Prostate Specific Antigen Density Versus Prostate Specific Antigen Slope as Predictors of Prostate Cancer in Men with Initially Negative Prostatic Biopsies

Purpose

We determined if prostate specific antigen (PSA) density and PSA slope alone or in combination could be used to predict which men with persistently elevated serum PSA and prior negative prostate biopsies will have prostate cancer on repeat evaluation.

Materials and Methods

In our PSA-1 data base we identified 327 men 50 years old or older with an initially negative prostate biopsy who had persistent PSA elevation, and compared those who did and did not have prostate cancer on subsequent serial prostatic biopsy.

Results

Of 70 men with a PSA density of 0.15 or more and PSA slope of 0.75 ng./ml. or more annually compared to 83 with a PSA density of less than 0.15 and PSA slope of less than 0.75 ng./ml. annually 32 (46 percent) and only 11 (13 percent), respectively, had prostate cancer on subsequent prostate biopsies (p less than 0.0001). In a hierarchical logistic regression analysis PSA density and PSA slope were predictive of prostate cancer on subsequent biopsy (p = 0.001 and 0.03, respectively). PSA density of 0.15 or more alone or PSA slope of 0.75 ng./ml. or more annually alone as the indicator for repeat biopsy would have missed 35 and 40 percent of cancers, respectively.

Conclusions

In men with persistently elevated serum PSA after an initially negative prostate biopsy, PSA density and PSA slope alone or in combination provide useful predictive information about the results of repeat prostate biopsies. However, these parameters are not sufficiently sensitive to identify all patients with detectable prostate cancer.     

Serum Pro Prostate Specific Antigen Improves Cancer Detection Compared to Free and Complexed Prostate Specific Antigen in Men With Prostate Specific Antigen 2 to 4 Ng/Ml

PurposePro prostate specific antigen (pPSA) is a precursor form of PSA enriched in tumor compared to benign prostate tissues that may be a more specific serum marker for prostate cancer. Serum pPSA was measured in the clinically relevant early detection PSA range of 2 to 10 ng/ml.Materials and MethodsResearch use immunoassays were used to measure native and truncated forms of pPSA. The subject cohort contained 1,091 serum specimens from men enrolled in prostate cancer screening studies at 2 sites who had undergone prostate biopsy and were divided into PSA ranges of 2 to 4 ng/ml (benign 320, cancer 235) and 4 to 10 ng/ml (benign 315, cancer 221).ResultsIn PSA ranges 2 to 4, 2 to 6, 4 to 10 and 2 to 10 ng/ml, pPSA in a ratio with free PSA (%pPSA) gave the highest cancer specificity. At 2 to 4 ng/ml and 90% sensitivity, %pPSA spared 19% of unnecessary biopsies compared to 10% for free PSA and 11% for complexed PSA(p <0.001). Similar results were obtained at PSA 2 to 6 ng/ml. At 90% sensitivity in the PSA 4 to 10 ng/ml range, %pPSA spared 31% of unnecessary biopsies compared to 20% for % free PSA and 19% for complexed PSA (p <0.0001). In the combined 2 to 10 ng/ml range, %pPSA spared 21% of unnecessary biopsies compared to 13% for % free PSA and 9% for complexed PSA (p <0.0001).ConclusionsThe %pPSA significantly improved specificity for cancer detection and decreased the number of unnecessary biopsies in the PSA 2 to 4 ng/ml range. This relative improvement of %pPSA compared to % free PSA and complexed PSA was maintained throughout the PSA range of 2 to 10 ng/ml.     

Long-term Continence Outcomes in Men Undergoing Radical Prostatectomy for Clinically Localized Prostate Cancer

Background

Urinary incontinence is a common short-term complication of radical prostatectomy (RP). Little is known about the long-term impact of RP on continence.

Objective

To elucidate the long-term progression of continence after RP.

Design, setting, and participants

From October 2000 through September 2012, 1788 men undergoing open RP for clinically localized prostate cancer by a single surgeon at an urban tertiary care center prospectively signed consent to be followed before RP and at 3, 6, 12, 24, 96, and 120 mo after RP. A consecutive sampling method was used and all men were included in this study.

Intervention

Men underwent open RP.

Outcome measurements and statistical analysis

Regression models controlled for preoperative University of California, Los Angeles–Prostate Cancer Index urinary function score (UCLA-PCI-UFS), age, prostate-specific antigen level, Gleason score, stage, nerve-sparing status, race, and marital status were used to evaluate the association of time since RP with two dependent variables: UCLA-PCI-UFS and continence status.

Results and limitation

The mean UCLA-PCI-UFS declined between 2 yr and 8 yr (83.8 vs 81.8; p = 0.007) and marginally between 8 yr and 10 yr (81.8 vs 79.6; p = 0.036) after RP, whereas continence rate did not significantly change during these intervals. Men ≥60 yr old experienced a decline in mean UCLA-PCI-UFS between 2 yr and 8 yr (p = 0.002) and a marginal decline in continence rate between 2 yr and 10 yr (p = 0.047), whereas these variables did not change significantly in men <60 yr old. These outcomes are for an experienced surgeon, so caution should be exercised in generalizing these results.

Conclusions

Between 2 yr and 10 yr after RP, there were slight decreases in mean UCLA-PCI-UFS and continence rates in this study. Men aged <60 yr had better long-term outcomes. These results provide realistic long-term continence expectations for men undergoing RP.     

