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.     

Prostate specific antigen outcome based on the extent of extracapsular extension and margin status in patients with seminal vesicle negative prostate carcinoma of Gleason score < or = 7

BACKGROUND: Early (< or = 2 years) prostate specific antigen (PSA) failure after radical prostatectomy (RP) has been shown to predict for distant failure. After excluding patients with the pathologic predictors of early PSA failure, an analysis of PSA failure free (bNED) survival was performed to identify patients who may benefit from the use of postprostatectomy radiation therapy (RT). METHODS: Of 1,028 patients treated with RP for clinically localized prostate carcinoma between 1989 and 1999, 862 (84%) had either organ confined (OC), specimen confined (SC), or margin positive disease with negative seminal vesicles (SV) and a prostatectomy Gleason score < or = 7. A Cox regression multivariate analysis was performed in these patients evaluating the ability of the extent of extracapsular extension (ECE) (into but not through the capsule, SC focal ECE, SC established ECE, margin positive) and prostatectomy Gleason score (2-6 vs. 7) to predict time to postoperative PSA failure. RESULTS: SC focal ECE (P = 0.0017), SC established ECE (P < 0.0001), and margin positive disease (P < 0.0001) were significant predictors of time to postoperative PSA failure, whereas prostatectomy Gleason score and disease extending into but not through the capsule were not. Five-year bNED rates were 90%, 88%, 69%, 45%, and 33% for patients with OC, into but not through capsule, SC focal ECE, SC established ECE, and margin positive prostate carcinoma, respectively. CONCLUSIONS: Patients with SC ECE or margin positive prostate carcinoma and a prostatectomy Gleason score < or = 7 with no evidence of SV invasion may benefit from adjuvant postoperative RT.     

Tumour growth fraction measured by immunohistochemical staining of Ki67 is an independent prognostic factor in preoperative prostate biopsies with small‐volume or low‐grade prostate cancer

Accurate prognostic parameters in prostate biopsies are needed to better counsel individual patients with prostate cancer. We evaluated the prognostic impact of morphologic and immunohistochemical parameters in preoperative prostate cancer biopsies. A consecutive series of prostate biopsies of 279 men (72% with clinical stage T1c and 23% with T2) who subsequently underwent radical prostatectomy was prospectively analysed for Gleason score, number and percentage of positive cores (NPC, PPC), total percentage of biopsy tissue with tumour (TPT), maximum tumour percentage per core (MTP), and expression of Ki67, Bcl‐2 and p53. All biopsy features were significantly associated with at least one feature of the radical prostatectomy specimen. pT stage was independently predicted by PSA, seminal vesicle invasion by Ki67 LI, positive margins by PSA and MTP, large tumour diameter by PSA and PPC, and Gleason score by biopsy Gleason score, MTP, and Ki67 LI, respectively. Biopsy Gleason score, NPC (1 vs. >1), TPT (<7 vs. ≥7%), and Ki67 LI (<10 vs. ≥10%) were significant predictors of biochemical recurrence after radical prostatectomy (p < 0.01, each). KI67 LI was the only independent prognostic factor in case of a low TPT (<7%) or low Gleason score (<7), the hazard ratio being 6.76 and 6.44, respectively. In summary, preoperative Gleason score, NPC, TPT and Ki67 LI significantly predict the risk of recurrence after radical prostatectomy, and Ki67 is an independent prognosticator in biopsies with low‐volume or low‐grade prostate cancer. Analysis of Ki67 LI in these biopsies may help to better identify patients with clinically insignificant prostate cancer. © 2008 Wiley‐Liss, Inc.     

Predicting prostate carcinoma volume and stage at radical prostatectomy by assessing needle biopsy specimens for percent surface area and cores positive for carcinoma, perineural invasion, Gleason score, DNA ploidy and proliferation, and preoperative serum prostate specific antigen: a report of 454 cases

