Modern 5-year outcome data after radiotherapy for very high-risk patients

A newly published paper reports 5-year outcome data from a series of men initially diagnosed with very high-risk, but localized prostate cancer — all of whom were treated with either dose-escalated external beam radiation therapy (EBRT) or pelvic radiation + permanent interstitial seed implantation (combined modality radiotherapy or CMRT).

Shilkrut et al. carried out a retrospective, multi-institutional review encompassing exclusively patients diagnosed with at least two out of the three factors defining D’Amico high-risk prostate cancer (i.e., a PSA level >20 ng/ml, a Gleason score of 8 to 10, or a clinical stage of T3/T4 disease). As indicated above, all patients were treated by dose-escalated EBRT or by CMRT.

Although this is not specified in the abstract, it would be our assumption that all the patients in this study were diagnosed no earlier than 2004, and therefore represent a relatively “modern” set of very high-risk patients.

Here are the study findings:

  • The study included data from a total of 238 patients.
    • 164/238 patients (69 percent) were treated by dose-escalated EBRT.
    • 74/238 patients(31 percent) were treated by CMRT.
  • Most patients (209/238 or 88 percent) also received adjuvant androgen deprivation therapy (ADT).
    • 133/238 patients (56 percent) received ADT for ≥ 24 months (i.e., long-term ADT).
  • Most patients (69 percent) were > 65 years of age.
  • Patients > 65 years of age were less likely to receive CMRT than younger patients (25 vs. 43 percent, P = 0.006).
  • Average (median) patient follow-up was 61 months.
  • Outcomes for all patients were
    • A median biochemical progression-free survival (bPFS) of 50.6 ± 4.7 percent
    • A median distant metastasis-free survival (DMFS) of 68.5 ± 4.3 percent
    • A median prostate cancer-specific survival (PCSS) of 78.7 ± 3.8 percent
    • These outcomes were similar for all patients, regardless of age.
  • On multivariate analysis (after adjustment for patient, tumor, and treatment-related covariates)
    • CMRT was associated with an improved bPFS (HR = 0.44, P=0.012) and with trends favoring improved rates of DMFS (HR = 0.52, P = 0.10) and CSS (HR = 0.55, P = 0.21).
    • Long-term ADT was independently associated with improved rates of bPFS (HR = 0.40, P = 0.019), CSS (HR = 0.20, P = 0.002), and prostate cancer-specific mortality (HR = 0.25, P = 0.004).

It is clear from this study that both dose-escalated EBRT and CMRT — particularly when combined with 2+ years of ADT — are capable of inducing long-term remissions and 5+ years of prostate cancer-specific survival in this group of very high-risk patients. However, it is also clear that about half of these patients are probably going to demonstrate biochemical progression within 5 years.

3 Responses

  1. Since my profile fits right into this study with very high-risk disease (as defined above), CMRT and > 24 months of hormone therapy (HT), the results are of particular note to me.

    I would be very interested to learn what the study learned from the PSA patterns post termination of HT. There have been very few studies, if any, and anecdotal experience, based on myself and a couple of others, is that the PSA rises for some time before dropping.

    I do not have access to the study to see what they documented.

  2. Show this to the, eh, doctor, who excluded me from a similar trimodal scheme but with very high dose escalation for the HDR brachytherapy, and see what the guy says. Better yet, ask his then boss in the Dutch Health Ministry, all servants of American private insurers since 1 January 2006. I was diagnosed in December 2008, excluded from the brachy part on demonstrably false grounds, moved to a more rational society, and seem to have survived.

  3. @Rick. I think I lost your e-mail address. I’d be glad to send you the study if I can copy it. If I cannot find the address I will let the sitemaster know.

    The PSA rise and fall is called the PSA “bounce”. It occurs frequently, often several years after treatment. If the PSA rises for about 9 months, continues to rise, and trends above a fixed value, then extra tests are called for. I forget the values used here in Uppsala, but can check.

    NOW, on second thought, can you e-mail me so that I can reply quickly? That would be helpful to me.

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