18F-PSMA-PET/CT在1例前列腺癌生化复发患者诊断中的应用

正p504s(+),p63(-),CK-H(-),Ki-67(部分+)。2015年4月患者于全麻下行前列腺癌根治术,手术过程顺利。术后病理回报:前列腺癌,肿物大小约3.5cm×2.5cm×2cm,Gleason评分5+4=9分,癌组织侵及外膜,脉管内见癌栓;一侧精囊腺见癌组织,另一侧精囊腺未见癌。术后应用比卡鲁胺与戈舍瑞林内分泌治疗3个月后停药,多次复查血PSA未见明显异常。2018年11月(前列腺癌根治术后4年)患者于我院复查,结合患者近4次血PSA水平:2017年12月及2018年3、4、10月分别为0.09ng/mL及0.26、0.30、0.55ng/mL。考虑患者前列腺癌     

经直肠超声引导下“6+X”点法前列腺穿刺活检术在PSA值＞20ng/ml患者前列腺癌诊断中的价值

目的 探讨经直肠超声引导下“6+X”前列腺穿刺活检术在PSA值＞20ng/ml之间患者前列腺癌诊断中的价值.方法 回顾性分析57例血清PSA值＞20ng/ml之间疑似前列腺癌患者临床资料,所有患者均行经直肠超声引导下前列腺穿刺术活检.结果 前列腺癌54例,急性前列腺炎3例.结论 经直肠超声引导下“6+X”前列腺穿刺活检是诊断PSA值＞20ng/ml之间患者前列腺癌的一种安全有效的检查方法.     

经直肠超声引导下经会阴125I粒子永久植入治疗前列腺癌的初步经验

目的探讨经直肠超声引导下经会阴125I粒子永久植入治疗前列腺癌的疗效和并发症。方法本组前列腺癌患者5例。年龄61￣83岁,平均70.4岁。临床分期T2bN0M0者2例,T3aN0M0者3例。Gleason评分6分者2例,7分者1例,8分者2例。术前前列腺特异性抗原(PSA)4.5￣17.5ng/ml。T3a期患者植入治疗前先行内分泌治疗。术前制定治疗计划,经直肠超声引导下经会阴125I粒子永久植入操作。术后观察PSA水平变化,连续3次PSA升高即为生化复发,观察术后尿路和直肠并发症发生情况。结果5例患者均术后恢复顺利。术后随访18个月,PSA均明显下降,PSA为0.1ng/ml者3例,0.01ng/ml者1例,0.04ng/m1者1例。5例患者术后均出现不同程度的尿路刺激症状,但6个月后逐渐好转。4例术后出现排便次数增多,术后3个月均好转。未发现尿失禁、直肠溃疡等并发症。结论经直肠超声引导下经会阴125I粒子永久植入治疗前列腺癌的疗效确切,创伤较小。     

徒手TRUS引导下经会阴前列腺活检的临床应用探讨

目的:探讨徒手"12+X"法TRUS引导下经会阴前列腺活检术诊断前列腺癌的临床应用价值。方法:2014年12月~2015年12月,对74例可疑前列腺癌患者行经直肠B超引导下18G自动穿刺活检针行双侧外周带12点法系统穿刺,其中直肠指诊(DRE)触及结节24例,超声提示异常回声14例,前列腺核磁提示异常信号30例;前列腺特异性抗原(PSA)<4ng/ml者14例,PSA 4~10ng/ml 25例,PSA>10ng/ml者35例。同时对每个可疑病灶进行1~2针靶向穿刺。回顾性分析穿刺的阳性率和并发症。结果:成功对74例患者进行徒手"12+X"法TRUS引导下经会阴前列腺活检术。年龄43~81岁,中位年龄72岁;PSA 1.9~500ng/ml,中位PSA17.8ng/ml。经病理诊断,前列腺癌23例,阳性率31.1%,穿刺阴性病例中3例TURP术后病理诊断结果为前列腺癌;2例首次穿刺阴性,6个月后重复穿刺时发现前列腺癌。低危前列腺癌(Gleason≤6分)、中危前列腺癌(Gleason=7分)和高危前列腺癌(Gleason≥8分)分别为13.1%、30.4%和56.5%。其余51例为良性前列腺增生或合并前列腺炎症。术后短暂和轻度的肉眼血尿6例(8.1%),均在1~3d后缓解,5例(6.8%)轻度发热,2例(2.7%)会阴部轻度不适。无脓毒症、急性尿潴留等严重并发症的发生。结论:徒手"12+X"法TRUS引导下经会阴前列腺活检安全可行,阳性率稳定,值得在临床上进一步推广。     

