Neoadjuvant ADT prior to radical surgery in high-risk prostate cancer patients

A group of South Korean researchers have just reported data on the prevalence and outcomes of pT0 disease after neoadjuvant androgen deprivation therapy (ADT) and radical prostatectomy among men receiving first-line therapy for high-risk prostate cancer.

This study by Joung et al. was based on a retrospective analysis of a cohort of 111 South Korean patients, all of whom had D’Amico high-risk prostate cancer at diagnosis and were treated with at least 3 months of neoadjuvant ADT prior to a radical prostatectomy. (By D’Amico high-risk prostate cancer the authors meant that the patients had at least one of the following characteristics: a PSA level of ≥ 20 ng/ml, or a biopsy Gleason score of ≥ 4 + 4 = 8, or a clinical stage of ≥ T2c.)

They categorized the patients into two groups based on the pathological findings post surgery:

  • Patients whose pathological status was pT0 (see Table 1 of the study)
  • Patients whose pathological status was not pT0 (i.e., it was pT2a or higher)

Based on this classification they showed that

  • 6/111 patients (5.4  percent) were pT0 (i.e., there was no evidence of cancer in the prostate specimen post-surgery).
  • 105/111 patients (94.6 percent) were non-pT0 (i.e., there was evidence of cancer in the prostate specimen post-surgery).
  • During an average (median) follow-up period of 54 months for all 111 patients (range, 3 to 102 months),
    • There was no sign of recurrence of prostate cancer in the small group of six pT0 patients.
    • Biochemical recurrence was observed in 60/105 non-pT0 patients (57.1 percent), with a median time to recurrence of 14 months.
  • The six pT0 patients were older than the non-pT0 disease (p = 0.014) but there were no other significant differences between the two sets of patients (see Table 2 of the study).

This is one of the largest studies to date suggesting that a subset of patients with high-risk disease can potentially be cured by the combination of neoadjuvant ADT + radical prostatectomy … but there are three things that it does not tell us:

  • It cannot tell us that the patients were actually cured (because follow-up is too short).
  • It cannot tell us that the same six men with pT0 disease wouldn’t have been free of biochemical recurrence at 5.4 years of follow-up if they had not received neoadjuvant ADT.
  • It cannot tell us what the “correct” period of neoadjuvant ADT might be prior to surgery to optimize this type of outcome (because among the 6 men who had pT0 disease at time of surgery the period of neoadjuvant ADT varied from 3 to 12 months).

The best way to look at this study at this time is simply to say that it has once again demonstrated that there is a subset of high-risk patients whose cancer is found to be pT0 after neoadjuvant ADT + radical prostatectomy.

Joung et al. state that, at their institution, neoadjuvant ADT is administered prior to radical prostatectomy in patients with locally advanced and high-risk prostate cancer “at the surgeon’s discretion” (and hopefully with the patient’s informed consent). What we also need to acknowledge and appreciate is that such men are being exposed early to the additional risks associated with treatment with ADT. Whether such risks are really justified by the potential benefits is still not known at the present time.

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