Second-line treatment for men with radiorecurrent prostate cancer (the FORECAST trial)


An ongoing clinical trial available exclusively in the UK is the so-called FORECAST trial, designed to investigate focal forms of second-line therapy for men with progressive, radiorecurrent prostate cancer after first-line treatment with external beam radiation therapy.

Historically, the vast majority of men with radiorecurrent prostate cancer after initial radiation therapy have been treated with androgen deprivation therapy (ADT). Second-line surgery tends to be associated with his risk for complications and side effects (but may be appropriate in selected cases). In recent years, however, we have seen the use of both cryotherapy and high-intensity focused ultrasound (HIFU) used to treat some men with radiorecurrent prostate cancer at selected centers.

The FORECAST trial — described here on the ClinicalTrials.gov web site and also in an article by Kanthabalan et al. — has been designed to explore both novel mechanisms of diagnostic evaluation of men who have radiorecurrent disease and  focal salvage therapy for an appropriate subset of patients.

Appropriately selected patients must

  • Have prostate cancer previously treated by external beam radiotherapy with or without neoadjuvant/adjuvant hormone therapy
  • Be in biochemical failure as defined by the Phoenix criteria (PSA nadir + 2 ng/ml)
  • Be considering or willing to consider local salvage treatment for radiorecurrent disease
  • Have a life expectancy of ≥5 years

One can not participate in this trial if

  • You have taken any form of hormone therapy (except 5-alpha reductase inhibitors) within the previous 6 months.
  • Your PSA doubling time is ≤ 3 months.
  • Your total PSA level is ≥ 20 ng/ml.
  • You have had prostate biopsies following biochemical failure.

All appropriate patients undergo a whole-body, multi-parametric MRI scan (WB-MRI), an [11C]choline PET/CT scan, a standard bone scan, and a pelvic multi-parametric MRI scan (mpMRI). They are also given an MRI-guided, transperineal targeted biopsy (MRI-TB) and a transperineal template prostate mapping biopsy (TP-MB). Patients who — based on these evaluations — are considered to be suitable for focal salvage therapy are then treated using either focal HIFU or focal cryotherapy.

The trial has a series of primary outcome measures, as follows:

  • The accuracy of WB-MRI to detect distant metastatic disease
  • The accuracy of prostate mpMRI in local detection of radiorecurrent prostate cancer
  • The accuracy of MRI-TB in detection of local disease
  • The rate of urinary incontinence following focal salvage therapy.

The hypothesis is that focal salvage therapy may be associated with lower risk for side effects and complications of treatment while offering a high level of disease control. However, as the trialists fully recognize, if one is to be able to deliver focal salvage therapy with accuracy, you’d better be able to detect the presence of prostate cancer (local, regional, and metastatic) with a high degree of accuracy.

The trial has been designed to enroll about 180 patients, not all of whom will be good candidates for focal salvage therapy. The hope is that the trial will be completed by early 2016. The best way to think about a trial like this is as a pilot study rather than a full-blown trial of effectiveness and safety of focal salvage therapy. However, the level of efficacy of the pilot study may depend heavily on just how many patient prove to be good candidates for focal salvage.

It is perhaps regrettable that no centers outside the UK are currently participating in this study. However, conversely, if one does live in the UK, and one does find one has radiorecurrent prostate cancer after first-line treatment with radiation therapy, one might well want to ask one’s urologist or radiation oncologist for a referral to one of the centers enrolling patients into this trial!

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