低血清PSA型前列腺癌的回顾性研究

目的:探讨低血清前列腺特异抗原(prostate-specific antigen,PSA)型前列腺癌的临床特证。方法:回顾性分析10例低血清PSA型前列腺癌患者的临床资料:10例患者因下尿路梗阻或骨痛或体检异常入院,入院时血清PSA值平均为1.968ng/ml。直肠指诊、经直肠前列腺超声、MRI检查异常,行穿刺和(或)前列腺电切术,其中2例前列腺小细胞癌患者,1例行药物去势+抗雄激素治疗,另1例行前列腺电切术+药物去势+抗雄激素治疗;7例前列腺腺癌患者,2例行药物去势+抗雄激素治疗,1例行手术去势+抗雄激素治疗,2例行腹腔镜前列腺癌根治术,2例行前列腺电切+药物去势+抗雄激素治疗;1例鳞癌患者行前列腺电切术+药物去势+抗雄激素治疗。结果:术后经病理检查确诊。7例前列腺腺癌Gleason评分,6例≥7分,1例=4分。10例患者中,T3期以上患者8例,其中3例有骨转移。10例患者术后平均随访18个月,4例死亡,3例病情进展,3例病情无进展。结论:低血清PSA型前列腺癌发病多隐匿,恶性度较高,诊断及随访不依赖血清PSA;内分泌治疗效果不理想,术后随访时需定期行影像学检查,以明确疾病有无进展。     

125I 放射性粒子植入术联合间歇性内分泌疗法治疗局部中高危前列腺癌

目的 探讨¹²⁵I放射性粒子植入术联合间歇性内分泌疗法治疗局部中高危前列腺癌的临床价值。方法 前列腺癌患者25例，年龄 64～85 岁，平均年龄75岁，前列腺特异性抗原（PSA）：10.3～354.8 ng/mL，Gleason 评分：7～9 分，临床分期T2～T3N0M0。椎管内麻醉，截石位，直肠超声从前列腺基底到尖部进行扫描，图像传送至计算机计划系统进行三维重建和术中计划，根据计划行直肠超声引导下经会阴¹²⁵I放射性粒子植入术，术后联合全部雄激素阻断疗法。当PSA达到0 ng/mL，并稳定2个月后停止内分泌治疗，当PSA连续3次上升，则重新开始内分泌治疗。结果所有患者手术均顺利，植入粒子85～110粒，平均93粒。术后随访8～20个月，平均12个月。术后3～6个月所有患者的PSA都降到正常范围，其中10例患者PSA未达到0 ng/mL，未停药。5例患者术后5～16个月，出现PSA反弹，再次用药3～5个月PSA值达到0 ng/mL。2例患者转变为激素非依赖性并出现骨转移。目前17例患者的PSA值在0～1.2 ng/mL之间，其中10患者PSA< 0.2 ng/mL。近期出现的并发症有轻至中度尿路刺激征24%（6/25），急性尿潴留8%（2/25），直肠刺激征和血便16%（4/25），多数患者症状随访1年后缓解。结论 对于局部晚期中高危前列腺癌，¹²⁵I放射粒子植入术联合间歇性内分泌疗法是一种安全有效的治疗方法。     

