PSA正常的前列腺癌患者临床特点分析北大核心

目的:根据PSA低于4 ng/mL的前列腺患者的临床资料及随访情况,探讨此类前列腺癌患者的临床特点,对PSA正常的前列腺癌患者的诊断及治疗提供临床思路。方法:收集2013年01月至2018年01月西京医院及西安交通大学第二附属医院收治的35例PSA正常的前列腺癌患者的临床资料。观察此类患者的发病情况、临床就诊特征、病理学特征、危险程度分级、Gleason评分、治疗及预后。总结PSA正常的前列腺癌患者的临床诊断及治疗特征。结果:PSA正常的前列腺癌患者占同期确诊前列腺癌的5.72%。35例患者中,28例主要因为排尿困难为症状就诊,血清PSA 0.91~3.96 ng/mL,平均(2.73±0.77)ng/mL。f/tPSA>0.16为5例,占14.3%,前列腺体积平均值为(68.4±36.66)cm^(3),12例患者行磁共振检查,10例报告提示前列腺癌可能,2例报告为前列腺增生,未发现前列腺癌影像学证据。13例患者行B超引导下经直肠前列腺穿刺活检术,11例患者病理诊断为前列腺癌,2例患者未发现肿瘤证据。行经尿道前列腺电切术共24例,其中包括2例穿刺活检未发现肿瘤证据患者,并于术后12周行前列腺癌根治性手术。病理结果显示:29例为前列腺腺癌,2例为肉瘤,2例为小细胞癌,1例为鳞癌,1例为黏液腺癌。切缘阳性10例(28.6%),侵犯精囊9例(25.71%),淋巴结阳性13例(37.14%)。TNM分期:T期6例,T期10例,T期7例,T期12例。危险度分级:低危患者5例(14.28%),中危9例(25.71%),高危21例(60%)。Gleason评分7分以下为6例(20.69%),7分为9例(31.03%),7分以上为14例(48.28%)。随访时间13~72月,术后密切监测PSA水平,术后生化复发共13例(37.14%),21例患者死亡,16例为前列腺特异性死亡。术后1、2、3年的生存率分别为:97.14%,88.57%,77.14%。结论:PSA正常的前列腺癌因无明显的临床就诊特征,精囊侵犯检出率高、Gleason评分及危险程度均偏高,3年生存率仅为77.14%。对于此类患者,不应以惯性思维认为PSA水平低,临床风险小,应更积极的完善检查,调整治疗策略,给此类患者带来更多的生存获益。     

Postoperative radiotherapy in 423 patients with pT3N0 prostate cancer

PURPOSE: To evaluate the treatment outcome in pT3N0 patients with adenocarcinoma of the prostate treated with an elective course of postoperative irradiation (RT). METHODS AND MATERIALS: During a 22-year period, a total of 423 pT3N0 prostate cancer patients were treated at a single medical center with prostatic fossa RT, which was the only adjuvant therapy given. The patient characteristics were as follows: median age 66 years; Stage pT3aN0 in 296 (70%) and pT3bN0 in 127 (30%); Gleason score 2-4 in 12 (2.8%), 5-6 in 157 (37.1%), 7 in 151 (35.7%), and 8-10 in 100 (23.6%); and the median and mean preoperative prostate-specific antigen (PSA) level was 10 and 15.9 ng/mL, respectively. Radiotherapy consisted of a median dose of 48 Gy delivered to the prostatic fossa and its immediate vicinity. The median follow-up was 7 years. RESULTS: The 5- and 10-year actuarial survival rate was 92% and 73%, respectively, and the 5- and 10-year disease-free survival rate (PSA <0.05 ng/mL) was 69% and 51%, respectively. In multivariate analysis, the Gleason score was the most important predictor for survival (p = 0.00005), and pathologic stage and Gleason score were independently predictive of disease-free survival (p = 0.00007 and 0.0003, respectively). The worst prognostic category was represented by pT3bN0, Gleason score 7-10 patients who had a 5.3 times greater risk of tumor recurrence than those with pT3aN0, Gleason score 2-6. A high (>25 ng/mL) preoperative PSA level was also a predictor of tumor recurrence (p = 0.03). A total of 43 patients (10.2%) developed clinical recurrence. This included 30 patients (7%) with distant metastases alone and 13 (3%) with local recurrence, which included 2 patients who also had distant disease. An additional 88 patients (20%) had PSA elevation (>0.05 ng/mL). This treatment program was well tolerated, with acute toxicity common (62%) but of no clinical significance. No late or severe toxicity was recorded. CONCLUSION: Adjuvant radiotherapy, as given in this study, appears to substantially reduce the expected incidence of local tumor recurrence in pT3N0 prostate cancer patients. The treatment outcome was poor in pT3bN0 and Gleason score 7-10 patients, with >80% showing evidence of clinical or PSA recurrence at 10 years after therapy. This group should be the target of a prospective trial of systemic therapy.     

