Kupelian P A, Klein E A, Witte J S, Kupelian V A, Suh J H
Department of Radiation Oncology, Cleveland Clinic Foundation, Case Western Reserve University, Ohio 44195, USA.
J Urol. 1997 Dec;158(6):2197-201. doi: 10.1016/s0022-5347(01)68194-1.
We analyzed the outcome after radical prostatectomy of patients with familial prostate cancer versus patients with sporadic prostate cancer.
The study included 720 patients with prostate carcinoma who were treated with prostatectomy between 1987 and 1996. Patients were excluded from the study if they had received adjuvant or neoadjuvant treatment, or had no available pretreatment prostatic specific antigen (PSA) level, no available biopsy Gleason score, incomplete pathological information or no available followup PSA levels. The analysis was performed on 529 cases. Patients were considered to have a positive family history for prostate cancer when the index patient confirmed the diagnosis of prostate cancer in a first degree relative (brother or father). The outcomes of interest were biochemical relapse-free survival, local failure and distant metastases. Proportional hazards were used to analyze the effect of family history and confounding variables (that is age, stage, biopsy Gleason score, initial PSA levels, surgical specimen Gleason score, extracapsular extension, lymph node metastasis, seminal vesicle invasion and surgical margin involvement) on treatment outcome.
Median followup was 30 months. Of all cases 12% had a positive family history. Younger age was the only factor associated with positive family history, with 18% of patients younger than 65 years having a positive family history versus 6% of older patients (chi-square p <0.001). The 5-year biochemical relapse-free survival rate for the entire group was 64%. The 5-year biochemical relapse-free survival rates for patients with negative family history versus positive history were 66% and 46%, respectively (p = 0.001). A multivariate time-to-failure analysis using the proportional hazards model was performed based on family history, age (less than 65 versus 65 to 69 versus 70 or greater, initial PSA (10 or less versus greater than 10), biopsy Gleason score (6 or less versus 7 or greater), clinical T stage (T1-T2A versus T2B-C), prostatectomy specimen Gleason score (6 or less versus 7 or greater), extracapsular extension, seminal vesicle involvement, surgical margin involvement and lymph node involvement. After adjusting for the potential confounding factors, positive family history remained strongly associated with biochemical failure. The clinical failure rate for the entire group was 14%. The 5-year local failure rate was 7%, with positive surgical margins being the only independent predictor of local failure. The 5-year distant metastasis rate was 8%, with family history and initial PSA levels being independent predictors of distant relapse.
Our study suggests that patients with a familial prostate cancer have a higher likelihood of biochemical failure after radical prostatectomy than patients with sporadic cancer. This effect is independent of pretreatment or pathological factors. Our results suggest that the higher failure rates associated with familial prostate cancer are mainly secondary to higher distant relapse rates, and that familial prostate cancer may be more biologically aggressive than sporadic cancers.
我们分析了家族性前列腺癌患者与散发性前列腺癌患者根治性前列腺切除术后的结局。
本研究纳入了1987年至1996年间接受前列腺切除术的720例前列腺癌患者。若患者接受过辅助或新辅助治疗、无术前前列腺特异性抗原（PSA）水平、无活检Gleason评分、病理信息不完整或无随访PSA水平，则被排除在研究之外。对529例病例进行了分析。当索引患者确诊一级亲属（兄弟或父亲）患有前列腺癌时，该患者被认为有前列腺癌家族史阳性。感兴趣的结局为生化无复发生存率、局部失败和远处转移。采用比例风险模型分析家族史和混杂变量（即年龄、分期、活检Gleason评分、初始PSA水平、手术标本Gleason评分、包膜外侵犯、淋巴结转移、精囊侵犯和手术切缘受累）对治疗结局的影响。
中位随访时间为30个月。所有病例中12%有家族史阳性。年龄较小是与家族史阳性相关的唯一因素，65岁以下患者中有18%家族史阳性，而65岁及以上患者为6%（卡方检验p<0.001）。整个组的5年生化无复发生存率为64%。家族史阴性与阳性患者的5年生化无复发生存率分别为66%和46%（p = 0.001）。基于家族史、年龄（小于65岁与65至69岁与70岁及以上）、初始PSA（10或更低与大于10）、活检Gleason评分（6或更低与7或更高）、临床T分期（T1-T2A与T2B-C）、前列腺切除标本Gleason评分（6或更低与7或更高）、包膜外侵犯、精囊受累、手术切缘受累和淋巴结受累，使用比例风险模型进行多变量失败时间分析。在调整潜在混杂因素后，家族史阳性仍与生化失败密切相关。整个组的临床失败率为14%。5年局部失败率为7%，手术切缘阳性是局部失败的唯一独立预测因素。5年远处转移率为8%，家族史和初始PSA水平是远处复发的独立预测因素。
我们的研究表明，家族性前列腺癌患者根治性前列腺切除术后生化失败的可能性高于散发性癌症患者。这种影响独立于术前或病理因素。我们的结果表明，与家族性前列腺癌相关的较高失败率主要继发于较高的远处复发率，并且家族性前列腺癌可能比散发性癌症在生物学上更具侵袭性。