BACKGROUND: DNA ploidy analysis of prostate carcinoma is a generally accepted prognostic marker, particularly when tumors are extraprostatic at the time of surgery. In the past decade, the DNA content of prostate carcinoma frequently has been assessed in needle biopsy specimens based on the assumption that ploidy, in conjunction with serum prostate specific antigen (PSA) and Gleason score, provides valuable pretreatment information. METHODS: Between 1995 and 1998, the authors identified a consecutive series of 454 prostate carcinomas, verified by needle biopsies and followed by radical retropubic prostatectomies (RRP). Based on the needle biopsies, DNA ploidy and MIB-I immunostaining were measured by digital image analysis (DIA). The authors also quantified the percent of nuclei in four categories from the DNA histograms. The DIA data were combined with the age of the patient at diagnosis, the serum PSA, Gleason score, percent cores and percent surface area positive for carcinoma, and status of perineural invasion in multivariate models using tumor volume and risk of extraprostatic extension (EPE) at RRP as the outcome variables. RESULTS: Joint predictors of tumor volume at RRP were the percent cores positive for carcinoma (P < 0.0001), serum PSA (P < 0.0001), the percent surface area positive for carcinoma (P < 0.0001), and the percent nuclei classified by DNA quantification to be in the "S-phase" category (P = 0.03). Joint predictors of risk of EPE were the percent cores positive for carcinoma (P = 0.0004), a Gleason score of 7 (P < 0.0001), a Gleason score of 8 or 9 (P < 0.0001), serum PSA (P = 0.006) and perineural invasion (P = 0.02). CONCLUSIONS: After adjusting for traditional prognostic markers, DNA ploidy interpretation and MIB-I quantitation of prostate carcinoma did not appear to jointly predict either outcome variable in the multivariate models. However, a quantitative measure related to both ploidy and proliferation, the percent of nuclei in the putative "S-phase" category from the DIA histograms, was found to jointly predict for tumor volume.     

Association between percentage of tumor involvement and Gleason score upgrading in low-risk prostate cancer

To find the predictors of Gleason score upgrading in a cohort of low-risk prostate cancer patients, data were analyzed comprising 1,632 consecutive men with low-risk prostate cancer who underwent radical prostatectomy between 1993 and 2009. Assessment focused on preoperative parameters including patient age, race, diagnostic prostate-specific antigen (PSA) levels, clinical stage and biopsy Gleason score, along with pathological parameters including percentage of tumor involvement (PTI), tumor laterality, pathological stage, extra-capsular extension, seminal vesicle invasion, and surgical margins. These parameters were analyzed using univariate and multivariate methods. Kaplan?CMeier curves compared differences in biochemical disease-free survival in men having cancers with and without Gleason score upgrading. Cases involving pathological Gleason score upgrading were identified in 723 (44.3?%) of 1,632 patients. Kaplan?CMeier PSA recurrence-free survival curves showed a difference in outcome between men with and without Gleason score upgrading (p?<?0.001). Of Gleason score upgraded patients, 35 (4.8?%) men had PTI of <5?%, 237 (32.8?%) had PTI of 5?C9.9?%, 177 (24.5?%) had PTI of 10?C14.9?%, and 274 (37.9?%) had PTI????15?% (p?<?0.001). PTI (p?<?0.001) along with diagnostic PSA, patient age, diagnostic biopsy Gleason score, pathologic stage, and surgical margin status were independent predictors of pathological Gleason score upgrading on multivariate logistic regression. PTI correlates closely with Gleason score upgrading in a low-risk prostate cancer cohort. Low-risk prostate cancer patients with clinical findings suggestive of high PTI or large volume cancers should not benefit from active surveillance strategies.     

Using PSA,biopsy Gleason score,clinical stage,and the percentage of positive biopsies to identify optimal candidates for prostate-only radiation therapy

PURPOSE: An identification of prostate cancer patients most likely to benefit from prostate-only radiation was made based upon the pretreatment prostate-specific antigen (PSA), biopsy Gleason score, clinical stage, percentage of positive biopsies, and the 5-year postoperative PSA outcome. METHODS: Between 1989 and 2000, 2099 patients underwent radical prostatectomy for clinically localized prostate cancer. The primary end points were pathologic evidence of seminal vesicle invasion 2(SVI), extracapsular extension (ECE) with or without positive surgical margins, and the 5-year postoperative PSA outcome. RESULTS: Pretreatment PSA, biopsy Gleason score, and clinical stage were used to assign patients to low-, intermediate-, and high-risk groups. These risk groups were stratified by the percentage of positive biopsies and the primary pathologic and biochemical outcomes examined. The rates of SVI, ECE with positive margin, and no biochemical evidence of disease (bNED) for low-risk patients with < or =50% positive biopsies were 2%, 7%, and 93%, respectively. Patients with >50% positive biopsies had higher rates of SVI and ECE (5% and 11%, respectively) and 52% bNED (p < 0.0001). For intermediate-risk patients with < or =17% positive biopsies, the rates of SVI, ECE with positive margin, and bNED were 3%, 9%, and 90%, respectively. As the percentage of positive biopsies increased above 17% in intermediate-risk patients, there was a statistically significant increase in SVI and ECE and a significant decrease in bNED. CONCLUSIONS: Low-risk patients with < or =50% positive biopsies and intermediate-risk patients with < or =17% positive biopsies had a very low risk of SVI and ECE with positive surgical margins. Given that the presence of SVI and ECE with positive surgical margins was uncommon (<10%) with a > or =90% PSA failure-free survival after radical prostatectomy, these patients may be optimal candidates for radiation therapy directed at the prostate only (prostate gland + 1.5-cm margin).     