以尿潴留为首发表现的前列腺癌临床分析（附43例）

目的:回顾分析以尿潴留为首发表现的前列腺癌患者的临床特点。方法:收集我院2001年7月至2014年7月以尿潴留为首发症状的前列腺癌患者43例,均经前列腺穿刺活检确诊。3例患者接受腹腔镜下腹膜外前列腺癌根治术,其余40例患者均接受经尿道前列腺电切术（transurethral resection of prostate,TURP）联合内分泌治疗［（最大限度雄激素阻断（maximal androgen blockade,MAB）］。统计其年龄分布、前列腺特异性抗原（prostate specific antigen,PSA）、直肠指检(digital rectal examination,DRE)阳性率、经直肠前列腺穿刺阳性针数、Gleason评分、骨转移、肿瘤分期、治疗后排尿恢复情况、IPSS评分及1年、3年、5年生存率。结果:43例患者的年龄中位数为69岁;直肠指检阳性率达81.4%（35/43）;PSA＞20 ng/ml者占62.8%（27/43）;经直肠前列腺穿刺（12+X针穿刺法）超过7针以上阳性的占76.7%（33/43）;Gleason评分≥7分占95.3%（41/43）;骨转移患者占76.7%（33/43）;临床分期T3b-T4期占88.4%（38/43）;治疗后6个月全部患者恢复了自主排尿,1年生存率为97.7%,3年生存率为79.1%,5年生存率为55.8%。结论:老年男性发生尿潴留应当考虑有前列腺癌的可能性,该类前列腺癌患者病程往往多为晚期且为高危患者,肿瘤压迫侵犯尿道及膀胱颈是排尿困难的主要原因,经尿道前列腺电切术联合内分泌治疗,可有效解除下尿路梗阻,控制肿瘤进展,提高患者生活质量。     

Dynamic contrast-enhanced magnetic resonance imaging of radiation therapy-induced microcirculation changes in rectal cancer

PURPOSE: To examine the impact of various patient, disease, and treatment characteristics on outcome in patients treated with neoadjuvant hormone therapy (NAHT) and external-beam radiation therapy (EBRT) for clinically localized, high-risk prostate adenocarcinoma (initial prostate-specific antigen [PSA] level >20, Gleason score 8-10 or Stage > or = T3). METHODS AND MATERIALS: A retrospective chart review was conducted on 407 patients treated between 1991 and 2001 with NAHT and EBRT for high-risk prostate cancer. The effect of tumor (PSA level, Gleason score, and T stage) and treatment (NAHT duration, total-hormone duration, preradiation PSA) characteristics on rates of biochemical disease-free survival (bDFS), prostate cancer-specific survival, and overall survival were examined. RESULTS: Median follow-up time was 78 months (range: 5-140 months). Actuarial bDFS at 5 years was 52% (95% confidence interval [CI], 46% to 57%) for the entire group. On multivariate analysis, initial PSA level (p = 0.004), Gleason score (p = 0.005), and preradiation PSA level (p < 0.001) were predictive of bDFS, whereas age, T stage, duration of NAHT, and duration of total hormone therapy were not predictive of outcomes. Gleason score and preradiation PSA level were also predictive of prostate cancer-specific survival rates. CONCLUSION: Improved bDFS in patients with high-risk prostate cancer was associated with lower initial PSA level, lower Gleason score, and lower preradiation PSA level. The duration of NAHT did not have an impact on outcomes, but the preradiation PSA was an important predictor of bDFS in high-risk patients.     

Histological diagnosis of prostate cancer in Korean men aged 70-79 years

BACKGROUND: The objective of this study was to evaluate the value of the prostate-specific antigen (PSA) in the diagnosis of prostate cancer in elderly Korean men, aged 70-79 years. METHODS: Patients with an abnormal digital rectal examination (DRE) and/or a serum PSA level greater than 2.0 ng/ml underwent a biopsy. A total of 344 men (median age 73 years) constituted the study cohort. RESULTS: Of 344 men, 163 (47.4%) were diagnosed with prostate cancer upon initial biopsy. The positive predictive value (PPV) for cancer was 48.4% for a PSA cutoff of 4 ng/ml, 65.3% for a cutoff of 10 ng/ml, and 87.0% for a cutoff of 20 ng/ml. When combined with an abnormal DRE, the predictive values for these PSA cutoffs increased to 79.3, 87.3 and 100%, respectively. When 10 ng/ml was chosen as a PSA cutoff level, about 50% of patients were found to have a Gleason score of 7 or higher. When 4 ng/ml was chosen as a PSA cutoff level, more than 50% of patients with an abnormal DRE were found to have a Gleason score of 7 or higher. CONCLUSIONS: In elderly men, more than 50% of patients are found to have cancers with a Gleason score of 7 or higher when their PSA level is greater than 10 ng/ml. This threshold may be lowered to 4 ng/ml in the presence of an abnormal DRE. Our findings provide a rationale for recommending a prostate biopsy in elderly patients with an abnormal DRE and/or an elevated serum PSA level. However, at present, it is not clear whether elderly men have better outcomes when they undergo cancer screening.     

