Urinary symptom flare after brachytherapy for prostate cancer is associated with erectile dysfunction and more urinary symptoms before implantation

Abstract

To examine the relationship of 'symptom flare' with sexual function and lower urinary tract symptoms (LUTS) before brachytherapy, as we noted that after brachytherapy for prostate cancer, some patients had recurrent LUTS after an asymptomatic period; this secondary exacerbation of symptoms ('symptom flare') occurred at approximately 2 years after implantation and was transient in most patients. In all, 854 patients with organ-confined prostate carcinoma had transrectal ultrasonography-guided transperineal 125I interstitial brachytherapy of the prostate gland between June 1991 and September 2002, and were considered candidates for this study. Detailed information on urinary function was self-administered and prospectively collected before treatment and at intervals using the International Prostate Symptom Score (IPSS). Sexual function was evaluated with the Sexual Health Inventory for Men (SHIM), a five-question, self-administered diagnostic test that can help to indicate the presence or absence of erectile dysfunction (ED). We used previously established criteria to estimate the risk of prostate-specific antigen (PSA) failure by dividing the men into three risk groups, i.e. low-risk, with a PSA level of < or = 10 ng/mL, stage < or = T2a, Gleason < or = 6; medium-risk, with a PSA level of < or = 15 ng/mL, Gleason 7 or stage T2b; and high-risk, with a PSA level of > 15 ng/mL, stage > T2b, or Gleason > or = 8. There was a significant association of flare with ED; men with flare reported significantly more ED than men without (P = 0.020). Men with high-risk disease reported more ED because they received more intensive treatment (hormones and increased radiation dose) than men with medium- or low-risk disease. To correct for this confounding factor, multivariate linear regression was used; the regression was significant overall (P < 0.001), and the effects of risk group (P < 0.001) and flare (P < 0.026) on SHIM score were significant and independent of each other. Flare was also significantly associated with a higher pre-implant IPSS; the probability of flare was 62% for a pre-implant IPSS of zero, to 94% for an IPSS of 30. Radiation reaction and radiation sensitivity contribute to ED and greater LUTS in men who have had brachytherapy for prostate cancer. This contribution is evident, e.g. in men with ataxia-telangiectasia (ATM) gene mutations. Sequence variants in the ATM gene, particularly those that encode for an amino-acid substitution, are associated with adverse radiotherapy responses among patients treated with 125I prostate brachytherapy. Our finding of the association of urinary symptom flare with ED suggests it would be worthwhile to determine whether sildenafil is as effective in men with flare, and if not, whether higher sildenafil doses would be of value. Alternatively, alpha1-selective adrenoceptor-blocking agents, e.g. terazosin, combined with sildenafil, might be of benefit. Also, patients with a high IPSS before brachytherapy can be warned that they have a greater risk of flare and ED.