Ultrasensitive Prostate-specific Antigen Assays Research Articles

Prostate-Specific Antigen as an Ultrasensitive Biomarker for Patients with Early Recurrent Prostate Cancer: How Low Shall We Go? A Systematic Review.

Serum prostate-specific antigen (PSA) needs to be monitored with ultrasensitive PSA assays (uPSAs) for oncologists to be able to start salvage radiotherapy (SRT) while PSA is <0.5 µg/L for patients with prostate cancer (PCa) relapsing after a radical prostatectomy (RP). Our systematic review (SR) aimed to summarize uPSAs for patients with localized PCa. The SR was registered as InPLASY2023110084. We searched for studies on Google Scholar, PUBMED and reference lists of reviews and studies. We only included studies on uPSAs published in English and excluded studies of women, animals, sarcoidosis and reviews. Of the 115 included studies, 39 reported PSA assay methods and 76 reported clinical findings. Of 67,479 patients, 14,965 developed PSA recurrence (PSAR) and 2663 died. Extremely low PSA nadir and early developments of PSA separated PSAR-prone from non-PSAR-prone patients (cumulative p value 3.7 × 1012). RP patients with the lowest post-surgery PSA nadir and patients who had the lowest PSA at SRT had the fewest deaths. In conclusion, PSA for patients with localized PCa in the pre-PSAR phase of PCa is strongly associated with later PSAR and survival. A rising but still exceedingly low PSA at SRT predicts a good 5-year overall survival.

Free/Total Serum Prostate-Specific Antigen Ratio in Women with Colorectal Cancer Has Prognostic Significance.

The presence of prostate-specific antigen (PSA) in colon cancer tissues has been shown, but its clinical significance has not been known yet in colorectal cancer patients. We investigated the prognostic significance of percent free PSA value (free PSA/total PSA×100) in female patients with colorectal cancer. The serum concentrations of total and free PSA were measured by solid-phase two-site immunoradiometric assay in 184 patients. The cancer-specific survival (CSS) of patients with percent free PSA value ≥35 was significantly better compared to that of patients with percent free PSA value <35 (CSS rate was 82.9 and 55.5%, respectively; log-rank x2=8135, p=0.004). In multivariate Cox analysis, this percent free PSA threshold value had independent prognostic significance (relative risk 0.27, 95% confidence interval 0.11-0.64, p=0.003). Percent free PSA value, calculated by serum total and free PSA levels, has prognostic significance in women with colorectal cancer. The studies with larger patient series, utilizing ultrasensitive PSA assays whose lowest detection limit is lower, are required for a clearer understanding of this issue.

Solitary recurrence of castration-resistant prostate cancer with low or undetectable levels of prostate specific antigen salvaged with local ablative radiation therapy: A case report

Prostate cancer recurrences are usually first detected by increased levels of prostate specific antigen (PSA), and systemic therapy is often initiated if distant metastasis is confirmed. However, low or nearly undetectable levels of PSA in the modern era of ultrasensitive PSA assay may be difficult to interpret in patients with a history of prostate cancer. Deciding whether to initiate additional systemic therapy in limited indolent metastatic disease while balancing the quality of life of the patient and ensuring the oncologic control of the disease may be challenging. In the present study, the case of a biopsy-confirmed solitary spine recurrence of prostate cancer with nearly undetectable but persistent levels of PSA (0.05 ng/ml) is reported. Treatment of the recurrence with local ablative radiotherapy improved the pain experienced by the patient, and reduced his levels of PSA to undetectable limits (<0.05 ng/ml). Repeated imaging analysis, PSA assay and clinical assessment demonstrated durable control of the disease without the requirement for additional systemic treatments. The present case highlighted the importance of initiating appropriate work-up according to the clinical scenario. Local treatment for solitary or oligometastatic recurrence of prostate cancer may enhance the effectiveness of current therapeutic strategies and benefit certain patients.

Do Ultrasensitive Prostate Specific Antigen Measurements Have a Role in Predicting Long-Term Biochemical Recurrence-Free Survival in Men after Radical Prostatectomy?