河北医科大学第四医院前列腺癌患者的基线特征与生存分析

背景与目的：近年来，前列腺癌发病率逐年增高，但前列腺癌筛查工作仍不全面，国内前列腺癌数据库也相对匮乏。分析河北医科大学第四医院前列腺癌患者的基线特征、治疗以及生存情况等数据，为河北及周边地区前列腺癌的诊治提供参考。方法：回顾性分析2008年1月—2018年12月在河北医科大学第四医院泌尿外科就诊的857例前列腺癌患者信息，分析初次就诊时非转移性（M ₀ ）和转移性（M ₁ ）前列腺癌患者的基线特征、治疗方案和生存情况。对随访数据采用Kaplan-Meier法绘制生存曲线，并用log-rank检验比较两组之间生存率差异。结果：纳入基线统计的患者共计857例，中位年龄71岁，797例存在前列腺特异性抗原（prostate-specific antigen，PSA）记录，689例存在Gleason评分记录。412例M ₀ 患者和445例M ₁ 患者中，PSA≥100 ng/mL的患者分别占11.1%（44/397）和57.3%（229/400），Gleason评分≥8分的患者分别占46.9%（166/354）和63.9%（214/335）。纳入随访分析的患者共计606例，患者生存395例，死亡211例，其中182例死于肿瘤进展。M ₀ 和M ₁ 患者5年生存率分别为63.2%（76/120）和41.3%（102/247），M ₀ 和M ₁ 患者的中位生存期分别为85和 47个月（P＜0.01）。此外，在所有采用传统内分泌治疗［雄激素剥夺治疗（androgen deprivation therapy，ADT）或联合雄激素阻断治疗（combined androgen blockade，CAB）］的M ₁ 患者和高危转移性激素敏感性前列腺癌（metastatic hormone-sensitive prostate cancer，mHSPC）患者中，中位PSA进展时间（time to PSA progression，TTPP）分别为18和17个月。内分泌治疗初诊M ₀ 患者的中位TTPP为25个月。12例影像学检测未发现远处转移的去势抵抗性前列腺癌（non-metastatic castrate-resistant prostate cancer，NM-CRPC）患者，中位无转移生存期（metastasis-free survival，MFS）仅为16个月。结论：前列腺癌患者的年龄、PSA及Gleason评分偏高，多数患者在治疗时有转移，5年生存率偏低，因此应重视和加强前列腺癌的筛查工作。在接受内分泌治疗的M ₁ 患者进展为转移性去势抵抗性前列腺癌（metastatic castrate-resistant prostate cancer，mCRPC）的时间较短，此外，接受内分泌治疗的M ₀ 患者进展至NM-CRPC后，进展为mCRPC或死亡的时间也非常短，未来对于M ₁ 和NM-CRPC患者应采取更为积极的治疗，以延缓病情进展到mCRPC阶段。     

Five-year biochemical outcome and toxicity with transperineal CT-planned permanent I-125 prostate implantation for patients with localized prostate cancer

Purpose: To report the 5-year prostate-specific antigen (PSA) relapse-free survival outcome and incidence of long-term morbidity for patients with localized prostate cancer treated with CT-planned permanent I-125 prostate implantation using a transperineal technique (TPI).

Methods and Materials: Between 1989–1996, 248 patients with clinically localized prostate cancer were treated with TPI. The median age was 65 years (range: 45–80 years). The clinical stage was T1c in 143 patients (58%), Stage T2a in 102 (41%), and T2b in 3 (1%). Thirty patients (12%) had Gleason scores <6, 158 patients (64%) had Gleason scores of 6, and 60 (24%) had scores ≥7. The median pretreatment PSA was 7 ng/mL (range: 1–58 ng/mL). The median prescribed implant dose was 150 Gy. Patients were characterized as having favorable risk disease if their pretreatment PSA level was ≤10.0 ng/mL and Gleason score ≤6; those with one and two adverse prognostic features (PSA > 10 ng/mL and Gleason score >6) were classified as having intermediate and unfavorable risk disease, respectively. PSA relapse was defined according to the American Society of Therapeutic Radiation Oncology Consensus Statement, and toxicity was scored according to the Radiation Therapy Oncology Group morbidity scoring scale. The median follow-up was 48 months (range: 12–126 months).

