. Hashim U. Ahmed (Imperial College London)H-Index: 64
view all 20 authors...
TPS5600Background: Local cytoreductive and metastasis-directed interventions are hypothesised to confer additional survival benefit beyond standard systemic therapy in patients with de novo synchro...
Source
#1Ryan Phillips (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 9
#2William Shi (Stanford University)H-Index: 11
Last. Curtiland Deville (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 25
view all 26 authors...
Importance Complete metastatic ablation of oligometastatic prostate cancer may provide an alternative to early initiation of androgen deprivation therapy (ADT). Objective To determine if stereotactic ablative radiotherapy (SABR) improves oncologic outcomes in men with oligometastatic prostate cancer. Design, Setting, and Participants The Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer (ORIOLE) phase 2 randomized study accrued participants from 3 US radiation tr...
Source
#1Ashley E. Ross (Johns Hopkins University)H-Index: 55
#2Paula J. Hurley (Johns Hopkins University)H-Index: 22
Last. Emmanuel S. Antonarakis (Johns Hopkins University)H-Index: 65
view all 12 authors...
Monotherapy with immune checkpoint inhibitors has generally been unsuccessful in men with advanced prostate cancer. Preclinical data support the notion that cryotherapy may improve immune-mediated and anti-tumor responses. The objective of this study was to assess the safety and feasibility of whole-prostate gland cryotherapy combined with pembrolizumab and androgen deprivation in men with oligometastatic hormone-sensitive prostate cancer. This single-institution, pilot trial recruited 12 patien...
Source
#1Martin J. Connor (Imperial College London)H-Index: 11
#2Taimur T. Shah (Imperial College London)H-Index: 15
Last. Hashim U. Ahmed (Imperial College London)H-Index: 64
view all 6 authors...
In the past decade, a revolution in the treatment of metastatic prostate cancer has occurred with the advent of novel hormonal agents and life-prolonging chemotherapy regimens in combination with standard androgen-deprivation therapy. Notwithstanding, the use of systemic therapy alone can result in a castrate-resistant state; therefore, increasing focus is being placed on the additional survival benefits that could potentially be achieved with local cytoreductive and/or metastasis-directed thera...
Source
#1Martin J. Connor (Imperial College London)H-Index: 11
#2M. Winkler (Imperial College London)H-Index: 2
Last. Hashim U. Ahmed (Imperial College London)H-Index: 64
view all 3 authors...
Source
#1Martin J. Connor (Imperial College London)H-Index: 11
#2Mathias Winkler (Imperial College London)H-Index: 17
Last. Hashim U. Ahmed (Imperial College London)H-Index: 64
view all 3 authors...
Source
#1Vincent Khoo (University of Melbourne)H-Index: 64
The management of oligometastatic prostate cancer continues to stimulate as well as vex cancer professionals since the concept was raised more than two decades ago. The use of regular prostate-specific antigen (PSA) monitoring together with advances in imaging technology such as combined positron-emission tomography (PET)/computed tomography (CT) has enable earlier identification of potential initial spread of disease and recurrence. Recent systematic reviews and trials have supported the feasib...
Source
Abstract Background Focal cryotherapy can be used to treat patients with clinically significant nonmetastatic prostate cancer to reduce side effects. Objective Early-medium-term cancer control and functional outcomes. Design, setting, and participants A prospective registry-based case series of 122 consecutive patients undergoing focal cryotherapy between October 1, 2013, and November 30, 2016, in five UK centres. Median follow-up was 27.8mo [interquartile range (IQR) 19.5–36.7]. A total of 35 p...
Source
Cited By1
Newest
#1Martin J. ConnorH-Index: 11
#2Mesfin G Genie (Aberd.: University of Aberdeen)H-Index: 4
Last. Tzveta Pokrovska (Imperial College Healthcare)
view all 21 authors...
Introduction null Systemic therapy with androgen deprivation therapy (ADT) and intensification with agents such as docetaxel, abiraterone acetate and enzalutamide has resulted in improved overall survival in men with de novo synchronous metastatic hormone-sensitive prostate cancer (mHSPC). Novel local cytoreductive treatments and metastasis-directed therapy are now being evaluated. Such interventions may provide added survival benefit or delay the requirement for further systemic agents and asso...
Source
#1Shuaishuai Fan (Shanxi Medical University)
#2Zheng Wang (Shanxi Medical University)
Last. Jingqi Wang (Shanxi Medical University)
view all 6 authors...
Prostate cancer (PCa) is the second most common malignancy in men, but its exact pathogenetic mechanisms remain unclear. This study explores the effect of enhancer RNAs (eRNAs) in PCa. Firstly, we screened eRNAs and eRNA -driven genes from The Cancer Genome Atlas (TCGA) database, which are related to the disease-free survival (DFS) of PCa patients;. screening methods included bootstrapping, Kaplan-Meier (KM) survival analysis, and Pearson correlation analysis. Then, a risk score model was establ...
Source
This website uses cookies.
We use cookies to improve your online experience. By continuing to use our website we assume you agree to the placement of these cookies.
To learn more, you can find in our Privacy Policy.