腹腔镜下前列腺癌根治术后切缘阳性的相关因素分析

目的 探讨腹腔镜下前列腺癌根治术后切缘阳性的相关因素. 方法 2004年2月至2007年9月,采用腹膜外途径行腹腔镜下前列腺癌根治术33例.患者年龄57～78岁,平均70岁.术前均经病理证实前列腺癌诊断.Gleason评分3+3者14例(43%)、3+4者11例(33%)、4+3者6例(18%)、4+4者2例(6%),临床分期T1a～T1b 4例(12%)、T1c14例(43%)、T2a～T2b 5例(15%)、T2c 10例(30%).多因素回归分析比较根治术后标本切缘阳性与阴性组临床及生物学参数指标. 结果 腹腔镜下完成前列腺癌根治术31例,中转开放手术2例.术后病理报告切缘阳性9例(27%)、阴性24例(73%).切缘阳性组与阴性组患者术前临床分期T2c分别为6例(67%)和4例(17%)(P=0.010),术后Gleason评分＞7分者分别为3例(33%)和0例(P=0.015),术前PSA＞20ng/ml分别为4例(44%)和5例(21%)(P=0.178),直肠指诊可触及结节或局部质硬者分别为4例(44%)和9例(38%)(P=0.509).多因素回归分析结果显示:临床分期T2c与切缘阳性呈独立正相关关系(OR=24.69),T2c患者术后切缘阳性率明显增高.术前Gleason评分＞7分者切缘阳性率增高,PSA＞20 ng/ml者切缘阳性率有增高趋势,但二者需结合临床分期等指标综合判断对术后切缘阳性的影响.直肠指诊触及结节或质硬者切缘阳性率略增高,可作为参考指标. 结论 影响腹腔镜下前列腺癌根治术后切缘阳性的因素为临床分期、术前病理Gleason评分、总PSA和直肠指诊.临床分期可以作为预测术后切缘阳性的独立相关因素,≥T2c期的患者术后切缘阳性率明显增加.Gleason评分＞7分、PSA＞20 ng/ml作为重要参考指标,应结合临床分期综合分析;直肠指诊有结节或质硬可作为参考指标.     

经直肠超声引导下“10+X”点法前列腺穿刺活检术在PSA值介于4～20ng/ml之间患者前列腺癌诊断中的价值

目的 探讨经直肠超声引导下“10 +X”前列腺穿刺活检术在PSA值介于4 ～20ng/ml之间患者前列腺癌诊断中的价值。方法 回顾性分析226例血清PSA值介于4～20ng/ml之间疑似前列腺癌患者临床资料,所有患者均行经直肠超声引导下前列腺穿刺术活检。结果 前列腺癌47例,前列腺增生158例,前列腺炎11例,前列腺上...     

血清PSA值与穿刺标本Gleason评分预测前列腺癌病理分级

目的 探讨准确有效预测前列腺癌病理分级的方法.方法 分析75例前列腺癌患者术前血清PSA水平、穿刺活检标本和前列腺癌根治术后标本Gleason评分资料,对血清PSA水平与根治术后标本Gleason评分进行等级相关分析,对穿刺活检标本与根治术后标本Gleason评分进行配对秩和检验.结果 75例患者术前血清PSA值4～230 ng/ml,平均33.5 ng/ml;穿刺活检标本Gleason评分2～9分,平均(4.4±2.3)分;根治术后标本Gleason评分2～10分,平均(4.8±2.5)分.术前血清PSA水平与根治术后标本Gleason评分呈正相关(rs=0.279,P=0.015),穿刺活检标本与根治术后标本Gleason评分差异有统计学意义(P=0.011).结论 前列腺癌患者术前血清PSA水平越高,根治术后标本Gleason评分也越高;穿刺标本Gleason评分有低估的缺点,必要时应行病理分级后再评估.     