Results: Thirty-eight patients (15%) developed a PSA relapse, and the overall 5-year PSA relapse-free survival (PRFS) rate was 71%. The 5-year PRFS rates for favorable-risk (n = 146), intermediate-risk (n = 85), and unfavorable-risk (n = 17) patients were 88%, 77%, and 38%, respectively (p < 0.0001). The 5-year PRFS rates among patients treated with a 2-month course of neoadjuvant androgen deprivation (NAAD) prior to TPI compared to patients treated with TPI only were 100% and 77%, respectively (p = 0.03). Multivariate analysis identified pretreatment PSA > 10 ng/mL and Gleason score >6 as independent predictors for biochemical relapse after TPI. The 5-year actuarial likelihood of late Grade 2 urinary toxicity was 41%. The 5-year likelihood of urethral stricture development was 10%, and the median time to stricture development was 18 months. One patient (0.4%) in the early phase of this clinical experience developed a Grade 4 urethral complication. The actuarial incidence of late Grade 2 rectal bleeding was 9%. One patient (0.4%) developed a Grade 4 rectal complication.

Conclusions: Especially for favorable risk disease, the 5-year biochemical outcome with this approach was excellent and appears to be comparable to other therapeutic interventions. Grade 2 urinary symptoms were common in these patients but gradually resolved in most. Improved treatment planning approaches that further constrain the urethral dose without compromising the target volume dose will likely decrease the incidence of Grade 2 and 3 urinary symptoms after TPI.     

Importance of margin extent as a predictor of outcome after adjuvant radiotherapy for Gleason score 7 pT3N0 prostate cancer

PURPOSE: To evaluate, in Gleason score 7, pT3N0 prostate cancer patients with positive surgical margins, the predictors of progression-free survival and to identify a patient subgroup that would benefit from immediate adjuvant postoperative radiotherapy (ART). METHODS AND MATERIALS: Between November 1989 and August 1998, 76 men underwent radical prostatectomy and were found to have capsular penetration (pT3N0), surgical Gleason score 7, tumor present at the resection margin, and an undetectable postoperative prostate-specific antigen (PSA) level. All surgical specimens underwent whole-mount serial sectioning to determine the degree of margin positivity (focal vs. extensive). Of the 76 men, 45 underwent early ART (within 6 months with a median dose of 64.8 Gy), and 31 had no immediate treatment. We defined freedom from PSA failure (bNED) as the absence of two consecutive PSA rises >0.2 ng/mL. RESULTS: The median follow-up time was 5.1 years (range, 2-10 years). The ART and non-ART patients were similar with respect to preoperative PSA level, Gleason score (4 + 3 vs. 3 + 4), presence of seminal vesicle invasion, and margin extent. On univariate analysis, margin extent was predictive for improved bNED (5-year bNED rate of 92% vs. 58%, p = 0.010, for men with focal and extensive margins, respectively). Gleason score (4 + 3 vs. 3 + 4), seminal vesicle invasion, and ART were not statistically significant predictors. On multivariate analysis, the preoperative PSA level, margin extent, and ART were independent significant factors. In the group with extensive surgical margins, men receiving ART had a significantly greater 5-year bNED survival rate compared with the non-ART patients (73% vs. 31%, p = 0.004). CONCLUSION: These data suggest that the amount of microscopic residual tumor significantly affects bNED after radical prostatectomy for Gleason score 7, pT3N0 prostate cancer. In addition, men with pathologic evidence of microscopic local disease appear to benefit from early ART compared with untreated controls.     

Combined modality treatment in the management of high-risk prostate cancer

PURPOSE: The efficacy of a multimodality protocol using neoadjuvant and concomitant hormonal therapy, brachytherapy, and three-dimensional conformal external beam radiotherapy (RT) in high-risk prostate cancer was evaluated using biochemical outcomes and posttreatment biopsy results. METHODS AND MATERIALS: Between February 1994 and November 1999, 132 high-risk patients were treated with combined hormonal therapy (9 months), permanent radioactive seed brachytherapy, and external beam RT, with follow-up ranging from 36 to 88 months (median, 50 months). The eligibility criteria were any of the following: Gleason score 8-10, initial prostate-specific antigen (PSA) level >20 ng/mL, clinical Stage T2c-T3, or positive seminal vesicle biopsy, or two or more of the following: Gleason score 7, PSA level >10-20 ng/mL, or Stage T2b. Twenty percent of patients had a positive seminal vesicle biopsy before therapy. Negative laparoscopic pelvic lymph node dissections were performed in 44% of patients. RESULTS: The actuarial overall freedom from PSA failure rate was 86% at 5 years. The freedom from PSA failure rate at 5 years was 97% for those with a Gleason score of < or =6 (35 of 36), 85% for a Gleason score of 7 (50 of 59), and 76% for a Gleason score of 8-10 (28 of 37; p = 0.03). A trend was noted toward worse outcomes in seminal vesicle biopsy-positive patients, with a 5-year freedom from PSA failure rate of 74% vs. 89% for all other patients (p = 0.06). Posttreatment prostate biopsies were performed in 47 patients and were negative in 96% at the first biopsy and 100% at the last biopsy. CONCLUSION: Trimodality therapy with androgen suppression, brachytherapy, and external beam RT for high-risk prostate cancer results in excellent biochemical and pathologically confirmed local control.     