In this study we evaluate an ultrasensitive prostate specific antigen assay in patients with prostate cancer after radical prostatectomy to predict long-term biochemical recurrence-free survival. A total of 754 men who underwent radical prostatectomy and had an undetectable prostate specific antigen after surgery (less than 0.1 ng/ml) were studied. Prostate specific antigen was measured in banked serum specimens with an ultrasensitive assay (Hybritech® PSA, Beckman Coulter Access® 2) using a cutoff of 0.01 ng/ml. Prostate specific antigen was also measured in 44 men after cystoprostatectomy who had no pathological evidence of prostate cancer with the Hybritech assay and with the Quanterix AccuPSA™ assay. Of the 754 men 17% (131) experienced biochemical recurrence (median 4.0 years). Those men without biochemical recurrence (83%, 623) had a minimum of 5 years of followup (median 11). Prostate specific antigen was less than 0.01 ng/ml in 93.4% of men with no biochemical recurrence, whereas 30.5% of men with biochemical recurrence had a prostate specific antigen of 0.01 ng/ml or greater. On multivariate analysis postoperative prostate specific antigen at a 0.01 ng/ml cutoff, pathological stage and Gleason score, and surgical margins were significant independent predictors of biochemical recurrence risk. Kaplan-Meier estimates for mean biochemical recurrence-free survival were 15.2 years (95% CI 14.9-15.6) for prostate specific antigen less than 0.01 ng/ml and 10.0 years (95% CI 8.4-11.5) for prostate specific antigen 0.01 ng/ml or greater (p <0.0001). Biochemical recurrence-free rates 11 years after surgery were 86.1% (95% CI 83.2-89.0) for prostate specific antigen less than 0.01 ng/ml and 48.9% (95% CI 37.5-60.3) for prostate specific antigen 0.01 ng/ml or greater (p <0.0001). Prostate specific antigen concentrations in 44 men after cystoprostatectomy were all less than 0.03 ng/ml, with 95.4% less than 0.01 ng/ml. In men with a serum prostate specific antigen less than 0.1 ng/ml after radical prostatectomy a tenfold lower cutoff (0.01 ng/ml) stratified biochemical recurrence-free survival and was a significant independent predictor of biochemical recurrence, as were pathological features. Prostate specific antigen concentrations in men without pathological evidence of prostate cancer suggest that a higher prostate specific antigen concentration (0.03 ng/ml) in the ultrasensitive range may be needed to define the detection threshold.

Ultra-sensitive protein detection via Single Molecule Arrays towards early stage cancer monitoring

The early diagnosis of cancers and continued monitoring of tumor growth would be greatly facilitated by the development of a blood-based, non-invasive, screening technique for early cancer detection. Current technologies for cancer screening and detection typically rely on imaging techniques or blood tests that are not accurate or sensitive enough to definitively diagnose cancer at its earliest stages or predict biologic outcomes. By utilizing Single Molecule Arrays (SiMoA), an ultra-sensitive enzyme-linked immunosorbent assay (ELISA) technique, we were able to measure increasing levels of prostate specific antigen (PSA) within murine serum over time, which we attribute to tumor development. The measured concentrations of PSA were well below the detectable limits of both a leading clinical diagnostic PSA ELISA assay as well as a commercial ultra-sensitive PSA assay. Our work benchmarks the role of SiMoA as a vital tool in monitoring previously non-detectable protein biomarkers in serum for early cancer detection and offers significant potential as a non-invasive platform for the monitoring of early stage cancer.

Ultrasensitive Prostate Specific Antigen after Prostatectomy Reliably Identifies Patients Requiring Postoperative Radiotherapy

