Clinical trial NCT06145958: Radiotherapy and Androgen Deprivation In Combination After Local Surgery (RADICALS) Translational Study
Official title: A Translational Study of Samples From the Radiotherapy and Androgen Deprivation In Combination After Local Surgery (RADICALS) Prostate Cancer Trial to Identify Those Most Likely to Benefit From Androgen Deprivation With Salvage Radiotherapy
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Prostate Cancer
Keywords: biomarker
Lead sponsor: University College, London
Sponsor class: OTHER
First posted: 2023-11-24
Enrollment: 2585
Sex: MALE
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients were recruited to the RADICALS trial at one of two points:

RT - after surgery for prostate cancer, possessing one or a number of higher risk features for subsequent relapse. These patients were randomised to either immediate radiotherapy or deferred until the point of biochemical relapse.

HD - at the point of intiation of radiotherapy in the adjuvant or salvage setting. These patients were randomised to a number of different androgen deprivation durations (as detailed above in the cohort descriptions).

Brief summary: The goal of this translational study is to test the use of biomarkers in salvage treatment for prostate cancer after a previous operation to remove the prostate. The main question it aims to answer is:

• Can a biomarker identify a group of patients most likely to benefit from androgen deprivation therapy in conjunction with salvage radiotherapy No new participants will be involved, but tumour samples will be acquired, for patients that gave their permission in the completed RADICALS RT and HD studies.

Detailed description: Early prostate cancer represents a wide spectrum of disease. Indolent disease is unlikely to ever become symptomatic and treatment is needlessly morbid and costly. Aggressive disease warrants intensification of therapy. Current clinical methods are poor at discriminating these outcomes.

The RADICALS trial was the largest trial conducted to date in men requiring further curative treatment after an operation. It already defined the role for radiotherapy after surgery (prostatectomy). The standard of care is now for blood test (PSA) monitoring after prostatectomy with radiotherapy offered when the PSA rises. The role and duration of hormone treatment (androgen deprivation), given in combination with radiotherapy, remains less clear. Currently if androgen deprivation is to be given, the RADICALS data support the use of a 24-month course, but this entails a considerable burden of side-effects for patients. Pathological and biological markers are needed to identify those most likely to benefit from androgen deprivation.

In RADICALS-TR, the investigators will conduct translational analyses on the biopsy and prostatectomy specimens from the RADICALS trial. The investigators aim to identify prognostic features and biomarkers predictive of benefit from androgen therapy. The investigators will prioritise the refinement and validation of clinical biomarkers already close to clinical utilisation. In this way it is hoped that findings can rapidly translate to stratified clinical trials and improved patient care.

Eligibility criteria: DISEASE CHARACTERISTICS:

Inclusion criteria:

Diagnosis of nonmetastatic adenocarcinoma of the prostate Must have undergone radical prostatectomy Post-operative serum prostate-specific antigen (PSA) \< 0.4 ng/mL No post-operative biochemical failure, defined as EITHER two consecutive rises in PSA and final PSA \> 0.1 ng/mL OR three consecutive rises in PSA (for patients undergoing hormone therapy duration randomization)

Exclusion criteria:

Known distant metastases from prostate cancer PSA \> 5 ng/mL at the time of hormone randomization (for patients undergoing hormone therapy duration randomization)

PATIENT CHARACTERISTICS:

* No other active malignancy likely to interfere with protocol treatment or follow-up.
* Consent has been given within the RADICALS (RT/HD) trial to translational research and follow up.

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

See Disease Characteristics Co-enrollment to other trials is permitted, providing this does not interfere with the outcome measures 5-α reductase inhibitors, soya, selenium, and vitamin E are acceptable non-trial therapies

Exclusion criteria:

Prior hormone therapy Bilateral orchidectomy Prior pelvic radiotherapy Neoadjuvant treatment Other concurrent therapies for prostate cancer (e.g., estrogens or cytotoxic chemotherapy) prior to disease progression

Primary outcomes:
measure: Freedom from Distant Metastases
timeFrame: Up to 12 years
Secondary outcomes:
measure: Overall survival
timeFrame: Up to 12 years
measure: Disease Specific Survival
timeFrame: Up to 12 years
measure: Freedom from treatment failure
timeFrame: Up to 12 years
measure: Clinical Progression Free survival
timeFrame: Up to 12 years
measure: Non protocol hormone therapy
timeFrame: Up to 12 years
measure: Freedom from biochemical progression
timeFrame: Up to 12 years
Other outcomes:
Locations:
Study officials:
affiliation: UCL
name: Matthew W Fittall, BMBCh PhD
role: PRINCIPAL_INVESTIGATOR
References: