Is Pelvic Lymph Node Dissection Necessary in Patients with a Serum PSA < 10 ng/ml Undergoing Radical Prostatectomy for Prostate Cancer?

OBJECTIVE: Controversy persists concerning the role of pelvic lymph node dissection (PLND) in patients with preoperative PSA values <10ng/ml undergoing treatment for prostate cancer with a curative intent. The aim of this study was to determine the incidence of lymph node metastasis in this subgroup of patients. METHODS: Patients with clinically localized prostate cancer and a serum PSA<10ng/ml, without neoadjuvant hormonal or radiotherapy, with negative staging examinations who underwent radical retropubic prostatectomy with bilateral extended PLND and with >/=10 lymph nodes detected by the pathologist in the surgical specimen, were included in the study. RESULTS: A total of 231 patients with a median serum PSA of 6.7ng/ml (range 0.4-9.98) and a median age of 62 years (range 44-76) were evaluated. A median of 20 (range 10-72) nodes were removed per patient. Positive nodes were found in 26 of 231 patients (11%), the majority of which (81%) had a Gleason score >/=7 in the surgical specimen. Of the patients with a Gleason score >/=7 in the prostatectomy specimen 25% had positive nodes, whereas only 3% with a Gleason score /=7 in the prostatectomy specimen was 25% after extended PLND. It seems that in this patient group extended PLND, including removal of nodes along the internal iliac vessels, is warranted.     

Is It Necessary to Detect All Prostate Cancers in Men with Serum PSA Levels <3.0 ng/ml? A Comparison of Biopsy Results of PCPT and Outcome-Related Information from ERSPC

CONTEXT: The European Randomized Study of Screening for Prostate Cancer (ERSPC) section Rotterdam was initiated in 1993. Men who initially presented with prostate-specific antigen (PSA) values <3.0 ng/ml were not biopsied (with few exceptions). In the Prostate Cancer Prevention Trial (PCPT) eligible men who initially presented with PSA values <3.0 ng/ml were all biopsied during or at the end of a 7-yr study period. OBJECTIVE: To compare biopsy rates in PCPT and cancer detection rates, interval cancers, and prostate cancer deaths in ERSPC. Report the number of additional biopsies needed to detect these cases using PCPT policy. EVIDENCE ACQUISITION: 21,210 men, aged 55-74 yr, were randomised to screening; 19,970 were actually screened between November 1993 and December 1999. A total of 15,852 initially presented with PSA values of <3.0 ng/ml; after excluding 79 detected at first screens, 15,773 remained as the study population. A second and third screening round followed after 4- and 8-yr intervals. All cancers found in three rounds of screening or as interval cancers during the 12-yr interval were identified and characterised. EVIDENCE SYNTHESIS: Screening for prostate cancer and routine clinical management, comparison of detection rates and outcome data. During the 12-yr observation period, which may be too short, 700 cancers were found, 620 through screening and 80 as interval cancers. None of the screen-detected cases but 6 of the 80 men with interval cancers died of prostate cancer. Applying the positive predictive value of 21.7% of the PCPT trial 3472 cancers would have been detected in ERSPC Rotterdam had all men with PSA values <3.0 ng/ml been biopsied. Assuming 80 interval cancers and 6 deaths from prostate cancer might have been prevented if all 15,773 eligible men had undergone biopsy. CONCLUSIONS: The present data suggest a very much unfavourable "number needed to be biopsied" to find one missed cancer or to detect the deadly interval cancers.     

Are Repeat Biopsies Required in Men with PSA Levels ≤4 ng/ml? A Multiinstitutional Prospective European Study