Gleason10分前列腺癌患者的临床特点分析

目的 观察Gleason 10分前列腺癌患者的临床诊疗及疾病变化过程,总结该类前列腺癌患者的临床特点及预后影响因素. 方法 2005年1月至2010年5月,21例初诊为前列腺癌、Gleason 10分、行手术去势加抗雄激素治疗的患者纳入本研究.初诊年龄56～85岁,平均73岁.PSA 8.9～261.0 ng/ml,平均60.8 ng/ml,其中6例PSA≤20 ng/ml.行核素骨扫描发现骨转移16例.予双侧睾丸切除术加氟他胺或比卡鲁胺全雄激素阻断治疗.术后1个月复查PSA,以后每3个月随访PSA.治疗后6个月为单纯内分泌治疗观察终点.6个月内PSA未降至＜4 ng/ml且无远处转移者加用局部外放射治疗,伴骨转移者使用基于多西他赛与泼尼松的全身化疗.患者死亡为研究终点.结果 15例初诊PSA＞ 20 ng/ml患者中,5例治疗后6个月内血清PSA未降至正常水平,其中4例伴骨转移.该4例子全身化疗后PSA均未降至正常水平,3例1年内死亡,1例诊断后19个月死亡,1例疾病局限患者予外放射治疗,PSA下降至正常水平8个月后出现肿瘤进展,诊断后11个月死亡.10例治疗后6个月内血清PSA降至正常水平,其中3例分别于诊断后第19、28、36个月死于肿瘤,7例存活.6例初诊时PSA≤20 ng/ml患者中3例治疗后6个月内PSA未降至正常水平,其中2例伴骨转移予化疗后于1年内死亡;1例PSA下降至正常水平但仍出现肿瘤进展,全身多发骨转移,化疗无效,1年内死亡;1例4年后因前列腺癌死亡;1例随访6个月,PSA降至0.07 ng/ml. 结论 Gleason 10分前列腺癌肿瘤进展迅速,抗雄激素治疗疗效不佳,行伞雄激素阻断后6个月内PSA无法下降至正常水平患者病情进展凶险.初诊PSA≤20 ng/ml且病理证实Gleason 10分者可能预示预后不佳.     

Prostate cancer detection at low prostate specific antigen

PURPOSE: At low prostate specific antigen (PSA) the indication for prostate biopsy is usually an abnormal digital rectal examination. We evaluate the diagnostic value of PSA, digital rectal examination, transrectal ultrasonography and tumor characteristics at low PSA (0 to 4.0 ng./ml.). We confirm and add to recent evidence that digital rectal examination has a low predictive value and that many significant cancers at this PSA range may be missed. MATERIALS AND METHODS: From 1994 to 1997 a total of 10,523 participants 54 to 74 years old were randomized to screening in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer. Of the participants 9,211 (87.5%) had PSA less than 4.0 ng./ml., and underwent digital rectal examination and transrectal ultrasonography. Expected rates of prostate cancer detection were calculated using logistic regression analysis. Radical prostatectomy was performed in about half of the 478 men diagnosed with prostate cancer. Tumors were characterized by pT category, Gleason score and cancer volume in 166 processed radical prostatectomy specimens. In 50 of these cases PSA was 0 to 4.0 ng./ml. RESULTS: The positive predictive value of digital rectal examination and transrectal ultrasonography at PSA 0 to 4.0 ng./ml. was only 9.7%. Positive predictive value strongly depended on PSA. Sensitivity was calculated by using estimates of the prevalence of sextant biopsy detectable prostate cancers. Of 760 detectable cancers 478 (67%) were diagnosed irrespective of PSA in men screened with digital rectal examination, transrectal ultrasonography and PSA. Only 127 of 348 detectable prostate cancers (36.5%) were actually diagnosed in men with PSA 2 to 4 mg./ml. The importance of these missed cancers was evaluated with parameters of tumor aggressiveness within PSA ranges. CONCLUSIONS: Approximately half of the tumors missed with PSA 0 to 4 ng./ml. had aggressive characteristics (Gleason score 7 or greater, Gleason 4-5 components) and were organ confined. These tumors should be diagnosed and treated according to the present understanding of their natural history. More sensitive and selective screening strategies are needed. Presently a wrong "window of opportunity" is used for early detection of prostate cancer.     

The clinical potential of pretreatment serum testosterone level to improve the efficiency of prostate cancer screening

