Radiation therapy for localized prostate cancer in men with diabetes mellitus


A new paper recently published on line in Urology (“the Gold Journal”) suggests that men with diabetes who are treated with curative intent for localized prostate cancer using external beam radiation therapy may experience higher than normal risk for late genitourinary complications and adverse effects.

Kalakota and Liauw looked at data on a large group of men with a prior diagnosis of diabetes mellitus who were subsequently diagnosed with localized prostate cancer and treated with external beam radiation therapy between 1988 and 2008. Their goal was to investigate the influence of diabetes — if any — on late genitourinary and gastrointestinal toxicity.

Here are the key data from their study, which was based on retrospective data review, so this was not a prospective clinical trial:

  • The study cohort comprised 626 patients, all treated by external beam radiation therapy
    • 30 percent of the men had low-risk disease.
    • 42 percent had intermediate-risk disease.
    • 28 percent had high-risk disease
  • The average (median) total dose of radiation was 74 Gy.
  • 45 percent of the patients received androgen deprivation therapy (ADT) for a median of 4 months.
  • The median follow-up period was 55 months.
  • 102/626 patients (16 percent) had diabetes.
    • 8 percent of the patients (8/102) were able to controlled their diabetes by  diet modification.
    • 52 percent of the patients (54/102) controlled their diabetes by use of oral medications.
    • 39 percent of the patients (40/102) contolled their diabetes by use of insulin injections.
  • Compared to the non-diabetics, patients with diabetes were
    • More likely to receive ADT in conjunction with intensity-modulated radiation therapy
    • More likely to have to have a shorter follow-up duration (P ≤ 0.05 for all).
  • On the basis of univariate analysis
    • A higher total dose of radiation dose, greater baseline urinary dysfunction, the use of intensity-modulated radiation therapy, and a prior diagnosis of diabetes were all associated with grade 2 or higher levels of genitourinary toxicity.
    • Transurethral resection of the prostate and a prior diagnosis of diabetes were associated with grade 3 or higher levels of genitourinary toxicity.
    • The use of ADT, age ≥ 70 years, and anticoagulation therapy were all associated with grade 2 or higher levels of genitourinary toxicity.
    • Age ≥ 70 years and anticoagulation therapy were associated with grade 3 or higher levels of genitourinary toxicity.
  • On the basis of multivariate analysis
    • A prior diagnosis of diabetes was associated with  greater risk of grade 2 or higher (relative risk 1.36, P = 0.10) and grade 3 or higher levels of genitourinary toxicity (relative risk 2.74, P = 0.04).

Kalakota and Liauw conclude that a higher incidence of late genitourinary toxicity was evident in the patients with a prior diagnosis of diabetes; that this relationship might be useful when considering the treatment of prostate cancer among patients with diabetes; and that this relationship might be especially significant among men with diabetes who were considering dose-escalated external beam radiation therapy or those who had a prior history of transurethral resection of the prostate.

Now it should be said that there has been a major transformation in the way that radiation therapy can be delivered and is actually applied over the time period of this study (i.e. from 1988 to 2008). One therefore has to be cautious in interpreting these data and considering their actual relevance to — say — a 68-year-old man with diabetes diagnosed today with a PSA of 7 ng/ml, clinical stage T2b prostate cancer, and a Gleason score of 3 + 4 = 7. Such a patient may already not be a good candidate for the use of neoadjuvant ADT because of the pre-existing diabetes, but the current study does not tell us a great deal about how to determine an appropriate dose of radiation therapy than can eliminate his prostate cancer with otherwise minimal effects on his genitourinary functionality.

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