OBJECTIVES: Pathological and biochemical features of prostate cancers detected on repeat biopsies in men with total PSA level between 2.0 and 4 ng/ml were evaluated and compared to those cancers detected on first biopsy. METHODS: 315 men with PSA level between 2.0 and 4 ng/ml underwent transrectal ultrasound guided sextant biopsy and two additional transition zone biopsies (Octant Biopsy). All subjects whose biopsy samples were negative for prostate cancer underwent a repeat biopsy after 6 weeks. Those with clinically localized cancers were offered surgery or radiation therapy. Pathological and clinical features of patients diagnosed with prostate cancer on initial and repeat biopsy were compared. RESULTS: Cancer detection rates on first and second biopsy were 24% (75/315) and 13% (29/224), respectively. Overall, of patients with clinically localized disease (83% of cancers detected), 87% underwent radical prostatectomy, 11% opted for radiation therapy and 2% opted for watchful waiting. Cancers found in the first biopsy group were more multifocal (p = 0.01) while cancers found on second biopsy were more located in the apical-dorsal region (p = 0.003). No significant differences were noted with respect to extracapsular extension, seminal vesical invasion, positive margins, final pathological stage, Gleason score, percentage Gleason grade 4/5, serum PSA and patient age between first and second biopsy. CONCLUSIONS: With an octant biopsy regime, biochemical and pathological features of cancers detected on initial and repeat biopsy in the PSA range 2.0 to 4 ng/ml are comparable in terms of PSA, grade, stage and cancer volume suggesting identical cancer characteristics, thus advocating for a repeat prostate biopsy in case of a negative finding on initial biopsy.     

Prostate volume as an independent predictor of prostate cancer in men with PSA of 10–50?ng ml?1

Prostate volume (PV) has been shown to be associated with prostate cancer (PCa) detection rates in men with a prostate-specific antigen (PSA) in the ‘grey zone'' (2.0–10.0 ng ml⁻¹). However, the PSA ‘grey zone'' in Asian men should be higher because the incidence of PCa in Asian men is relatively low. Therefore, we evaluated the association between PV and PCa detection rates in men with PSAs measuring 10–50 ng ml⁻¹. Men who underwent a 13-core prostatic biopsy with PV documentation participated in the study. A multivariate stepwise regression was used to evaluate whether the PV at time of prostate biopsy could predict the risk of PCa. The rates of PCa among men in different PSA ranges, stratified by PV medians (<60 and ≥60 ml), were calculated. There were 261 men included in the final analysis. PV was the strongest predictor of PCa risk (odds ratio, 0.02; P<0.001) compared to other variables. The PCa rates in men with PVs measuring <60 and ≥60 ml in the 10–19.9 ng ml⁻¹ PSA group were 40.6% and 15.1%, respectively, while the rates for men with PSAs measuring 20–50 ng ml⁻¹ were 65.1% and 26.8%. PV is an independent predictor of PCa in men with PSA measuring 10–50 ng ml⁻¹. In clinical practice, particularly for those countries with lower incidences of PCa, PV should be considered when counselling patients with PSAs measuring 10–50 ng ml⁻¹ regarding their PCa risks.     

A Genetic Score Can Identify Men at High Risk for Prostate Cancer Among Men With Prostate-Specific Antigen of 1–3 ng/ml

Background

The diagnostic performance of a genetic score based on single nucleotide polymorphisms (SNPs) is unknown in the prostate-specific antigen (PSA) range of 1–3 ng/ml. A substantial proportion of men in this PSA span have prostate cancer (PCa), but biomarkers to determine who should undergo a prostate biopsy are lacking.

Objective

To evaluate whether a genetic risk score identifies men in the PSA range of 1–3 ng/ml who are at higher risk for PCa.

Design, setting, and participants

Men aged 50–69 yr with PSA 1–3 ng/ml and without a previous prostate biopsy were selected from the STHLM2 cohort. Of 2696 men, 49 SNPs were genotyped, and a polygenic risk score was calculated. Of these men, 860 were invited according to risk score, and 172 underwent biopsy.

Outcome measurements and statistical analysis

The risk of PCa was assessed using univariate and multivariate logistic regression analysis.

Results and limitations

PCa was diagnosed in 47 of 172 participants (27%), with Gleason sum 6 in 36 of 47 men (77%) and Gleason sum ≥7 in 10 of 47 men (21%); one man had intraductal cancer. The genetic score was a significant predictor of a positive biopsy (p = 0.028), even after adjusting for PSA, ratio of free to total PSA, prostate volume, age, and family history. There was an increase in the odds ratio of 1.60 (95% confidence interval, 1.05–2.45) with increasing genetic risk score. The absolute risk difference of positive biopsy was 19 percentage points, comparing the high and low genetic risk group (37% vs 18%).

Conclusions

A risk score based on SNPs predicts biopsy outcome in previously unbiopsied men with PSA 1–3 ng/ml. Introducing a genetic-based risk stratification tool can increase the proportion of men being classified in line with their true risk of PCa.     

Serum Isoform [−2]proPSA Derivatives Significantly Improve Prediction of Prostate Cancer at Initial Biopsy in a Total PSA Range of 2–10 ng/ml: A Multicentric European Study

Background

Strategies to reduce prostate-specific antigen (PSA)–driven prostate cancer (PCa) overdiagnosis and overtreatment seem to be necessary.

Objective

To test the accuracy of serum isoform [−2]proPSA (p2PSA) and its derivatives, percentage of p2PSA to free PSA (fPSA; %p2PSA) and the Prostate Health Index (PHI)—called index tests—in discriminating between patients with and without PCa.

Design, setting, and participants

This was an observational, prospective cohort study of patients from five European urologic centers with a total PSA (tPSA) range of 2–10 ng/ml who were subjected to initial prostate biopsy for suspected PCa.

Outcome measurements and statistical analysis

The primary end point was to evaluate the specificity, sensitivity, and diagnostic accuracy of index tests in determining the presence of PCa at prostate biopsy in comparison to tPSA, fPSA, and percentage of fPSA to tPSA (%fPSA) (standard tests) and the number of prostate biopsies that could be spared using these tests. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision curve analysis.

Results and limitations

Of >646 patients, PCa was diagnosed in 264 (40.1%). Median tPSA (5.7 vs 5.8 ng/ml; p = 0.942) and p2PSA (15.0 vs 14.7 pg/ml) did not differ between groups; conversely, median fPSA (0.7 vs 1 ng/ml; p < 0.001), %fPSA (0.14 vs 0.17; p < 0.001), %p2PSA (2.1 vs 1.6; p < 0.001), and PHI (48.2 vs 38; p < 0.001) did differ significantly between men with and without PCa. In multivariable logistic regression models, p2PSA, %p2PSA, and PHI significantly increased the accuracy of the base multivariable model by 6.4%, 5.6%, and 6.4%, respectively (all p < 0.001). At a PHI cut-off of 27.6, a total of 100 (15.5%) biopsies could have been avoided. The main limitation is that cases were selected on the basis of their initial tPSA values.

Conclusions

In patients with a tPSA range of 2–10 ng/ml, %p2PSA and PHI are the strongest predictors of PCa at initial biopsy and are significantly more accurate than tPSA and %fPSA.

Trial registration

The study is registered at http://www.controlled-trials.com, ref. ISRCTN04707454.     

Is free/total PSA predictive of pathological stage and Gleason score in patients with prostate cancer and serum PSA<or=10 ng/ml?

INTRODUCTION: To evaluate whether percent free prostate-specific antigen (%-fPSA) could be predictive of pathological stage and Gleason score in patients with prostate cancer (PCa) and serum PSA of 10 ng/ml or less. MATERIALS AND METHODS: In 100 patients with total PSA7 were compared. RESULTS: 32 patients had an organ-confined and 68 a locally advanced PCa. Median %-fPSA level was 15%; Gleasonscore was <7 in 49 patients, equal to 7 in 40 and >7 in 11. Median %-fPSA levels in PCa with Gleason score7 was 14, 15.5 and 15%, respectively. Multiple logistic regression analysis did not show any correlation between %-fPSA in organ-confined vs. non-organ-confined PCa (p=0.4991) either between Gleason score<7 vs. equal to 7 (p=0.588) or >7 (p=0.547). CONCLUSIONS: %-fPSA cut-off does not seem to be useful for preoperative staging of patients with PCa and serum PSA相似文献   

A longitudinal study of PSA and its influential factors in a cohort of Chinese men with initial PSA levels less than 4?ng ml?1

To evaluate the longitudinal change in prostate-specific antigen (PSA) and the influence of initial PSA on the PSA change. We retrospectively analysed health examination data collected at Beijing Hospital from March 2007 to November 2011. Men with an initial PSA levels less than 4 ng ml⁻¹ and an annual PSA test for 5 years were enrolled into the study. The men were separated into four groups by the initial PSA level (0–0.99, 1–1.99, 2–2.99 and 3–3.99 ng ml⁻¹), and the difference in PSA change among the four groups was analysed. A total of 1330 men were enrolled into the study. The mean age, initial PSA and PSA velocity (PSAV) were 58.17±14.63 (range 24–91) years, 1.18±0.79 (range 0–4) ng ml⁻¹ and 0.04±0.25 (range −1.34–2.02) ng ml⁻¹ year⁻¹. Pearson''s correlation analysis showed no correlation between initial PSA and PSAV (r=−0.036, P=0.189). The PSAV of the 0–0.99, 1–1.99, 2–2.99 and 3–3.99 ng ml⁻¹ initial PSA groups was 0.03±0.11, 0.07±0.32, 0.03±0.34 and −0.01±0.43 ng ml⁻¹ year⁻¹, respectively (P=0.06). As the initial PSA increased, the percentage of having a PSAV over 0.75 ng ml⁻¹ year⁻¹ and a negative PSAV both significantly increased. Males with a baseline PSA of 0–0.99, 1–1.99, 2–2.99 and 3–3.99 ng ml⁻¹ had a 1.88%, 6.16%, 16.30% and 57.81% chance, respectively, that their PSA would increase above 4.0 ng ml⁻¹ over the following 4 years (P<0.0001). The PSAV has no correlation with the initial PSA level. However, as the initial PSA increases, the chance that males will have an abnormal PSA or PSAV in the future increases.     

Reasonable Delay of Surgical Treatment in Men with Localized Prostate Cancer - Impact on Prognosis?

PURPOSE: In many centers patients with clinically localized prostate cancer might be confronted with a delay in therapy due to not immediately available treatment capacity at that specific center. Furthermore, a growing amount of patients want to have a second or third opinion before they finally decide what therapeutic option to choose. We investigated whether a reasonable delay from diagnosis to definitive treatment impact recurrence free survival rates in men undergoing radical prostatectomy (RP) for localized prostate cancer. MATERIAL AND METHODS: Preoperative data of 795 men treated for localized prostate cancer by RP between 1/1992 and 6/2000 were evaluated including pretreatment PSA, clinical stage and biopsy Gleason score. In addition, time from biopsy to the date of RP was obtained and investigated as a potential prognostic factor. The influence of the time gap between biopsy and surgery was statistically evaluated by univariate Cox regression analyses and Kaplan-Meier analyses; a multivariate Cox Modell was performed including all preoperative parameters. Relapse following RP was defined as a postoperative PSA level >0.1 ng/ml. RESULTS: Mean followup of the patients was 33 months (1-116 months). Twenty-five percent of the patients failed during that time period. Mean time gap between diagnosis and treatment was 62 days (median 54 days) ranging from 5 to 518 days. Univariate Cox regression analysis showed no significant correlation (p=0.062) of waiting time with recurrence rate. Multivariate Cox regression documented a highly significant association of PSA (p<0.001), clinical stage (p=0.001) and biopsy Gleason grade (p<0.001) but not not for time to treatment (p=0.841). In patients with high-grade cancer again no significant impact of treatment delay was found. CONCLUSION: Treatment delay in the investigated time span of a few months did not adversely affect recurrence free survival rates. Patients can be reassured that they can evaluate treatment options without compromising efficacy due to a delay in treatment.     

Role of Quality of Life in Men with Metastatic Hormone-Refractory Prostate Cancer: How Does Atrasentan Influence Quality of Life?

OBJECTIVE: Progression of hormone-refractory prostate cancer (HRPC) is associated with skeletal complications and bone pain, which contribute to deterioration in quality of life (QOL). The effects of new HRPC therapies on patients' QOL need to be studied. Patient-based assessments that help quantify the risk-benefit profile of HRPC therapies are warranted. This review summarizes the known QOL literature and estimates the potential effect of atrasentan, a novel, selective endothelin A receptor antagonist (SERA), on the QOL of HRPC patients. METHODS: Published studies were identified through a structured, detailed literature review. Clinical studies that report QOL data were reviewed, along with recent QOL data from atrasentan studies. RESULTS: HRPC studies have begun to use QOL assessments as primary endpoints, but different assessments and therapies are not comparable. Very few data integrate QOL with clinical endpoints. Atrasentan clinical trials demonstrated a statistically significant difference in the prostate cancer-specific QOL in favor of atrasentan (p=.032) and an increased quality-adjusted time to progression in men with HRPC. CONCLUSIONS: Atrasentan provides QOL benefits relevant to HRPC. The quality-adjusted analyses applied in the atrasentan studies have begun to lay the foundation for interpreting clinical endpoints in conjunction with QOL. These analyses will facilitate better QOL comparisons within studies and across trials. Further evaluation of atrasentan in HRPC is warranted.     