OBJECTIVES: The aim of the present study was to evaluate the clinical value of the pretreatment serum testosterone (T) level as a potential predictor of prostate cancer risk in screening for prostate cancer. MATERIALS AND METHODS: The subjects were 420 patients suspected of having prostate cancer who underwent prostate biopsy, and whose pretreatment T levels were recorded. We checked for association between the presence of prostate cancer and the following clinical factors: pretreatment serum T level, age, pretreatment prostate-specific antigen (PSA) level, digital rectal examination findings, ratio of free to total PSA, prostate volume, and PSA density (PSAD). RESULTS: Overall, there was no significant difference in mean pretreatment T level between patients diagnosed with cancer (3.9+/-2.4 ng/ml) and patients diagnosed with benign prostate disease (BPD; 3.7+/-1.7 ng/ml); diagnosis was based on prostate biopsy. However, among patients with PSA <10 ng/ml, the pretreatment T level was significantly higher in patients diagnosed with prostate cancer (4.2+/-2.6 ng/ml) than in patients diagnosed with BPD (3.6+/-1.4 ng/ml) (p=0.007); a similar trend was observed among patients with PSAD <0.15 ng/ml/cc. Multivariate analysis indicated that pretreatment T level was an independent significant predictor of positive prostate biopsy (p=0.020). Additionally, the serum T level was significantly lower in patients with a Gleason score >or=7 (3.7+/-2.1 ng/ml) versus a score <7 (4.2+/-1.7 ng/ml) (p=0.030). Also, serum T levels were significantly higher in well-differentiated prostate cancer (4.8+/-2.1 ng/ml) versus moderately differentiated (3.8+/-1.3 ng/ml) or poorly differentiated (3.7+/-1.4 ng/ml) (p<0.01). CONCLUSIONS: Among relatively low-risk patients, serum T level was an independent significant predictor of positive prostate biopsy, suggesting that the efficiency of prostate cancer screening can be improved by including measurement of serum T level.     

High-grade prostate cancer is associated with low serum testosterone levels

BACKGROUND: The aim of this study was to assess whether low serum testosterone levels in men with newly diagnosed prostate cancer have an association to the endocrine status, prostate-specific antigen (PSA) levels, Gleason score, and androgen receptor expression. METHODS: Besides a full clinical work-up, the following hormones were quantified in men with newly diagnosed prostate cancer by serum analysis: total testosterone, human luteinising hormone (hLH), human follicle stimulating hormone (hFSH), estradiol, and dehydroepiandrostendione (DHEA). In a subgroup of men, androgen receptor expression was determined immunohistochemically. RESULTS: One hundred and fifty six patients (65.7 +/- 8.5 yrs) with a mean PSA of 29.8 ng/ml (median: 7.4 ng/ml) were analysed. Fifty-two patients (33%) had a partial androgen deficiency (serum testosterone < 3.0 ng/ml). These men had lower hLH (3.3 vs. 5.9 mIU/ml), hFSH (6.2 vs. 8.4 mIU/ml), and estradiol (18.8 vs. 29.1 pg/ml) serum levels. Mean Gleason score was higher (7.4 vs. 6.2) in men with a low serum testosterone, PSA-levels were lower (25.3 vs. 31.9 ng/ml). Mean testosterone levels decreased from 4.1 +/- 1.7 ng/ml in patients with Gleason scores < or = 5 to 2.8 +/- 2.7 ng/ml with Gleason scores > or = 8. Androgen receptor expression was higher in patients with low serum testosterone. CONCLUSIONS: Patients with high Gleason score prostate cancer have lower testosterone and estradiol serum levels. The fact that gonadotropins were lower in parallel suggests a tumor-mediated suppression of the hypothalamic-pituitary-gonadal hormone axis particularly in men with high Gleason score tumours.     

Prostate cancer detection in Black and White men with abnormal digital rectal examination and prostate specific antigen less then 4 ng./ml

PURPOSE: Prostate cancer is more common in black than in white American men. Experience in a longitudinal prostate cancer screening program implies that cancer detection is greater in black than in white men with an abnormal digital rectal examination and prostate specific antigen (PSA) less than 4 ng./ml. We investigated potential racial differences in cancer detection in men treated in clinical practice who had an abnormal digital rectal examination and PSA less than 4 ng./ml. MATERIALS AND METHODS: Between January 1992 and December 1999 prostate biopsy was done at a Veterans Affairs Medical Center in 179 black and 357 white men with an abnormal digital rectal examination, PSA less than 4 ng./ml. and no history of prostate surgery. Significant racial differences in demographic and clinical parameters were limited to PSA, which was higher in black men (p = 0.01). RESULTS: Cancer was detected in 38 black (21%) and 65 white (18%) men (p = 0.42). There were no significant racial differences in the PSA adjusted cancer detection rate or in the Gleason score of detected disease. In men with PSA less than 1.0, 1.0 to 1.9, 2.0 to 2.9 and 3.0 to 3.9 ng./ml. the detection rate was 4%, 15%, 27% and 29%, respectively. CONCLUSIONS: In clinical practice prostate cancer detection appears to be equivalent in black and white men when an abnormal digital rectal examination is the only indication of malignancy.     