Prognostic significance of race on biochemical control in patients with localized prostate cancer treated with permanent brachytherapy: multivariate and matched-pair analyses

PURPOSE: To compare PSA relapse-free survival (PSA-RFS) between African-American (AA) and white American (WA) males treated with permanent prostate brachytherapy (PPB) for clinically localized prostate cancer. METHODS AND MATERIALS: One thousand eighty-one consecutive patients, including 246 African-Americans, underwent PPB with 103Pd or 125I, alone or with external beam radiation therapy between September 1992 and September 1999. Computer-generated matching was performed to create two identical cohorts of WA and AA males, based on the use of neoadjuvant androgen ablation (NAAD), pretreatment PSA, and Gleason score. Presenting characteristics were used to define risk groups, as follows: Low risk had PSA 10 or Gleason score >or=7, and high risk had PSA >10 and Gleason score >or=7. PSA-RFS was calculated using the Kattan modification of the ASTRO definition, and the log-rank test was used to compare Kaplan-Meier PSA-RFS curves. Univariate and multivariate analyses were performed to determine predictors of PSA-RFS. RESULTS: Overall, univariate analysis revealed that AA males at presentation had lower disease stage (p = 0.01), had lower Gleason scores (p = 0.017), were younger (p = 0.001), and were more likely to receive NAAD (p = 0.001) than their WA counterparts. There were no differences in pretreatment PSA, isotope selection, use of external beam radiation therapy, median follow-up, or risk group classification between AA and WA males. Pretreatment PSA and Gleason score were significant predictors of PSA-RFS in multivariate analysis, and race was not significant. There was no significant difference between the 5-year PSA-RFS for AA males (84.0%) and the matched cohort of WA males (81.2%) (p = 0.384). Race was not a predictor of 5-year PSA-RFS among patients treated with or without NAAD and within low-, intermediate-, and high-risk groups. CONCLUSION: Race is not an independent predictor of 5-year PSA-RFS in patients with localized prostate cancer treated with PPB. This result is consistent with other studies that also show that race does not contribute to differences in outcome after definitive therapies for localized prostate cancer.     

The clinical utility of the percent of positive prostate biopsies in predicting biochemical outcome following external-beam radiation therapy for patients with clinically localized prostate cancer

PURPOSE: An investigation was performed of the clinical utility of the percent of positive prostate biopsies in predicting prostate-specific antigen (PSA) outcome following external-beam radiation therapy (RT) for men with PSA-detected or clinically palpable prostate cancer. METHODS AND MATERIALS: A Cox regression multivariable analysis was used to determine whether the percent of positive prostate biopsies provided clinically relevant information about PSA outcome following external beam RT in 473 men while accounting for the previously established risk groups based on the pretreatment PSA level, biopsy Gleason score, and the 1992 American Joint Commission on Cancer (AJCC) clinical T stage. RESULTS: Controlling for the known prognostic factors, the percent of positive prostate biopsies added clinically significant information (p = 0.02) regarding time to PSA failure following RT. Specifically, 76% of the patients in the intermediate risk group (1992 AJCC T(2b) or biopsy Gleason 7 or PSA > 10 ng/mL and < or = 20 ng/mL) could be classified into either an 30% or 85% 5-year PSA control cohort using the preoperative prostate biopsy data. CONCLUSION: The previously validated stratification of PSA outcome following radical prostatectomy (RP) using the percent of positive prostate biopsies in intermediate-risk patients is also clinically significant for men treated with external beam RT. The percent positive prostate biopsies should be considered in conjunction with the PSA level, biopsy Gleason score, and 1992 AJCC clinical T stage when counseling patients with newly diagnosed and clinically localized prostate cancer about PSA outcome following RP or external beam RT.     

Role of hormonal therapy in the management of intermediate- to high-risk prostate cancer treated with permanent radioactive seed implantation

PURPOSE: To study the impact of hormonal therapy (HTx) on intermediate- to high-risk prostate cancer treated with permanent radioactive seed implantation. METHODS AND MATERIALS: Patients with Stage T1b-T3bN0 prostate cancer, and Gleason score > or = 7 or prostate-specific antigen (PSA) level >10 ng/mL were treated with seed implantation with or without HTx. Their disease was defined as intermediate risk (PSA 10-20, Gleason score 7, or Stage T2b) or high risk (two or more intermediate criteria, or PSA >20 ng/mL, Gleason score 8-10, or Stage T2c-T3). The median follow-up for 201 eligible patients was 42 months (range 18-110). Biochemical failure was defined as a rising PSA >1.0 ng/mL. Pretreatment disease characteristics, implant dose, and HTx were evaluated using univariate and multivariate analyses. RESULTS: HTx significantly improved 5-year actuarial freedom from biochemical failure rate, 79% vs. 54% without HTx. In addition, high-dose, PSA < or = 15 ng/mL, intermediate risk, and Stage T2a or lower significantly improved outcome in the univariate analyses. HTx was the most significant predictor of 5-year actuarial freedom from biochemical failure (p <0.0001) in a multivariate analysis. The best outcome was in the intermediate-risk patients treated with a high implant dose and HTx, resulting in a 4-year actuarial freedom from biochemical failure rate of 94%. CONCLUSION: In this retrospective review, HTx improved outcome in intermediate- to high-risk prostate cancer patients treated with brachytherapy. HTx was the most important prognostic factor in the univariate and multivariate analyses.     