The role of free to total PSA ratio in prediction of extracapsular tumor extension and biochemical recurrence after radical prostatectomy in patients with PSA between 4 and 10?ng/ml

Objectives

The prognostic value of free to total PSA ratio (F/T PSA) in patients eligible for radical prostatectomy (RP) is controversial. The aim of the present study was to evaluate correlation of F/T PSA with tumor extracapsular extension (ECE) and biochemical recurrence (BR) at long-term follow-up.

Patient and methods

Clinical and pathological data were prospectively gathered from 200 patients treated with RP for clinically localized prostate cancer (PCa) and PSA between 4 and 10?ng/mL. Correlations of preoperative variables including F/T PSA with ECE and BR were evaluated with uni- and multivariate analysis. Adjunctive analyses evaluated the association of PSA F/T with other pathological results. The relationship between preoperative F/T PSA and BR was also assessed with Kaplan?CMeier survival analysis.

Results

Lower F/T PSA was significantly correlated with ECE (p?=?0.0063), higher GS (p?=?0.0054), and seminal vesicles involvement (p?=?0.0047). The F/T PSA value of 14% provided the greatest discrimination in predicting ECE. At multivariate analysis, F/T PSA did not achieve the statistical significance for predicting ECE independently. At a mean (median, range) follow-up of 52 (48, 14?C116) months, preoperative F/T PSA resulted significantly correlated with BR (p?=?0.001). At the Kaplan?CMeier survival analysis, the 5-year BR free survival rate resulted 89.3 and 68.9% in the group with F/T PSA?>14 and ??14?ng/mL, respectively (log rank p?=?0.0022). At Cox proportional hazard model, only ECE resulted an independent predictor of BR (R?=?2.646, p?=?0.037).

Conclusion

In patients with clinically localized PCa and PSA 4?C10?ng/ml, lower F/T PSA was significantly associated with ECE, other adverse pathologic features, and with BR at the long-term follow-up, but only ECE resulted an independent predictor of BR in our series.     

血清PSA〈4．0ng/ml的人群中前列腺癌集团筛查的病理学特征

目的探讨血清PSA<4.0ng/ml的人群中前列腺癌的病理学特征。方法对长春市15192名男性进行血清前列腺特异性抗原(PSA)检测,其中46名血清PSA<4.0ng/ml伴有直肠指诊检查异常者接受了经直肠超声引导下前列腺6点活检穿刺,并应用组织病理学、免疫组织化学及统计学等方法进行系统的病理学研究和分析。结果(1)血清PSA<4.0ng/ml者有13886名,46人进行了前列腺活检穿刺,活检率为0.33%(46/13886)。(2)46名男性血清PSA值在0.03～3.84ng/ml之间,主要分布在0～1.9ng/ml间,占60.9%。(3)46例前列腺活检病理诊断:良性前列腺增生29例,占63.1%;前列腺癌10例,占21.7%;炎症性病变与肉瘤各3例,分别占6.5%;转移癌1例占2.2%。10例血清PSA<4.0ng/ml的前列腺癌中普通型腺癌5例,以中分化(3/5)、器官内癌(4/5)为主,且血清PSA值较靠近4ng/ml;特殊类型前列腺癌5例,占50%,均为进展期癌,血清PSA值相对较低。结论(1)血清PSA<4.0ng/ml的人群中有前列腺癌存在。(2)血清PSA<4.0ng/ml的人群中前列腺癌以中分化器官内腺癌和特殊类型进展期前列腺癌为主。(3)应用直肠指诊检查(DRE)能检出血清PSA<4.0ng/ml的前列腺癌,且检出率与血清PSA值成正相关,两者联合应用可以提高前列腺癌的检出率。