Prostate Specific Antigen Regression and Progression after Androgen Deprivation for Localized and Metastatic Prostate Cancer

To identify prostate specific antigen (PSA) functions of prognostic significance in regard to treatment with androgen deprivation for prostate cancer we analyzed the pretreatment PSA, PSA half-life, PSA nadirs, times to PSA elevation and PSA doubling times in 245 patients with localized and 78 with metastatic disease who were treated with this modality. There was a direct correlation between the pretreatment PSA and the time to PSA elevation in patients with localized cancer (p = 0.000003) but no significant correlation in those with metastatic cancer. The PSA half-life was highly variable and did not correlate with other PSA functions of prognostic significance. Incremental increases in the PSA nadir correlated with the time to PSA elevation in patients with localized and metastatic cancer (p less than 0.000001 and p = 0.00009, respectively), and with other parameters of prognostic significance. The median PSA doubling time in 26 patients with localized cancer in whom distant metastases did not develop (7.5 months) was significantly longer than that in 7 in whom new metastases developed (2.5 months) and in 43 with preexisting metastatic cancer (2.5 months) (p less than 0.05 and p less than 0.0001, respectively). In the 7 patients with localized cancer in whom metastases developed the median of the ratios of the PSA when the metastases were manifest and the pretreatment PSA was 0.14, and in 24 patients with preexisting metastatic cancer the median of the ratios of the antemortem PSA and the pretreatment PSA was 1.2. These data show that PSA synthesis by prostate cancer is reduced after androgen deprivation but that the PSA nadir and PSA doubling time following treatment provide important prognostic information.     

比卡鲁胺联合标准化治疗对中国局部前列腺癌患者的治疗效果的评价

目的比较比卡鲁胺联合标准化治疗和单独标准化治疗对治疗中国局部前列腺癌患者的效果。方法 431例前列腺癌患者按照1∶1的比例随机分为单独标准化治疗组(前列腺癌根治术、放疗或等待观察)和联合治疗组。主要观察指标包括无进展生存率和总体生存率。结果中位随访时间为4.3年。两组的总体生存率(hazard ratio 0.87;95%CI 0.58~1.3;P=0.53)和临床无进展生存率(hazard ratio 0.78;95%CI 0.5~1.22;P=0.28)没有明显的统计学差别。联合治疗组的前列腺特异抗原无进展生存率较单独治疗组明显升高(hazard ratio 0.36;95%CI 0.19~0.71;P=0.002)。结论与单独标准化治疗相比,比卡鲁胺联合标准化治疗对于治疗中国局部前列腺癌患者并未表现出明显的优势。     

Radical Prostatectomy or Observation for Clinically Localized Prostate Cancer: Extended Follow-up of the Prostate Cancer Intervention Versus Observation Trial (PIVOT)

BackgroundVery long-term mortality in men with early prostate cancer treated with surgery versus observation is uncertain.ObjectiveTo determine long-term effects of surgery versus observation on all-cause mortality for men with early prostate cancer.Design, setting, and participantsThis study evaluated long-term follow-up of a randomized trial conducted at the US Department of Veterans Affairs and National Cancer Institute sites. The participants were men (n = 731) ≤75 yr of age with localized prostate cancer, prostate-specific antigen (PSA) <50 ng/ml, life expectancy ≥10 yr, and medically fit for surgery.InterventionRadical prostatectomy versus observation.Outcome measurements and statistical analysisAll-cause mortality was assessed in the entire cohort and patient and tumor subgroups. Intention-to-treat analysis was conducted using Kaplan-Meier methods with log-rank tests and Cox proportional hazard models; cumulative mortality incidence, between-group differences, and relative risks were also assessed at predefined time periods.Results and limitationsDuring 22.1 yr (median follow-up for survivors = 18.6 yr; interquartile range: 16.6–20.0), 515 men died; 246 of 346 men (68%) were assigned to surgery versus 269 of 367 (73%) assigned to observation (hazard ratio 0.84 [95% confidence interval {CI}: 0.70–1.00]; p =  0.044 [absolute risk reduction = 5.7 percentage points, 95% CI: –0.89 to 12%]; relative risk: 0.92 [95% CI: 0.84–1.01]). The restricted mean survival in the surgical group was 13.6 yr (95% CI: 12.9–14.3) versus 12.6 yr (95% CI: 11.8–13.3) in the observation group; a mean of 1 life-year was gained with surgery. Results did not significantly vary by patient or tumor characteristics, although differences were larger favoring surgery among men aged <65 yr, of white race, and having better health status, fewer comorbidities, ≥34% positive prostate biopsy cores, and intermediate-risk disease. Results were not adjusted for multiple comparisons, and we could not assess outcomes other than all-cause mortality.ConclusionsSurgery was associated with small very long-term reductions in all-cause mortality and increases in years of life gained. Absolute effects did not vary markedly by patient characteristics. Absolute effects and mean survival were much smaller in men with low-risk disease, but were greater in men with intermediate-risk disease although not in men with high-risk disease.Patient summaryIn this randomized study, we evaluated death from any cause in men with early prostate cancer treated with either surgery or observation. Overall, surgery may provide small very long-term reductions in death from any cause and increases in years of life gained. Absolute effects were much smaller in men with low-risk disease, but were greater in men with intermediate-risk disease although not in men with high-risk disease. Strategies are needed to identify men needing and benefitting from surgery while reducing ineffective treatment and overtreatment.