Outcome predictors for the increasing PSA state after definitive external-beam radiotherapy for prostate cancer.

PURPOSE: To identify predictors of distant metastases (DM) among patients who develop an isolated prostate-specific antigen (PSA) relapse after definitive external-beam radiotherapy for clinically localized prostate cancer. MATERIALS AND METHODS: A total of 1,650 patients with clinical stage T1 to T3 prostate cancer were treated with high-dose three-dimensional conformal radiotherapy. Of these, 381 patients subsequently developed three consecutive increasing PSA values and were characterized as having a biochemical relapse. The median follow-up time was 92 months from the completion of radiotherapy. RESULTS: The 5-year incidence of DM after an established PSA relapse was 29%. In a multivariate analysis, PSA doubling time (PSA-DT; P < .001), the clinical T stage (P < .001), and Gleason score (P = .007) were independent variables predicting for DM after established biochemical failure. The PSA-DT for favorable-, intermediate-, and unfavorable-risk patients who developed a biochemical failure was 20.0, 13.2, and 8.2 months, respectively (P < .001). The 3-year incidence of DM for patients with PSA-DT of 0 to 3, 3 to 6, 6 to 12, and more than 12 months was 49%, 41%, 20%, and 7%, respectively (P < .001). Patients with PSA-DT of 0 to 3 and 3 to 6 months demonstrated a 7.0 and 6.6 increased hazard of developing DM or death, respectively, compared with patients with a DT more than 12 months. CONCLUSION: In addition to clinical stage and Gleason score, PSA-DT was a powerful predictor of DM among patients who develop an isolated PSA relapse after external-beam radiotherapy for prostate cancer. Patients who develop biochemical relapse with PSA-DT < or = 6 months should be considered for systemic therapy or experimental protocols because of the high propensity for rapid DM development.     

Matched-pair analysis of conformal high-dose-rate brachytherapy boost versus external-beam radiation therapy alone for locally advanced prostate cancer.

PURPOSE: We performed a matched-pair analysis to compare our institution's experience in treating locally advanced prostate cancer with external-beam radiation therapy (EBRT) alone to EBRT in combination with conformal interstitial high-dose-rate (HDR) brachytherapy boosts (EBRT + HDR). MATERIALS AND METHODS: From 1991 to 1998, 161 patients with locally advanced prostate cancer were prospectively treated with EBRT + HDR at William Beaumont Hospital, Royal Oak, Michigan. Patients with any of the following characteristics were eligible for study entry: pretreatment prostate-specific antigen (PSA) level of >/= 10.0 ng/mL, Gleason score >/= 7, or clinical stage T2b to T3c. Pelvic EBRT (46.0 Gy) was supplemented with three (1991 through 1995) or two (1995 through 1998) ultrasound-guided transperineal interstitial iridium-192 HDR implants. The brachytherapy dose was escalated from 5.50 to 10.50 Gy per implant. Each of the 161 EBRT + HDR patients was randomly matched with a unique EBRT-alone patient. Patients were matched according to PSA level, Gleason score, T stage, and follow-up duration. The median PSA follow-up was 2.5 years for both EBRT + HDR and EBRT alone. RESULTS: EBRT + HDR patients demonstrated significantly lower PSA nadir levels (median, 0.4 ng/mL) compared with those receiving EBRT alone (median, 1.1 ng/mL). The 5-year biochemical control rates for EBRT + HDR versus EBRT-alone patients were 67% versus 44%, respectively (P <.001). On multivariate analyses, pretreatment PSA, Gleason score, T stage, and the use of EBRT alone were significantly associated with biochemical failure. Those patients in both treatment groups who experienced biochemical failure had a lower 5-year cause-specific survival rate than patients who were biochemically controlled (84% v 100%; P <.001). CONCLUSION: Locally advanced prostate cancer patients treated with EBRT + HDR demonstrate improved biochemical control compared with those who are treated with conventional doses of EBRT alone.     