Integrating ultrasensitive prostate specific antigen with surveillance in patients at high risk after radical prostatectomy potentially optimizes treatment by correctly identifying recurrence, promoting an early salvage strategy and minimizing overtreatment. We tested the power of postoperative ultrasensitive prostate specific antigen to identify eventual biochemical failure. We identified 247 patients at high risk with a median followup of 44 months who underwent radical prostatectomy from 1991 to 2013. Each patient had extraprostatic extension and/or a positive margin. Surgical technique, initial prostate specific antigen, pathology findings and postoperative prostate specific antigen were analyzed. The ultrasensitive prostate specific antigen assay threshold was 0.01 ng/ml. Conventional biochemical relapse was defined as prostate specific antigen 0.2 ng/ml or greater. Kaplan-Meier and Cox multivariate analyses were done to compare the rates of ultrasensitive prostate specific antigen recurrence and conventional biochemical relapse. Sensitivity analysis revealed that ultrasensitive prostate specific antigen 0.03 ng/ml or greater was the optimal threshold to identify recurrence. A first postoperative ultrasensitive value of 0.03 ng/ml or greater, Gleason grade, T stage, initial prostate specific antigen and margin status predicted conventional biochemical relapse. On multivariate analysis only a first postoperative ultrasensitive value of 0.03 ng/ml or greater, Gleason grade and T stage independently predicted conventional biochemical relapse. First postoperative ultrasensitive prostate specific antigen 0.03 ng/ml or greater conferred the highest risk (HR 8.5, p < 0.0001) and identified conventional biochemical relapse with greater sensitivity than undetectable first conventional prostate specific antigen (70% vs 46%). Any postoperative prostate specific antigen 0.03 ng/ml or greater captured all failures missed by the first postoperative value (100% sensitivity) with accuracy (96% specificity). Defining failure at an ultrasensitive value of 0.03 ng/ml or greater yielded a median lead time advantage of 18 months (mean 24) over the conventional definition of prostate specific antigen 0.2 ng/ml or greater. Ultrasensitive prostate specific antigen 0.03 ng/ml or greater is an independent factor that identifies biochemical relapse more accurately than any traditional risk factors and confers a significant lead time advantage. This factor enables critical decisions on the timing of and indication for postoperative radiotherapy in patients at high risk after radical prostatectomy.

Ultrasensitive Prostate Specific Antigen and its Role after Radical Prostatectomy: A Systematic Review

Prostate specific antigen is an important tool to monitor patients with prostate cancer after radical prostatectomy. Ultrasensitive prostate specific antigen assays are increasingly used with a lower limit of detection as low as 0.001 ng/ml. We systematically reviewed currently available ultrasensitive prostate specific antigen technologies and the role of this method in monitoring patients after radical prostatectomy. We searched the relevant literature using the MEDLINE® database. For various study objectives the series eligible for review provided serial ultrasensitive prostate specific antigen (lower detection limit less than 0.1 ng/ml) data on men after radical prostatectomy as well as comparative data on standard prostate specific antigen (lower detection limit 0.1 ng/ml or greater). Ultrasensitive prostate specific antigen could potentially detect prostate cancer recurrence years earlier than standard prostate specific antigen assays. The specificity of detectable ultrasensitive prostate specific antigen is low. Ultrasensitive prostate specific antigen kinetics may improve the positive predictive value for detecting cancer recurrence. However, the usefulness of prostate specific antigen doubling time at the ultrasensitive level remains controversial. Undetectable nadir ultrasensitive prostate specific antigen after radical prostatectomy confers a low risk of disease recurrence while a detectable nadir above 0.01 ng/ml requires additional measurement and consideration of other risk factors to determine management and avoid overtreatment. This monitoring method may spare patients with high risk disease adjuvant radiation therapy and enable more selective early salvage radiation. Currently no data demonstrate improved survival after early salvage therapy prompted by ultrasensitive prostate specific antigen surveillance. Ultrasensitive prostate specific antigen is useful in the early diagnosis of cancer recurrence after radical prostatectomy but specificity is poor. To date there is a lack of evidence that earlier detection of recurrence translates into prolonged time to metastasis. Integrating ultrasensitive prostate specific antigen with other clinicopathological factors can help determine optimal adjuvant and salvage therapy.