Active surveillance; a reasonable management alternative for patients with prostate cancer: the Miami experience

OBJECTIVE

To examine the outcome of patients diagnosed with ‘low‐risk’ prostate cancer managed by active surveillance (AS).

PATIENTS AND METHODS

In all, 157 men with localized prostate cancer were followed on AS. The inclusion criteria for AS included: Gleason score of ≤ 6, a serum prostate‐specific antigen (PSA) level of ≤15 ng/mL, stage ≤ T2, low‐volume disease and >12 months of follow‐up. The follow‐up was rigorous, with PSA tests and a digital rectal examination every 3 months for 2 years, and a repeat biopsy 6–12 months after the initial diagnosis and yearly when indicated. Continuance of AS was based on the PSA doubling time, re‐biopsy score, Gleason score, tumour volume, stage progression and patient preference.

RESULTS

In all 99 patients met the inclusion criteria; their mean age at diagnosis was 66 years, their mean PSA level 5.77 ng/mL and the mean follow‐up 45.3 months. On initial repeat biopsy, 63% had no cancer and 34% had a Gleason sum of ≤ 6. Eight patients were treated (three with hormones; five with curative intent); two had radical prostatectomy (one had pT2c pNO Gleason 7 disease); three had radiotherapy. The probability is that 85% would remain treatment‐free at 5 years; no patient died from prostate cancer. The PSA doubling time and clinical stage at diagnosis were predictive of progression.

CONCLUSION

Patients who are followed on AS must be selected using narrowly defined inclusion criteria and closely followed with a standard regimen of PSA testing, digital rectal examination and repeat biopsy.     

Percent free prostate specific antigen in the total prostate specific antigen 2 to 4 ng./ml. range does not substantially increase the number of biopsies needed to detect clinically significant prostate cancer compared to the 4 to 10 ng./ml. range

PURPOSE: Percent free prostate specific antigen (PSA) is useful to select patients for prostate biopsy with total PSA 4 to 10 ng./ml. However, 20% of men with PSA between 2.6 and 4 ng./ml. harbor significant prostate cancer and percent free PSA has been suggested to aid in the decision to biopsy in this total PSA range as well. Concerns exist that the number of biopsies needed to detect 1 cancer in this range may be inappropriately high. In a prospective referral population we evaluated sensitivity and specificity of various percent free PSA cutoffs and determined the biopsy-per-cancer ratio in the PSA 2 to 4 ng./ml. range in men with a benign digital rectal examination, and report on the biological nature of the detected cancers based on Gleason score. Results were compared to those obtained from a reference group of patients (PSA 4 to 10 ng./ml., benign digital rectal examination) from the same prospective referral cohort. MATERIALS AND METHODS: Total PSA and free PSA were measured and percent free PSA was calculated. Of the initial 1,602 men 756 had a benign digital rectal examination and PSA 4 to 10 ng./ml., and 219 had a benign digital rectal examination and PSA 2 to 4 ng./ml. Sensitivity, specificity, the number of true positive (evidence of cancer) and false-positive (no evidence of cancer) biopsies were determined. The ratio of true positive biopsies-to-all biopsies performed was used to determine the biopsy-per-cancer ratio. Gleason score of the detected cancers was evaluated. The procedure was repeated for the PSA 4 to 10 ng./ml. range. RESULTS: In the PSA 4 to 10 ng./ml. range a sensitivity of 63.7% to 92.5% with a specificity of 57.5% to 18.7% was found when percent free PSA was 18% to 25%. On average 3 biopsies were needed to detect 1 cancer. When PSA was 2 to 4 ng./ml. sensitivity was 46.3% to 75.6% and specificity was 73.6% to 37.6% when the same percent free PSA cutoff was examined. Calculation of the biopsy-per-cancer ratio for various percent free PSA cutoffs revealed that 3 to 5 biopsies were needed to find 1 cancer. Of 41 cancers detected in the PSA 2 to 4 ng./ml. range 6 had a Gleason score 5. The majority (28 of 41) of cases had a Gleason score of 6. Gleason score was 7 in 5 patients and 8 in 1. CONCLUSIONS: In the PSA 4 to 10 ng./ml. range high sensitivity for prostate cancer detection is critical and 3 biopsies are needed to detect 1 cancer. In the PSA 2 to 4 ng./ml. range a percent free PSA cutoff of 18% to 20% detected about 50% of cancers while sparing up to 73% of unnecessary biopsies with a biopsy-to-cancer ratio of 3 to 4:1. Percent free PSA can be applied to the PSA 2 to 4 ng./ml. range to detect prostate cancer and only moderately increases the number of biopsies needed to detect 1 significant cancer compared to the greater than 4 to 10 ng./ml. range.     

