18F-fluciclovine PET CT detection of biochemical recurrent prostate cancer at specific PSA thresholds after definitive treatment

ObjectivesTo evaluate various Prostate-Specific Antigen (PSA) thresholds at which a ¹⁸F-fluciclovine PET scan could be considered in the setting of biochemical recurrent prostate cancer after definitive treatment.MethodsWe analyzed available records of men who underwent a ¹⁸F-fluciclovine PET scan after definitive therapy at a single academic institution between November 2016 to May 2018. The primary outcome was the rate of positive imaging findings at specific PSA thresholds. We then employed empiric strategies including a ROC curve and decision curve analysis to identify a specific threshold for which obtaining a positive result would be optimized.ResultsA total of 115 men underwent imaging with ¹⁸F-fluciclovine PET. No concerning lesions were identified in 25 (21.7%) patients, 32 (27.8%) had a solitary lesion identified, 45 (39.1%) had 2 to 5 lesions, and 13 (11.3%) had greater than 5 suspicious lesions identified. At PSA thresholds of less than 0.5, 0.5 to 2.0, and greater than 2, lesions were detected in 55.5% (12/22), 70.6% (24/34), and 91.5% (54/59) of patients respectively [P < 0.001]. Our ROC analysis yielded a PSA threshold of 2.10 while our decision curve analysis provided a PSA cutoff of 1.38.ConclusionThis study constitutes an early single institution series evaluating the use of ¹⁸F-fluciclovine PET scans in the assessment of biochemically recurrent prostate cancer after definitive treatment. The probability of having positive imaging findings and increasing numbers of suspicious lesions rises with increasing PSA. Utilization of a lower PSA threshold of 0.5 may allow earlier intervention with salvage therapies in biochemical recurrence. However, using a threshold below 1 carries a higher risk of negative scans. Employing a higher PSA threshold of 1 to 2 carries greater sensitivity and specificity and may maximize identifying individuals with early BCR who may benefit from early intervention, while minimizing negative scans.     

Early detection of prostate cancer local recurrence by urinary prostate-specific antigen

Purpose:

We assessed the role of urinary prostate-specific antigen (uPSA) in the follow-up of prostate cancer after retropubic radical prostatectomy (RRP) for the early detection of local recurrences.

Methods:

We recruited 50 patients previously treated for prostate cancer with RRP and who had not experienced a prostate-specific antigen (PSA) recurrence within their first postoperative year into a cross-sectional laboratory assessment and prospective 6-year longitudinal follow-up study. We defined biochemical failure as a serum PSA (sPSA) of 0.3 μg/L or greater. Patients provided blood samples and a 50-mL sample of first-voided urine. We performed Wilcoxon rank-sum and Fisher exact tests for statistical analysis.

Results:

The median sPSA was 0.13 μg/L. The median uPSA was 0.8 μg/L, and was not significantly different when comparing Gleason scores or pathological stages. Of the 50 patients, 27 initially had a nondetectable sPSA but a detectable uPSA, and 11 patients experienced sPSA failure after 6 years. Six patients had detectable sPSA and uPSA initially. Fifteen patients were negative for both sPSA and uPSA, and 13 remained sPSA-free after 6 years. The odds ratio (OR) of having sPSA failure given a positive uPSA test was 4.5 if sPSA was undetectable, but was reduced to 2.6 if sPSA was detectable. The pooled Mantel–Haenszel OR of 4.2 suggested that a detectable uPSA quadrupled the risk of recurrence, independent of whether sPSA was elevated or not. The sensitivity of uPSA for detecting future sPSA recurrences was 81% and specificity was 45%.

Conclusion:

Urinary PSA could contribute to an early detection of local recurrences of prostate cancer after a radical prostatectomy.     

