THE "NEW" PROSTATE CANCER INFOLINK

New data from the ongoing STAMPEDE trial in the UK and Switzerland has now confirmed that ablative radiation of the prostate itself (debulking of the primary tumor) improves overall survival (OS) in men newly diagnosed with metastatic prostate cancer who have a low metastatic disease burden but not in those with higher burden of disease. These data come from a presentation just given by Parker et al. at the ongoing ESMO 2018 Congress in Munich, Germany (see this media release, issued by ESMO).

It has long been suspected that elimination of the primary tumor (by surgery, or by radiation therapy, or by other means) might improve local control of prostate cancer in men newly diagnosed with metastatic disease and slow progression of the metastatic disease itself. Parker et al. decided to test the hypothesis that radiation to the prostate would improve OS in men initially diagnosed with metastatic prostate cancer and that the survival benefit would be more evident in men with a relatively low metastatic burden.

Newly diagnosed men with metastatic, hormone-sensitive prostate cancer in this arm of the STAMPEDE trial were therefore randomized to either

• Standard care, with lifelong androgen deprivation therapy (ADT), with early docetaxel also permitted from 2016 onwards (SOC) or
• SOC + radiation therapy to the prostate on one or other of two schedules (administered as 55 Gy in 20 fractions over 4 weeks or as 36 Gy in 6 fractions over 6 weeks)

Initial, stratified randomization (to SOC or SOC + radiation therapy) was carried out within 12 weeks of initiation of ADT. Radiation therapy was initiated ≤ 8 weeks after initial randomization or completion of docetaxel chemotherapy.

The primary outcome measure was OS (i.e., death from any cause); secondary outcomes included failure-free survival (FFS). Pre-specified subgroup analysis allowed for testing of the effects of the two treatments based on metastatic burden at study entry. A higher burden of metastatic disease was defined by any one of

• ≥ 4 bone metastases with at least one outside the axial skeleton
• ≥ 4 bone metastases with at least one outside the axial skeleton and visceral metastasis
• Visceral metastasis alone

Here are the core study findings:

• 2,061 men with newly-diagnosed TxNxM1 prostate cancer were randomized between January 2013 and September 2016.
• The average (median) age of the patients was 68 years.
• Levels of metastatic burden were as follows:
  • 40 percent of patients had a low metastatic burden
  • 54 percent of patients had a higher metastatic burden
  • In 6 percent of patients the metastatic burden was unknown
• Compared to SOC alone, the addition of localized radiation to the prostate had the following impact:
  • Among all patients,
    • It improved FFS (hazard ratio [HR] =0.76)
    • It did not improve OS (HR = 0.92)
  • It improved OS (HR = 0.68) among 819 men with low metastatic burden
  • It did not improve OS among 1,120 men with higher metastatic burden (HR = 1.07)
• Therapy was generally well tolerated both
  • During SOC + radiation therapy (when 5 percent of patients had Grade 3 or 4 adverse events)
  • After completion of SOC + radiation therapy (when 4 percent of patients had Grade 3 or 4 adverse events)
  • After completion of SCO (when < 1 percent of patients had Grade 3 or 4 adverse events)

Parker et al. concluded that

Radiotherapy to the prostate did not improve survival for unselected patients with newly-diagnosed metastatic prostate cancer, but, in a pre-planned analysis, did improve survival in men with a lower metastatic burden. Therefore, prostate radiotherapy should be a standard treatment option for men with oligometastatic disease.

Speaking on behalf of ESMO, Prof. Karim Fizazi, commented that:

For the first time, this study provides evidence that treating the local primary tumor is associated with improvement in overall survival in men with metastatic prostate cancer and minimal disseminated disease.”

He added that the finding that there was no significant increase in OS in men with higher burden of disease was in line with the previously reported data.

Prof. Fizazi also suggested that:

For men with newly diagnosed oligometastatic prostate cancer, it is quite likely that [these] data [are] practice changing. … For men with higher burden of disease more data are needed regarding whether upfront local treatment improves or prevents local symptoms, which, by itself, may justify its use in the absence of an overall survival benefit.

However, Prof. Fizazi did also note the following as limitations of this study:

• Only 18% of the patients received early docetaxel.
• No patients received early abiraterone acetate (Zytiga)

It is worth remembering that, in the original CHAARTED trial, it was the men newly diagnosed with metastatic prostate cancer and with a higher disease burden who showed a better level of response to ADT + docetaxel than the men with a lower disease burden. So there are still unanswered questions about the potential for use of ADT + docetaxel and/or abiraterone acetate + radiation therapy in men newly diagnosed with hormone-sensitive, metastatic prostate cancer. The same may be the case for the use of other combinations (e.g., ADT + docetaxel and/or enzalutamide + radiation therapy) in this group of men.

Filed under: Diagnosis, Living with Prostate Cancer, Management, Treatment | Tagged: ADT, androgen, debulking, deprivation, docetaxel, metastasis, primary, radiation, therapy, tumor |