Characterizing prostatic adenocarcinomas in men with a serum prostate specific antigen level of < 4.0 ng/mL

OBJECTIVE: To characterize prostate cancer in men undergoing radical prostatectomy who have a prostate-specific antigen (PSA) level of < 4.0 ng/mL, hypothesizing that a low PSA is not caused by diminished tumour production of PSA, nor does it signify clinically insignificant disease. PATIENTS AND METHODS: Seventy-nine men (mean age 59.3 years, range 43-77) with a PSA level of < 4.0 ng/mL were identified from 702 who had a radical prostatectomy between 1994 and 2000. Demographic and clinical data were analysed; pathological specimens were evaluated by routine haematoxylin and eosin staining and immunohistochemistry with anti-PSA antibody, for both pathological staging and grading, and for the presence of PSA production. Tumours were classified as 'clinically insignificant' if the tumour volume was < 0.5 mL and the Gleason score < 7. RESULTS: The mean (SD, range) preoperative PSA level was 3.04 (0.85, 0.8-3.8) ng/mL Indications for biopsy included an abnormal digital rectal examination (61%), a PSA velocity of > 0.75 ng/mL/year (12%), a strong family history of prostate cancer (3%), obstructive urinary symptoms (2%), or no obvious indication (23%). Thirty-eight (48%) tumours were clinically insignificant. Of 41 clinically significant cancers, 13 had a final Gleason score of > or = 7, 20 had extraprostatic extension and 11 had a tumour volume of > or = 10 mL Of the 79 prostate cancer specimens 78 stained strongly for PSA; the exception was a Gleason 9 tumour. With a mean (range) follow-up of 3.5 (0.18-6) years only one patient had a biochemical recurrence (PSA > or = 0.1 ng/mL). CONCLUSIONS: Most prostate cancers in men with a PSA level of < 4.0 ng/mL are clinically significant and PSA-producing. Many of these tumours are high-grade, high-volume and extraprostatic. We are currently exploring factors to explain why serum PSA is not elevated in these men, including tumour location, pattern of invasion and microvessel density.     

Histological characteristics and clinical significance of Japanese prostate cancer with low levels of prostate specific antigen of 4.0 ng/ml or lower]

PURPOSE: They set a normal limit of prostate specific antigen (PSA) to 4.0 ng/ml in Tandem R assay at most institutions. We investigated clinical and histological characteristics of prostate cancer based on whole mount step-section histology of radical prostatectomy specimens, and taking notice of Japanese prostate cancer whose levels of PSA are less than 4.0 ng/ml in normal levels. MATERIALS AND METHODS: One hundred and twenty-two patients underwent radical prostatectomy for clinically resectable prostate cancer at University Hospital from February 1992 to April 1997. Clinicopathological findings were stratified according to the preoperative PSA levels in 111 patients without preoperative endocrine therapy. Immunohistochemical study for PSA was conducted in 7 randomly selected patients. RESULTS: Of the patients 22 (19.8%) had normal (4.0 ng/ml or lower) preoperative serum PSA. Mean tumor volume in this PSA range was 1.5 cm3 with one pT 0 case included. Pathologically organ confined, potentially curable disease (< pT 3) was found in 17 (77.3%) patients and extracapsular extension and seminal vesicle invasion in 5 (23.8%), respectively. No patients had positive pelvic lymph nodes. Well differentiated tumors of Gleason scores 2-4 were found in 9 (40.9%) of the patients, moderately differentiated tumors (Gleason scores 5, 6) in 5 (22.7%) and poorly differentiated histology (Gleason scores 7-10) in 7 (31.8%). Sixteen (72.7%) patients had clinically significant tumors (> 0.5 cm3, Gleason score > or = 7). All 7 patients had positive staining for PSA, but its intensity did not correlate with serum PSA levels. CONCLUSIONS: Many prostate cancers found in surgical specimens were clinically significant despite the low levels of PSA and potentially curable by definitive treatment. Age, co-morbidity and other clinicopathological variables as well as PSA levels should all be taken into account when treatment options are discussed.     