C-reactive protein is significantly associated with prostate-specific antigen and metastatic disease in prostate cancer

OBJECTIVE: To further analyse the relationship of c-reactive protein (CRP) levels to prostate cancer, by measuring CRP in men with prostate cancer and benign prostatic hypertrophy (BPH), as chronic inflammation has long been linked to cancers with an infectious cause and CRP is a nonspecific marker for inflammation, associated with prostate cancer incidence and progression. PATIENTS AND METHODS: Data from 114 men, most of whom had had radioactive seeds implanted, were evaluated from November 1990 to April 2002. In addition, 27 men were included who had biopsy-confirmed BPH. CRP was assessed with an automated chemiluminometric high-sensitivity assay kit. RESULTS: There was no significant difference in CRP levels in men with localized prostate cancer or BPH but levels were significantly higher in men with bone metastases. There was also a significant correlation of CRP level with prostate-specific antigen (PSA) in those with cancer. Because PSA is correlated with disease stage, multiple linear regression was used with CRP as the dependent variable, and PSA and disease stage as independent variables. The regression was significant overall (P < 0.001) and the effect of disease stage on CRP (P < 0.001) was independent of the effect of PSA level (P = 0.001). CONCLUSION: The strong association of CRP with PSA, independent of tumour stage, suggests that inflammation might be fundamental in prostate cancer, and that chronic inflammation may be a legitimate target for prostate cancer chemoprevention and treatment.     

Systemic inflammatory response, prostate-specific antigen and survival in patients with metastatic prostate cancer

BACKGROUND: It is increasingly recognised that, in cancer patients, disease progression is dependent on a complex interaction of the tumour and the host inflammatory response and that the systemic inflammatory response, as evidenced by an elevated C-reactive protein (CRP) concentration, may be a useful prognostic factor. MATERIALS AND METHODS: The prognostic value of CRP compared with prostate-specific antigen (PSA) was examined in 62 patients with metastatic prostate cancer receiving androgen-deprivation therapy. RESULTS: In all, 41 (66%) of patients died, 38 (61%) of their disease. On univariate survival analysis, PSA (p < 0.05) and CRP (p < 0.05) were significant predictors of cancer-specific survival. On multivariate analysis, both PSA (HR 1.96, 95% CI 1.00-3.83, p = 0.049) and CR (HR 1.97, 95% CI 0.99-3.92, p = 0.052) were independent predictors of cancer-specific survival. PSA concentrations were significantly correlated with those of CRP (r(s) = 0.46, p < 0.001). CONCLUSION: The results of the present study suggest that, in patients with metastatic prostate cancer, the presence of an elevated CRP concentration predicts poor outcome, independent of PSA.     

Use of hormonal therapy in men with metastatic prostate cancer

PURPOSE: Bilateral orchiectomy or luteinizing hormone releasing hormone agonists represent the standard of care for metastatic prostate cancer. In this population based study we assessed the use rates of these therapies in men who died of prostate cancer. MATERIAL AND METHODS: A total of 9,110 men 65 years or older who died of prostate cancer in 1991 to 2000 were identified through the population based Surveillance, Epidemiology and End Results, and Medicare linked database to determine hormonal therapy use rates. A modified Poisson regression model was used to estimate the adjusted effects of various factors associated with hormone use. RESULTS: Approximately 38% of black and 25% of white men did not receive hormonal therapy before dying of prostate cancer. After adjusting for cancer status at diagnosis and other potential confounding factors black race and residence in low income areas were associated with lower hormonal therapy use (relative risk 0.73, 95% CI 0.67 to 0.80 and 0.91, 95% CI 0.85 to 0.98, respectively). Hormonal therapy use was most comprehensive in the Northeast. CONCLUSIONS: A substantial number of men who die as a consequence of prostate cancer never receive hormonal therapy. The use of hormonal therapy varies significantly. Further studies are warranted to determine factors that may be associated with the incomplete use of hormonal therapy for metastatic prostate cancer.     

Antibacterial therapy improves the effectiveness of prostate cancer detection using prostate-specific antigen in patients with asymptomatic prostatitis

Objectives  

To improve prostate cancer (PC) detection accuracy among patients with a prostate-specific antigen (PSA) above 4.0 ng/ml and asymptomatic prostate inflammation.     