Nucleic Acid Detection Immunoassay for Prostate-Specific Antigen Based on Immuno-PCR Methodology

Serum prostate-specific antigen (PSA) concentrations after radical prostatectomy typically become undetectable with the use of current immunometric assay methods. Despite modern surgical techniques, 15%-30% of prostate cancer patients undergoing radical prostatectomy develop a biochemical recurrence during follow-up. Unfortunately, poor analytical sensitivity of standard PSA assays delays biochemical recurrence detection, and because of day-to-day assay imprecision ultrasensitive PSA assays cannot assess PSA kinetics. We developed an immuno-PCR assay for total PSA that has a limit of quantification >10 times lower than current ultrasensitive assays. The 2-site immunometric assay for total PSA employed 2 monoclonal antibodies, one conjugated to a double-stranded DNA label and the other bound to paramagnetic microparticles. After several washing steps, quantification cycles were determined and values were converted to PSA concentrations. We characterized analytical performance and compared accuracy with a commercially available total PSA assay. The limit of quantification was 0.65 ng/L and the assay was linear in the range of 0.25-152.0 ng/L. Total imprecision estimates at PSA concentrations of 3.8, 24.1, and 69.1 ng/L were <15.2%, <9.4%, and <10.6%, respectively. Recovery of supplemented PSA ranged from 87.5% to 119.2% (mean 100.3%). Dilution recovery ranged from 96.4% to 115.3% (mean 102.3%). There was no high-dose hook effect up to 50 000 ng/L of PSA. Comparison with the commercial PSA assay showed a regression slope of 1.06 and a correlation coefficient of 0.996. The analytical characteristics of the assay support the use of this assay for the accurate and precise measurement of serum PSA, even at sub-nanogram-per-liter concentrations.

Detection of prostate cancer recurrence using an ultrasensitive nanoparticle-based PSA assay

e16146 Approximately 400,000 men are diagnosed each year with prostate cancer worldwide, and many of those patients undergo radical prostatectomy in an attempt to cure the disease. Although prostatectomy is effective for a majority of patients, approximately 15 to 40 % will experience prostate cancer recurrence within 5 years, and a majority of those patients will die from the disease (JAMA. 2008;299:2760-2769). Currently, prostate cancer recurrence is determined by monitoring prostate specific antigen (PSA) levels in patients following treatment, and those patients whose PSA levels rise above the clinical cutoff of 200 pg/mL PSA are defined as having recurrent prostate cancer. For those that do recur and have high PSA doubling times, early salvage radiotherapy confers a significant increase in prostate cancer specific survival (1). We have developed an ultrasensitive assay that measures PSA levels with a limit of detection of 0.5 pg/mL PSA with a CV of less than 20 % at 2 pg/mL. This assay utilizes functionalized gold nanoparticles to label PSA targets captured onto antibody coated glass substrates. The amount of PSA is quantified through silver enhancement of the functionalized gold. In this presentation, we describe the application of this technology in monitoring PSA levels in patients that are approximately 400 fold below the current clinical cutoff as a means of diagnosing prostate cancer recurrence at a much earlier timepoint than current assays. [Table: see text]

Ultrasensitive Prostate Specific Antigen Assay Following Laparoscopic Radical Prostatectomy – An Outcome Measure for Defining the Learning Curve

Radical retropubic prostatectomy (RRP) performed laparoscopically is a popular treatment with curative intent for organ-confined prostate cancer. After surgery, prostate specific antigen (PSA) levels drop to low levels which can be measured with ultrasensitive assays. This has been described in the literature for open RRP but not for laparoscopic RRP. This paper describes PSA changes in the first 300 consecutive patients undergoing non-robotic laparoscopic RRP by a single surgeon. To use ultrasensitive PSA (uPSA) assays to measure a PSA nadir in patients having laparoscopic radical prostatectomy below levels recorded by standard assays. The aim was to use uPSA nadir at 3 months' post-prostatectomy as an early surrogate end-point of oncological outcome. In so doing, laparoscopic oncological outcomes could then be compared with published results from other open radical prostatectomy series with similar end-points. Furthermore, this end-point could be used in the assessment of the surgeon's learning curve. Prospective, comprehensive, demographic, clinical, biochemical and operative data were collected from all patients undergoing non-robotic laparoscopic RRP. We present data from the first 300 consecutive patients undergoing laparoscopic RRP by a single surgeon. uPSA was measured every 3 months post surgery. Median follow-up was 29 months (minimum 3 months). The likelihood of reaching a uPSA of < or = 0.01 ng/ml at 3 months is 73% for the first 100 patients. This is statistically lower when compared with 83% (P < 0.05) for the second 100 patients and 80% for the third 100 patients (P < 0.05). Overall, 84% of patients with pT2 disease and 66% patients with pT3 disease had a uPSA of < or = 0.01 ng/ml at 3 months. Pre-operative PSA, PSA density and Gleason score were not correlated with outcome as determined by a uPSA of < or = 0.01 ng/ml at 3 months. Positive margins correlate with outcome as determined by a uPSA of < or = 0.01 ng/ml at 3 months but operative time and tumour volume do not (P < 0.05). Attempt at nerve sparing had no adverse effect on achieving a uPSA of < or = 0.01 ng/ml at 3 months. uPSA can be used as an early end-point in the analysis of oncological outcomes after radical prostatectomy. It is one of many measures that can be used in calculating a surgeon's learning curve for laparoscopic radical prostatectomy and in bench-marking performance. With experience, a surgeon can achieve in excess of an 80% chance of obtaining a uPSA nadir of < or = 0.01 ng/ml at 3 months after laparoscopic RRP for a British population. This is equivalent to most published open series.

