Adjuvant chemotherapy does NOT improve BDFS rates in men with intermediate- and high-risk prostate cancer

With the third Advanced Prostate Cancer Consensus Conference (APCCC) due to start here in Basel, Switzerland, this morning, there is an important new set of data that will help to inform some of the discussions.

Kellokumpu-Lehtinen et al. have just reported the results of the Scandinavian Prostate Cancer Group study no. 13 (SPCG-13) in European Urology.

We have known for a while — from the CHAARTED study and from the STAMPEDE trial — that adding about six cycles of docetaxel chemotherapy (without any prednisone) to standard forms of treatment (e.g., androgen deprivation therapy [ADT] with or without radiation therapy) could significantly extend the survival of men with newly diagnosed, metastatic prostate cancer who had a high tumor burden.

We have also been aware that, in similar men with a relatively low tumor burden, adding docetaxel did not seem to offer the same level of benefit.

What the SPCG-13 trial set out to explore was whether early use of adjuvant docetaxel-based chemotherapy might delay biochemical recurrence of disease in men with intermediate- and high-risk forms of prostate cancer who were scheduled to receive treatment with a combination of radiation therapy and ADT.

Starting in 2007, a total of 376 patients were randomized to one or other of the following two forms of treatment:

  • Radiation therapy + ADT + docetaxel chemotherapy (Arm A, n = 188)
  • Radiation therapy + AST alone (Arm B, n = 188)

Note that patients with evident metastatic (M+) and/or node-positive (N+) disease were not eligible for inclusion in this trial.

The primary study endpoint was biochemical progression, defined by a rising PSA level to ≥ 2 ng/ml above the patient’s nadir PSA level. The patients were followed for 5 years by taking PSA levels every 3 months for 2 years and every 6 months for the remaining 3 years.

Here are the major findings from the study:

  • The average (median) age of study participants was 67 years in both of the treatment groups.
  • 75 percent of the patients had T3 disease.
  • 47 percent of the patients had a Gleason score of 8, 9, or 10.
  • The average (median) follow-up was 59 months (range, 1 to 111 months).
  • In Arm A, 147/188 patients (78 percent) completed all six cycles of docetaxel chemotherapy.
  • The primary endpoint of biochemical progression was observed in
    • 58 patients in Arm A
    • 57 patients in Arm B
  • Kaplan-Meier analysis showed no difference in the biochemical disease-free survival (BDFS) curves between the treatment groups (p = 0.6).
  • The 5-year estimated biochemical progression rates were
    • 31 percent of patients in arm A
    • 28 percent of patients in Arm B
  • Febrile neutropenia occurred in 16 percent of patients receiving docetaxel in Arm A.
  • There were no deaths associated with docetaxel treatment.
  • There were 43 deaths during the trial, including
    • 20 in arm A (of which 9 were due to prostate cancer)
    • 23 in arm B (of which 7 were due to prostate cancer)
  • The hazard ratio for PSA progression of Arm A compared to Arm B was 1.14 (p = 0.5).

The authors concluded that

Adjuvant docetaxel without prednisone did not improve BDFS after radical [radiation therapy] with ADT for intermediate- or high-risk [prostate cancer].

2 Responses

  1. I have a paper I compiled in this regard that has been published wherein, from my research, I note that adding docetaxel to ADT to men for whom metastasis is not yet evident resulted in those patients experiencing grade 3 or 4 hematologic toxic effects of neutropenia (60 of 125 patients [48.0%]), febrile neutropenia (10 [8.0%]), and thrombocytopenia (4 [3.0%]).

  2. They also presented this at ASCO last year.

    In addition, a Spanish randomized controlled trial had similar findings.

    But both of those looked at BCR as an endpoint. What about survival?

    GETUG-12 reported that metastasis-free survival, prostate cancer-specific survival, and overall survival were not significantly different (see here).

    RTOG 0521 reported a survival improvement with chemotherapy + RT, but the difference in survival, although statistically significant, was not meaningful: 4-year overall survival was 89% without docetaxel and 93% with it. But, there was a significant improvement in disease-free survival (65% vs. 55% at 6 years), and incidence of metastases at 6 years (9% vs 14%). It’s possible that with longer follow up, the difference in overall survival will increase in magnitude.

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