Primary Gleason pattern does not impact survival after permanent interstitial brachytherapy for Gleason score 7 prostate cancer

BACKGROUND: The impact of primary Gleason pattern was determined on cause-specific (CSS), biochemical progression-free (bPFS), and overall survival (OS) after brachytherapy for Gleason score 7 prostate cancer. METHODS: From April 1995 to October 2003, 530 patients underwent brachytherapy for Gleason score 3+4 (n = 300) or Gleason 4+3 (n = 230) prostate cancer. All patients underwent brachytherapy more than 3 years before analysis. The median follow-up was 5.7 years. Of the 530 patients, 412 (77.7%) received supplemental external beam radiation therapy (XRT) and 177 (33.4%) received androgen deprivation therapy. bPFS was defined by a prostate-specific antigen (PSA) 相似文献   

Predictors of mortality after androgen-deprivation therapy in patients with rapidly rising prostate-specific antigen levels after local therapy for prostate cancer

BACKGROUND: The authors identified biochemical and pathologic factors that were associated significantly with prostate cancer-specific mortality (PCSM) after androgen deprivation therapy (ADT) in men who had rapidly rising prostate-specific antigen (PSA) levels after they received local treatment. METHODS: The study population consisted of 67 patients who had a PSA doubling time (DT) < or =6 months after radical prostatectomy (n = 50 patients) or external beam radiation therapy (n = 17 patients) for localized prostate cancer. Multivariate Cox proportional hazards regression analysis was used to evaluate whether the interval to PSA failure, pre-ADT PSA DT, PSA level at the time of ADT initiation, time to PSA nadir, PSA nadir after 8 months on ADT, and Gleason score were associated significantly with the time to PCSM 8 months after the initiation of ADT. RESULTS.: A PSA nadir >0.2 ng/mL (adjusted hazard ratio [HR], 8.0; 95% confidence interval [95% CI], 1.7-38.7; P = 0.009) and a Gleason score > or =8 (adjusted HR, 5.2; 95% CI, 1.3-20.6; P = 0.02) were associated significantly with a short time to PCSM. The cumulative incidence estimates of 3-year PCSM were 5.8% versus 50.9% for patients with a PSA nadir < or =0.2 ng/mL versus >0.2 ng/mL, respectively, and 10.8% versus 35.8% for patients who had tumors with a Gleason score < or =7 versus > or =8, respectively. CONCLUSIONS.: Among men with a PSA DT < or =6 months, both a PSA nadir >0.2 ng/mL after ADT and a Gleason score > or =8 cancer identified men who were at high risk for PCSM. These men would be ideal candidates for Phase III studies that evaluate the impact on survival of new systemic therapies for prostate cancer.     

Permanent interstitial brachytherapy for clinically organ-confined high-grade prostate cancer with a pretreatment PSA < 20 ng/mL

The objective of this study was to determine the effect of biopsy Gleason score 8 and 9 histology on biochemical outcome following a permanent prostate brachytherapy approach that includes multiple periprostatic seeds and supplemental external beam radiation. Forty-six consecutive T1c-T2b (1997 AJCC) patients with Gleason score 8 and 9 prostate cancer who were either hormone naive (33 patients) or received cytoreductive (< or =6 months) hormonal therapy (13 patients) underwent brachytherapy from June 1995 to November 2000. The median patient age was 69.7 years, with a median pretreatment prostate-specific antigen (PSA) of 7.7 ng/mL. The median follow-up was 58 months (range 27-93 months). Forty-five of the patients were implanted with Pd-103 and 44 received supplemental external beam radiation therapy (45 Gy). Biochemical success was defined by either a PSA < or = 0.4 ng/mL after a nadir or by the ASTRO consensus definition. The actuarial 7-year biochemical disease-free survival was 84.8% using either a PSA < or = 0.4 ng/mL or the ASTRO consensus definition. The median postimplant PSA was less than 0.1 ng/mL for both the hormone naive and hormonally manipulated patients. The utilization of hormonal therapy for 6 months or less duration resulted in a statistically nonsignificant improvement in biochemical outcome (92.3% versus 81.8%, P = 0.393). When stratified by pretreatment PSA, 87.9% of patients with a pretreatment PSA < or = 10 ng/mL and 76.9% with a pretreatment PSA > 10 ng/mL (P = 0.377) remained biochemically free of disease. In multivariate analysis, none of the clinical, treatment, or dosimetric parameters predicted for outcome. Following a permanent prostate brachytherapy approach that used multiple periprostatic seeds, the majority of patients with clinically organ-confined Gleason score 8 and 9 prostate cancer remain biochemically free of disease with identical outcomes for both biochemical definitions of success.     