Tumor characteristics in screening for prostate cancer with and without rectal examination as an initial screening test at low PSA (0.0-3.9 ng/ml)

BACKGROUND: The value of rectal examination as initial screening test for prostate cancer at low PSA values (0.0-3.9 ng/ml) was determined by evaluating the number and tumor characteristics of the cancers detected. METHODS: Two study populations were subjected to screening with (n = 10,226) and without (n = 10,753) rectal examination as initial screening test. The number of cancers detected at low PSA values for both screening regimens, the corresponding biopsy and radical prostatectomy tumor characteristics were assessed. Possibly harmless cancers were defined as small (< 0.5 ml) organ-confined tumors without Gleason growth-patterns 4/5. RESULTS: At low PSA, 26.6% (117/440) of screen-detected cancers were detected after the evaluation of a suspicious rectal examination. The number of cancers and tumor aggressiveness features were highly associated with serum-PSA level. The proportion of possibly harmless disease steadily declined from 100% (PSA 0.0-0.9 ng/ml) to 15.4% (PSA 3.0-3.9 ng/ml). Rectal examinations were performed unnecessarily in 94.7-100% of cases, when detection of clinically significant disease was aimed at. Using PSA (and a cut-off of 3.0 ng/ml) as the only screening tool, 24.3% (121/498) of screen-detected cancers were in the PSA range 3.0-3.9 ng/ml, and 60.0% were assessed as clinically significant. CONCLUSIONS: Rectal examination as initial screening test for prostate cancer at low PSA values may be replaced by screening using serum-PSA only. At PSA levels below 3.0 ng/ml, 289 rectal examinations are required to find one case of clinically significant disease, and 96 rectal examinations are needed to diagnose prostate cancer of any size, grade, or stage.     

Role of radical prostatectomy in patients with prostate cancer of high Gleason score

BACKGROUND: The routine use of serum prostate-specific antigen (PSA) testing combined with digital rectal examination has lowered tumor volume and clinical-pathological stage of men undergoing radical prostatectomy. Therefore, we may identify more men with poorly differentiated tumors of early clinical stage. In order to identify those who may benefit from radical prostatectomy, we evaluated known prognostic variables in patients with prostate cancer of high Gleason score (8-10). METHODS: Of 652 patients who underwent a radical prostatectomy as monotherapy for clinically localized prostate cancer between March 1991-December 1995, 84 patients with prostatectomy specimen Gleason score 8-10 tumors were identified. Clinical-pathological data were obtained from our prostate cancer database. Gleason score, PSA level, margin status, pathologic stage, and tumor volume were analyzed as general prognostic variables for disease-free survival (DFS). Follow-up ranged from 13-84 months (median, 36.2). Biochemical recurrence was defined as a postoperative PSA elevation greater than 0.4 ng/ml. RESULTS: The DFS for patients with Gleason score 8-10 and pathologically organ-confined disease was 62.5%. DFS was 56.2% for patients with PSA < or =10 ng/ml, compared to 19.2% for patients with serum PSA >10 ng/ml (P = 0.009). Patients with nonspecimen-confined disease (positive margins) had a DFS rate of 26.6% vs. 55% for patients with specimen-confined disease (negative margins) (P = 0.009). On multivariable analysis, only preoperative PSA < or =10 ng/ml (P = 0.02) and surgical margin status (P = 0.04) were significant predictors of DFS. CONCLUSIONS: Surgical margin status and preoperative serum PSA level are independent predictors of DFS for patients with high Gleason score prostate cancer treated by radical prostatectomy as monotherapy. Patients with poorly differentiated prostate cancer treated surgically at an early stage can have a favorable prognosis, especially if negative surgical margins are obtained. A preoperative serum PSA level < or =10 ng/ml carries the greatest likelihood of achieving prolonged DFS in this group of patients.