Prognostic significance of preoperative factors in localized prostate carcinoma treated with radical prostatectomy: importance of percentage of biopsies that contain tumor and the presence of biopsy perineural invasion

BACKGROUND: Predicting outcome for men with clinically localized prostate carcinoma treated with curative intent remains imprecise and further evaluation of accepted and potential predictive factors is needed. METHODS: The authors studied 696 men with localized prostate carcinoma diagnosed on transrectal biopsy and treated with radical prostatectomy at one institution between 1986 and 1999 to determine the relation between putative pretreatment prognostic factors and disease-free survival. Clinical stage, Gleason score, perineural invasion, number of biopsies containing tumor, and serum prostate specific antigen (PSA) were evaluated as predictors of extracapsular extension, seminal vesicle involvement, lymph node metastases, and surgical margin involvement as well as outcome after surgery. Kaplan-Meier method and Cox regression analyses were used to evaluate the contribution of different factors to adverse pathologic features and relapse. RESULTS: At mean follow-up of 56.9 months (range, 1.0-177.9 months; median, 54.9 months), 26.1% (182 of 696 patients) of patients had developed a disease recurrence. Pretreatment serum PSA concentration, biopsy Gleason score, and clinical stage as well as number of biopsies involved with tumor as a percentage of the total number obtained were found to be independent predictors of outcome. In patients with PSA > 10 ng/mL, biopsy perineural invasion and percentage of biopsies containing tumor were found to independently predicted disease recurrent. Increased number of biopsies involved with tumor independently predicted extracapsular extension, margin involvement, seminal vesicle, and lymph node involvement. CONCLUSIONS: This study demonstrated that the proportion of prostate biopsy cores containing tumor is an independent predictor of outcome after subsequent radical prostatectomy and suggested that perineural invasion has a predictive role in patients with a preoperative PSA > 10 ng/ml.     

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.     

Cyclooxygenase-2 (COX-2) expression is an independent predictor of prostate cancer recurrence

Lack of reliable prognostic markers hinders accurate prediction of disease progression in prostate cancer. The inducible proinflammatory enzyme cyclooxygenase-2 (COX-2) is implicated in prostate carcinogenesis, but its role in cancer progression is less clear. We examined whether COX-2 expression evaluated by immunohistochemistry (IHC) in radical prostatectomy (RP) specimens can predict biochemical recurrence. Archival prostate cancer specimens (n = 60) were obtained from patients who underwent RP, but had not received neoadjuvant hormonal therapy. Twenty-three patients had biochemical or clinical recurrence (mean time of recurrence: 38.2 months), and 37 patients were recurrence free (mean follow-up: 95 months). COX-2 expression was determined by IHC, using an anti-COX-2 antibody. Three individuals scored the staining independently, as high- or low-expression. COX-2 was expressed in prostate cancer cells, in adjacent normal glands and in specimens from patients who later progressed. At 62-months follow-up, COX-2 staining predicted progression with 82.4% sensitivity and 81.3% specificity. Sensitivity (86.4%) and specificity (86.7%) improved at > or = 100-months follow-up. In univariate analysis, Gleason score, preoperative PSA, extraprostatic extension, margin, seminal vesicle invasion, and high COX-2 expression were significant predictors of biochemical recurrence (p < 0.05). In multivariate analysis, preoperative PSA (hazard ratio/unit PSA change 1.080; p = 0.0036) and COX-2 expression (hazard ratio 16.442; p < 0.0001) were independent prognostic indicators. Patients with PSA > 7 ng/ml and high COX-2 expression had the highest probability of recurrence (Kaplan-Meier analysis). COX-2 expression is an independent predictor of prostate cancer progression following RP and underscores the significance of inflammatory factors in this process.     

Utilizing predictions of early prostate-specific antigen failure to optimize patient selection for adjuvant systemic therapy trials.