The role of free prostate-specific antigen in prostate cancer detection

Prostate-specific antigen (PSA) is the most important serum tumor marker for prostate cancer detection. Free PSA is one of the many molecular forms of PSA that have been identified. Percent free PSA improves the specificity (elimination of unnecessary biopsies) for prostate cancer detection in men with nonsuspicious digital prostate examination and total serum PSA ranges between 4 and 10 ng/ mL. Further study is necessary to determine the optimal clinical utility of percent free PSA in men with a total serum PSA level of less than 4 ng/mL. In addition, the level of free PSA may be affected by many factors, including age, prostate volume, prostate manipulation, sample handling, and type of assay used.     

前列腺根治术后是否需要立即给予内分泌治疗值得商榷

前列腺癌根治术后生化复发患者的治疗选择目前还有一些争议,可供选择的治疗方法包括：等待观察、挽救性放疗、内分泌治疗（包括全雄激素阻断、间歇性内分泌治疗、抗雄激素药物单药治疗、抗雄激素药物联合5a-还原酶抑制剂等）。经过对患者全面评估后,首先应该判断患者是肿瘤局部复发还是远处转移。局部复发可能性大者可选用等待观察或挽救性放疗,远处转移可能性大者可选用内分泌治疗。     

An algorithm for prostate cancer detection in a patient population using prostate-specific antigen and prostate-specific antigen density

Summary Prostate-specific antigen (PSA) is the most accurate serum marker for cancer of the prostate (CaP). However, its sensitivity and specificity are suboptimal, especially at values ranging between 4.1 and 10.0 ng/ml (monoclonal), because benign prostatic hypertrophy and hyperplasia (BPH) and CaP frequently coexist in this range. This study was undertaken to determine the value of incorporating prostate volume measurements with serum PSA levels in a quotient (PSA/volume) entitled PSA density (PSAD). A total of 3140 patients were analyzed and stratified by serum PSA, digital rectal examination (DRE), transrectal prostate ultrasound (TRUS), TRUS volume determination and PSAD. All patients were referred for evaluation and therefore do not represent a screened population. Patients underwent prostate biopsies when abnormalities in TRUS or DRE were detected. Although both PSA and PSAD have statistical significance when the serum PSA value is 4.0 ng/ml, neither has clinical significance in differentiating BPH from CaP. At serum levels ranging between 4.1 and 10.0 ng/ml, PSA has no ability to differentiate BPH from CaP, whereas PSAD does so with statistical and clinical significance. When the PSA value is between 10.1 and 20.0 ng/ml, only PSAD is statistically significant. When PSA exceeds 20 ng/ml, PSAD is redundant. We conclude that all patients with an abnormality on DRE or TRUS should undergo prostate biopsy. If the PSA value is 4.0 ng/ml, TRUS and PSAD are not warranted and routine biopsy is not recommended. For intermediate PSA levels, 4.1–10.0 ng/ml, TRUS, TRUS prostate volume, and PSAD are important. The use of PSAD provides unique information regarding the need for biopsy and the likelihood of CaP. At PSA levels ranging between 10.1 and 20.0 ng/ml, PSAD will identify those patients who are less likely to have CaP, but all should undergo biopsy. If the PSA value is >20 ng/ml, all patients should undergo a biopsy.     

Early versus delayed hormonal therapy for prostate specific antigen only recurrence of prostate cancer after radical prostatectomy