Prostate-specific antigen velocity and prostate cancer gleason grade and stage

BACKGROUND: Increased preoperative prostate-specific antigen (PSA) velocity (PSAV) has been associated with increased prostate cancer mortality and higher Gleason scores. The authors evaluated the relation between PSAV, biopsy Gleason score, and pathologic stage in men who were enrolled in a prostate cancer screening trial. METHODS: Data were analyzed from 1441 men who were enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who received > or =2 PSA screens and were diagnosed with prostate cancer within 1 year of the last screen. PSAV was estimated by using all screening PSA values within 6 years prediagnosis. RESULTS: Both PSA and PSAV were related to biopsy Gleason score. The multivariable odds ratios (OR), controlling for PSA and demographics, for having a Gleason score of 7 to 10 were 1.3 (95% confidence interval [95% CI], 0.9-1.9), 2.2 (95% CI, 1.5-3.3), and 2.3 (95% CI, 1.4-3.9) for men with PSAV values from 0.5 to 1 ng/mL per year, from 1 to 2 ng/mL per year, and >2 ng/mL per year, respectively, compared with men who had PSAV values <0.5 ng/mL per year. The median PSAV was 0.60 ng/mL per year for men with Gleason scores from 2 to 6 versus 0.84 ng/mL per year for men with Gleason scores from 7 to 10 (P < .0001). Among 658 men who underwent prostatectomy, both PSA and PSAV were associated with advanced pathologic stage in univariate analyses; however, when the analysis controlled for clinical stage and biopsy Gleason score, the associations of PSA and PSAV were no longer statistically significant. CONCLUSIONS: PSAV and PSA levels were associated independently with biopsy Gleason score. Among men who underwent prostatectomy, PSAV and PSA were not predictive of advanced pathologic stage when the analysis was controlled for biopsy Gleason score and clinical stage. It cannot be determined yet whether PSAV is predictive of long-term prostate cancer outcome in this cohort.     

A comparison of external beam radiation therapy versus radical prostatectomy for patients with low risk prostate carcinoma diagnosed, staged, and treated at a single institution

BACKGROUND: The authors retrospectively reviewed their institution's long term experience treating a group of comparably staged low risk prostate carcinoma patients with either radical prostatectomy or external beam radiation therapy (RT) to determine whether the method of treatment resulted in significant differences in biochemical control and/or survival. METHODS: From January of 1987 through December of 1994, 382 patients (157 who underwent radical prostatectomy and 225 who received external beam RT) were treated with curative intent for localized prostate carcinoma at William Beaumont Hospital. All patients had a pretreatment serum prostate specific antigen (PSA) level < or =10.0 ng/mL and a biopsy Gleason score or =0.2 ng/mL at any time after prostatectomy. For RT patients, biochemical failure was defined according to the American Society for Therapeutic Radiology and Oncology Consensus Panel definition. Pretreatment PSA levels and Gleason scores were not significantly different between patients treated with radical prostatectomy or RT. The median follow-up in each treatment group was 5.5 years. RESULTS: The 7-year actuarial rates of biochemical control and cause specific survival were not significantly different between patients treated either with radical prostatectomy or RT (67% vs. 69% for biochemical control and 99% vs. 97% for cause specific survival, respectively). A number of clinical, pathologic, and treatment-related factors were analyzed for an association with biochemical failure (i.e., age, pretreatment PSA, Gleason score, and treatment modality). Only pretreatment PSA and Gleason score were significantly related to outcome in both univariate and multivariate analyses. CONCLUSIONS: Low risk prostate carcinoma patients with similar pretreatment PSA levels and biopsy Gleason scores treated at the same institution with either radical prostatectomy or RT achieved similar 7-year rates of biochemical control and cause specific survival, regardless of treatment technique. These findings suggest that for patients with pretreatment PSA levels 相似文献   

The impact of the biopsy Gleason score on PSA outcome for prostate cancer patients with PSA < or = 10 ng/ml and T1c,2a: implications for patient selection for prostate-only therapy

PURPOSE: This study was performed to determine the ability of the biopsy Gleason score, prostate-specific antigen (PSA) level, and the 1992 American Joint Commission on Cancer (AJCC) clinical T-stage for predicting time to postoperative PSA failure for patients with a PSA < or =10 ng/ml and T1c or T2a disease. Specific attention is given to the patient subgroup with biopsy Gleason 3 + 4 vs. 4 + 3. METHODS AND MATERIALS: A concordance map of the biopsy and prostatectomy Gleason grades and a clinical-pathologic correlation of the PSA, biopsy Gleason score, and 1992 AJCC T-stage and pathologic stage were performed. A Cox regression multivariable analysis was used to evaluate the ability of the biopsy Gleason score, PSA, and 1992 AJCC T-stage to predict time to PSA failure for 457 men managed with a radical prostatectomy (RP). RESULTS: The absence of prostatectomy Gleason grade 4 or 5 disease was noted in 71%, 50%, and 11% of patients with biopsy Gleason score 2-6, 3 + 4, and > or =4 + 3 disease respectively while pathologic evidence of seminal vesicle invasion was noted in 2%, 4%, and 17% of these patients respectively. Estimates of 5-year PSA failure-free survival rates were not statistically different for patients with biopsy Gleason score 2-6 vs. 3 + 4 (79% vs. 81%; p = 0.93), but were significantly different for patients having biopsy Gleason score 2-6 vs. 4 + 3 (79% vs. 62%; p = 0.04) or 2-6 vs. 8-10 (79% vs. 18%; p = 0.0001) prostate cancer. CONCLUSION: Based on the pathologic stage and PSA control data following RP, patients with biopsy Gleason 3 + 4 disease and PSA < or =10 ng/ml and 1992 AJCC T1c or T2a disease may be suitable candidates for radiation therapy directed at the prostate only.