PURPOSE: Prostate-specific antigen (PSA) failure within 2 years after radical prostatectomy (RP) has been shown to be a clinically significant predictor of distant failure. This study was performed to estimate 2-year PSA failure rates on the basis of readily available clinical and pathologic factors to identify patients for whom effective adjuvant systemic therapy is needed. PATIENTS AND METHODS: A Cox regression multivariable analysis was used to determine whether the percentage of positive prostate biopsies, PSA level, and the pathologic findings at RP in 1,728 men provided clinically relevant information about PSA outcome after RP. A bootstrapping technique with 2,000 replications was used to provide 95% confidence intervals for the predicted 2-year PSA failure rates, which were determined on the basis of the independent clinical and pathologic predictors of PSA outcome. RESULTS: The independent predictors of time to PSA failure included a percentage of positive prostate biopsies of greater than 34% (P: < or =.009), PSA level greater than 10 ng/mL (P: < or =.01), seminal vesicle invasion (P: =. 02), prostatectomy Gleason score of 8 to 10 (P: =.04), and positive surgical margins (P: =.0001). Predictions of 2-year PSA failure rates and bootstrap estimates of the 95% confidence intervals were arranged in a tabular format, stratified by independent clinical and pathologic predictors of PSA outcome. CONCLUSION: Patients who are most likely to benefit from effective adjuvant systemic therapy after RP can be identified using readily available clinical and pathologic data.     

根治性前列腺切除术后病理大切片与常规切片的对比分析

背景与目的：在根治性前列腺切除术(radical prostatectomy,RP)组织标本中,应用病理大切片技术可以全面观察组织,其在病理诊断、形态学研究方面拥有独特的优势。但是由于制作技术、设备限制、工作量较大等原因,目前在临床上尚未常规开展。本研究通过比较RP后行常规切片及病理大切片患者的临床及病理变量,评价RP后病理大切片技术在前列腺癌诊断中的意义。方法：选择2012年12月-2014年2月在复旦大学附属肿瘤医院行RP后做病理大切片的229例前列腺癌患者作为研究组,同时选取2010年1月-2012年6月行RP后做常规病理切片的393例前列腺癌患者作为对照组,对比分析包括两组患者年龄,术前PSA值,术前是否接受新辅助内分泌治疗,前列腺癌确诊方式,确诊时Gleason评分、临床分期,RP后Gleason评分、病理分期、手术切缘、前列腺包膜外侵犯、精囊侵犯、术后盆腔淋巴结转移等变量。结果：两组患者术前临床及病理变量：RP后病理Gleason评分、病理分期、前列腺包膜外侵犯情况、术后盆腔淋巴结转移差异均无统计学意义(P>0.05),但是研究组患者手术切缘及精囊侵犯的阳性率明显高于对照组,差异有统计学意义(26.2% vs 17.6%,P=0.010;23.1% vs 17.0%,P=0.025)。结论：应用病理大切片技术可明显提高前列腺标本切缘阳性及精囊侵犯的阳性检出率,因此病理大切片技术值得在前列腺癌病理诊断中推广。     

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。     

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.     

Which patients with newly diagnosed prostate cancer need a radionuclide bone scan? An analysis based on 631 patients

Purpose: Although radionuclide bone scans are frequently recommended as part of the staging evaluation for newly diagnosed prostate cancer, most scans are negative for metastases. We hypothesized that Gleason score, prostate-specific antigen (PSA), and clinical stage could predict for a positive bone scan (BS), and that a low-risk group of patients could be identified in whom BS might be omitted.

Methods: All patients who had both pathologic review of their prostate cancer biopsies and radionuclide BS at our institution between 1/90 and 5/96 were studied. Gleason score, PSA, and clinical stage (AJCC, 4th edition) were evaluated by univariate and multivariate analyses for their ability to predict a positive BS. Groups analyzed were Gleason of 2–6 vs. 7 vs. 8–10; PSA of 0–15 vs. greater than 15–50 vs. greater than 50; and clinical stage of T1a–T2b vs. T2c–T4. Univariate analysis using χ² and multivariate analysis using logistic regression were performed.

