Lehrer Steven, Cesaretti Jamie, Stone Nelson N, Stock Richard G
Department of Radiation Oncology, Mount Sinai Medical Center, New York 10029, USA.
BJU Int. 2006 Nov;98(5):979-81. doi: 10.1111/j.1464-410X.2006.06398.x.
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.
我们注意到，前列腺癌近距离放射治疗后，一些患者在无症状期后会出现下尿路症状（LUTS）复发；这种症状的二次加重（“症状突发”）发生在植入后约2年，且大多数患者为一过性。本研究旨在探讨近距离放射治疗前“症状突发”与性功能及下尿路症状（LUTS）之间的关系。
1991年6月至2002年9月期间，共有854例局限性前列腺癌患者接受了经直肠超声引导下经会阴125I前列腺间质近距离放射治疗，并被纳入本研究。治疗前及随访期间，患者通过国际前列腺症状评分（IPSS）自行填写并前瞻性收集详细的排尿功能信息。性功能采用男性性健康量表（SHIM）进行评估，该量表包含5个问题，由患者自行填写，可用于判断是否存在勃起功能障碍（ED）。我们采用先前制定的标准，将患者分为三个风险组，即低风险组（PSA水平≤10 ng/mL，分期≤T2a，Gleason评分≤6）、中风险组（PSA水平≤15 ng/mL，Gleason评分7或分期T2b）和高风险组（PSA水平＞15 ng/mL，分期＞T2b，或Gleason评分≥8），以评估前列腺特异性抗原（PSA）失败的风险。
症状突发与ED之间存在显著关联；有症状突发的男性报告的ED明显多于无症状突发的男性（P = 0.020）。高风险组患者报告的ED更多，因为他们比中风险组或低风险组患者接受了更强化的治疗（激素治疗和增加放射剂量）。为校正这一混杂因素，我们采用了多元线性回归分析；总体回归具有显著性（P < 0.001），风险组（P < 0.001）和症状突发（P < 0.026）对SHIM评分的影响均具有显著性，且相互独立。症状突发还与植入前较高的IPSS显著相关；植入前IPSS为零的患者症状突发的概率为62%，IPSS为30的患者症状突发的概率为94%。
放射反应和放射敏感性导致接受前列腺癌近距离放射治疗的男性出现ED和更严重的LUTS。这种影响很明显，例如在患有共济失调毛细血管扩张症（ATM）基因突变的男性中。ATM基因的序列变异，特别是那些编码氨基酸替代的变异，与接受125I前列腺近距离放射治疗的患者放疗不良反应相关。我们发现排尿症状突发与ED之间存在关联，这表明有必要确定西地那非对有症状突发的男性是否同样有效，如果无效，更高剂量的西地那非是否有价值。或者，α1选择性肾上腺素能受体阻滞剂，如特拉唑嗪，与西地那非联合使用可能有益。此外，对于近距离放射治疗前IPSS较高的患者，可以告知他们症状突发和ED的风险更高。