PURPOSE: Hormonal therapy (HT) is the current mainstay of systemic treatment for prostate specific antigen (PSA) only recurrence (PSAR), however, there is virtually no published literature comparing HT to observation in the clinical setting. The goal of this study was to examine the Department of Defense Center for Prostate Disease Research observational database to compare clinical outcomes in men who experienced PSAR after radical prostatectomy by early versus delayed use of HT and by a risk stratified approach. MATERIALS AND METHODS: Of 5382 men in the database who underwent primary radical prostatectomy (RP), 4967 patients were treated in the PSA-era between 1988 and December 2002. Of those patients 1352 men who had PSAR (PSA after surgery greater than 0.2 ng/ml) and had postoperative followup greater than 6 months were used as the study cohort. These patients were further divided into an early HT group in which patients (355) received HT after PSA only recurrence but before clinical metastasis and a late HT group for patients (997) who received no HT before clinical metastasis or by current followup. The primary end point was the development of clinical metastases. Of the 1352 patients with PSAR clinical metastases developed in 103 (7.6%). Patients were also stratified by surgical Gleason sum, PSA doubling time and timing of recurrence. Univariate and multivariate Cox proportional hazard models were used to evaluate the effect of early and late HT on clinical outcome. RESULTS: Early HT was associated with delayed clinical metastasis in patients with a pathological Gleason sum greater than 7 or PSA doubling time of 12 months or less (Hazards ratio = 2.12, p = 0.01). However, in the overall cohort early HT did not impact clinical metastases. Race, age at RP and PSA at diagnosis had no effect on metastasis-free survival (p >0.05). CONCLUSIONS: The retrospective observational multicenter database analysis demonstrated that early HT administered for PSAR after prior RP was an independent predictor of delayed clinical metastases only for high-risk cases at the current followup. Further study with longer followup and randomized trials are needed to address this important issue.     

The role of prostate-specific antigen velocity in prostate cancer early detection

Prostate-specific antigen velocity (PSAV) is the rate of change in prostate-specific antigen (PSA) values with repeated measurement over time. Accurate use of PSAV for prostate cancer early detection requires the use of two or more PSA levels collected over approximately 1.5 to 2 years. When these specimen collection criteria are met, more than 95% of men without prostate cancer will have a PSAV less than 0.75 ng/mL/y, whereas approximately 70% of men with prostate cancer will have a PSAV above this threshold. PSAV is thus more specific than routine PSA testing for the presence of prostate cancer, because few men (< 5%) without prostate cancer have a PSAV sufficient to trigger prostate biopsy. The use of PSAV in the increasing number of men with lengthy PSA histories obtained in systematic efforts at prostate cancer early detection may aid in diagnosing prostate cancer and spare some men unnecessary prostate biopsy. This review briefly summarizes the theoretic basis and clinical utility of PSAV in prostate cancer early detection.     

Evaluation of precursor prostate-specific antigen isoform ratios in the detection of prostate cancer

OBJECTIVE: Disease-associated isoforms of the prostate-specific antigen (PSA) have recently been identified. We evaluated the efficacy of using precursor isoforms of PSA (pPSA) and their ratios for the detection of prostate cancer. METHODS: Serum concentrations of [-2], [-4], and [-7]pPSA, BPSA, and free PSA (fPSA) were retrospectively measured in 43 selected men. Of the 43 men, 15 had clinical T2 prostate cancer with ultrasound-estimated prostate volumes (PVs) of >50 cm(3), 13 had clinical T2 prostate cancer with (PVs) <25 cm(3), and 15 were prostate cancer-free with PV >50 cm(3). We calculated sum pPSA ([-2]+[-4]+[-7]pPSA). We also compared the ratios of: free/total PSA, [-2]pPSA/fPSA, [-2]pPSA/BPSA, [-2]pPSA/(fPSA-BPSA), [-2]pPSA/(fPSA-sum pPSA), and [-2]pPSA/{fPSA-(sum pPSA+BPSA)} among these three groups. RESULTS: The median [-2]pPSA/(fPSA-sum pPSA) ratio was significantly higher in men with prostate cancer with or without large PV compared with men with large PV without prostate cancer. Values for median [-2]pPSA/free PSA ratio were higher in men with prostate cancer with or without large PV compared with men with large PV, and without prostate cancer, but the differences were not statistically significant. CONCLUSIONS: In this preliminary study, [-2]pPSA/(fPSA-sum pPSA) ratio was not associated with prostate gland volume but was associated with prostate cancer. This ratio may be useful in the detection of prostate cancer, particularly in men with larger glands.