Results: Of the 631 consecutive patients, 88 (14%) had positive BS. Multivariate analysis (64 excluded due to missing PSA and/or clinical stage) showed Gleason score, PSA, and clinical stage to be significant independent predictors for positive BS (p < 0.002, p < 0.001, p < 0.001, respectively). The odds ratios were 5.25 (confidence interval [CI], 3.43–8.04) for PSA > 50 vs. 0–15; 2.25 (CI, 1.43–3.54) for Gleason of 8–10 vs. 2–6; 2.15 (CI, 1.54–2.99) for clinical stage T2c–T4 vs. T2b or less. Three of 308 (1%) had a positive BS in patients with Gleason 2–7, PSA of 50 or less, and clinical stage of T2b or less. In the subset of the same risk group with PSA of 15 or less, all 237 had negative bone scans. In patients with PSA greater than 50, 49/99(49.5%) had positive BS.

Conclusion: Gleason score, PSA, and clinical stage were independent predictors for a positive radionuclide BS in newly diagnosed prostate cancer patients. PSA is the major predictor for positive BS. About one-half of the patients analyzed were in the low-risk group (Gleason 2–7, PSA ≤ 50, clinical stage ≤ T2b) and elimination of BS in these patients would result in considerable economic savings.     

Radiotherapy for prostate cancer: should the seminal vesicles be considered target?

During radiotherapy for prostate cancer, the ability to predict occult seminal vesicle invasion is important since irradiation of the entire seminal vesicles necessitates enlarging the radiation fields beyond what is usually used to irradiate the prostate gland alone. We analyzed the records of 302 patients with clinical Stage T1 or T2 adenocarcinoma of the prostate treated with radical surgery at Duke University Medical Center between 1970 and 1983. Univariate and multivariate analyses were used to examine the relationship between the risk of occult seminal vesicle involvement (defined herein as histologic involvement of the seminal vesicles not detected by physical or radiologic examination) and the following factors: histologic grade, age, clinical stage, and preoperative acid phosphatase. Among 249 patients with complete information, increasing histologic grade (p < 0.001) and clinical stage (p < 0.04) were found to be the strongest predictors of occult seminal vesicle invasion. Conversely, seminal vesicle invasion was very unusual in well-differentiated T1-T2 tumors (6%). This low risk group represented 28% (70/249) of this patient population. There appears to be a substantial subset of patients with well differentiated T1 or T2 tumors who are at very low risk for occult seminal vesicle involvement and in whom the seminal vesicles can be excluded from the target volume. The reduction in target volume may reduce normal tissue reactions, facilitate dose escalation, and possibly increase local control rates.     

Optimizing patient selection for dose escalation techniques using the prostate-specific antigen level, biopsy gleason score, and clinical T-stage

Purpose: Ideal candidates for 3D dose escalation conformal radiation or external beam + implant therapy are identified on the basis of the prostate-specific antigen (PSA) level, biopsy Gleason score, and the 1992 American Joint Commission Cancer (AJCC) clinical T-stage.

Methods and Materials: The pathologic findings of 1742 men with clinical stage T1c,2 prostate cancer managed with a radical prostatectomy (RP) between 1990 and 1998 were subjected to a logistic regression multivariable analysis. The endpoints examined included pathologic organ–confined (OC), specimen-confined (SC), and margin (M) or seminal vesicle (SV) positive disease. SC disease was defined as extracapsular extension (ECE) with a negative surgical margin. The clinical factors tested included PSA level, biopsy Gleason score, and the 1992 AJCC clinical T-stage. PSA failure–free (bNED) survival was calculated according to the method of Kaplan and Meier.

Results: Significant negative predictors of pathologic OC–disease or positive predictors of M⁺ or SV⁺ disease included a PSA > 10 ng/ml (p < 0.0001), biopsy Gleason score ≥7 (p ≤ 0.0004), and ≥ T2b disease (p ≤ 0.03). Only biopsy Gleason score 7 (p = 0.0006) and PSA 10–15 ng/ml (p = 0.04) were significant predictors of SC disease. The estimates of 5-year bNED survival were 80%, 62%, and 35% (p < 0.0001) for patients having a low, intermediate, or high likelihood of having M⁺ or SV⁺ disease respectively.

Conclusions: Patients most likely to derive a survival benefit from the improved local control possible using dose escalation techniques were those who had both a low risk of having occult micrometastatic disease (<25% M⁺ or SV⁺) and a reasonable likelihood of remaining disease-free after RP (>50% 5-year bNED). These patients included those having T1c, 2a, PSA > 10–15 ng/ml, and biopsy Gleason ≤6 or T1c, 2a, 2b, PSA ≤ 10 ng/ml, and biopsy Gleason ≤ 7 prostate cancer.     

Relationship between prostate volume, prostate-specific antigen nadir, and biochemical control

PURPOSE: In patients treated with definitive three-dimensional conformal radiotherapy (3D-CRT) for localized prostatic adenocarcinoma, we sought to evaluate the relationship between pretreatment prostate gland volume and posttreatment prostate-specific antigen (PSA) nadir, as well as the relationship of prostate volume and PSA nadir with biochemical control (bNED). Two subgroups were studied: favorable (PSA <10 ng/mL, Gleason score 2-6, and T1-T2A) and unfavorable (one or more: PSA >/=10 ng/mL, Gleason score 7-10, T2B-T3). MATERIALS AND METHODS: A total of 655 men (n = 271 favorable and 384 unfavorable) were treated with 3D-CRT alone between May 1989 and November 1997. All patients had information on prostate volume and a minimum follow-up of 24 months (median 56, range 24-126). Of the 655 men, 481 (n = 230 favorable and 251 unfavorable) remained bNED at time of analysis, with biochemical failure defined in accordance with the American Society for Therapeutic Radiology and Oncology consensus definition. Factors analyzed for predictors of bNED included pretreatment prostate volume, posttreatment PSA nadir, pretreatment PSA, palpation T stage, Gleason score, center of the prostate dose, and perineural invasion (PNI). We also analyzed pretreatment prostate volume and its correlation to prognostic factors. For bNED patients, the relationship between PSA nadir and prostate volume was evaluated. RESULTS: On multivariate analysis, prostate volume (p = 0.04) and palpation T stage (p = 0.02) were the only predictors of biochemical failure in the favorable group. On multivariate analysis of the unfavorable group, pretreatment PSA (p <0.0001), Gleason score (p = 0.02), palpation T stage (p = 0.009), and radiation dose (p <0.0001) correlated with biochemical failure, and prostate volume and PNI did not. For all 481 bNED patients, a positive correlation between pretreatment volume and PSA nadir was demonstrated (p <0.0001). Subgroup analysis of the favorable and unfavorable patients also demonstrated a positive correlation between prostate volume and PSA nadir (p = 0.003 and p = 0.0002, respectively). Using multiple regression analysis, the following were found to be predictive of PSA nadir in all bNED patients: prostate volume (p <0.0001), pretreatment PSA (p <0.0001), palpation T stage (p = 0.0002), and radiation dose (p = 0.0034). Gleason score and PNI were not predictive. For the favorable group, palpation T stage (p = 0.0006), pretreatment PSA (p = 0.0083), prostate volume (p = 0.0186), and Gleason score (p = 0.0592) were predictive of PSA nadir, and PNI and radiation dose were not predictive. In the unfavorable group, prostate volume (p = 0.0024), radiation dose (p = 0.0039), pretreatment PSA (p = 0.0182), and palpation T stage (p = 0.0296) were predictive of PSA nadir, and Gleason score and PNI were not predictive. CONCLUSION: This report is the first demonstration that prostate volume is predictive of PSA nadir for patients who are bNED in both favorable and unfavorable subgroups. PSA nadir did not correlate with bNED status in the favorable patients, but it was strongly predictive in the unfavorable patients. Prostate gland volume was also predictive of bNED failure in the favorable but not the unfavorable group.     

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.     

Predictors of delayed therapy after expectant management for localized prostate cancer in the era of prostate-specific antigen

OBJECTIVE: To identify risk factors for delayed cancer-directed intervention in modern era prostate cancer patients who initially elect expectant management. MATERIALS AND METHODS: An observational, cohort study of expectantly managed patients, diagnosed with clinical T(1-4)NxM0 prostate cancer between 1993 and 2000 was carried out. Data including TNM stage, age, serum prostate-specific antigen (PSA), prostate gland volume by transrectal ultrasound, Gleason score, percent biopsies positive for cancer, imaging results, initial treatment selection, and outcome data were collected on all patients. RESULTS: 192 of 561 patients (34.3%) elected expectant management, and follow-up data were available for 187 (97.4%) patients. With a median follow-up of 3.6 years, 90 (48.1%) patients had a cancer-directed intervention. Gleason score (p = 0.0097) and percent of positive biopsy cores (p = 0.03) were independent predictors of time to intervention. As expected, PSA doubling time became the most significant predictor of intervention (p = 0.0057) when added to the model. These independent covariates are able to characterize low-, intermediate- and high-risk groups for cancer-directed intervention. CONCLUSIONS: Cancer-directed intervention is common in patients who choose expectant management in the PSA era. Gleason score and percent of positive biopsy cores predict cancer-directed interventions, thus, these patients may be least suitable for expectant management.