Prostate specific antigen nadir determined using ultra‐sensitive prostate specific antigen as a predictor of biochemical progression after radical prostatectomy in Japanese males

We examined whether the prostate specific antigen (PSA) nadir is a good predictor of biochemical failure after radical prostatectomy. We retrospectively reviewed clinico-pathological data in 257 patients who underwent radical prostatectomy. Twenty-nine patients of whom PSA nadir did not reach 0.1 ng/mL and three patients in whom second line therapy was started before biochemical failure were excluded, and 225 patients were subject to this study. We evaluated the changes in PSA value at very low (from less than 0.01-0.10 ng/mL) levels using an ultra-sensitive PSA assay after radical prostatectomy. Biochemical failure was defined as three consecutive elevations of PSA to above 0.1 ng/mL. Biochemical failure-free survival was attained by 89.9% of patients at 1 year, 83.0% at 2 years, and 81.0% at 5 years. PSA nadir more than 0.01 ng/mL was strongly associated with biochemical failure after radical prostatectomy (P < 0.0001). Mean time to reach PSA nadir was 3.1 months. Preoperative PSA > 20 ng/mL (P = 0.0013), clinical T stage = T2 (P = 0.0462), Gleason score 8-10 (P = 0.0243) were also independent predictors of biochemical progression. Prostate specific antigen nadir determined by ultra-sensitive PSA assay is an important parameter that is objective, reliable, and easily measured, and useful for predicting the subgroups of patients both most likely and unlikely to exhibit biochemical progression.

Efficiency of Ultrasensitive Prostate-specific Antigen Assay in Diagnosing Biochemical Failure After Radical Prostatectomy

Ultrasensitive prostate-specific antigen (PSA) is a significant serum biomarker for identifying the PSA nadir and early biochemical failure after radical prostatectomy (RP). We assessed the efficiency of ultrasensitive PSA assay in the follow-up after RP. We generated longitudinal ultrasensitive PSA data using a computer program assuming that patients experienced biochemical failure after RP. The simulation experiments, based on several different scenarios, were performed to assess the sensitivity and specificity in the diagnosis of biochemical failure using ultrasensitive PSA values and to estimate the lead time, which is the time advantage of detecting positivity for biochemical failure using the ultrasensitive PSA values compared with conventional PSA assay. We validated the sensitivity, specificity and lead time using actual follow-up data of 182 patients receiving RP. It was suggested that the sensitivity obtained from the actual data was more similar to that obtained using ultrasensitive PSA with an exponential increase than with a linear increase in the simulation experiments. Diagnosing biochemical failure based on two consecutive increases in the ultrasensitive PSA values was not recommended. Of non-biochemical failure patients, 9.4% showed four consecutive increases in their ultrasensitive PSA values. Average lead time in the actual data was 11.2 months (SD: 10.1). For an accurate diagnosis of biochemical failure, our findings suggest the importance of a certain duration of follow-up and exclusion of false-positive results afterwards.

Clinicopathological Features of Patients with Biochemical Recurrence after Radical Prostatectomy without Progressive Rise in Serum Prostate-Specific Antigen

Introduction: The objective of this study was to characterize clinicopathological features of patients with biochemical recurrence after radical prostatectomy who did not exhibit a progressive rise in serum prostate-specific antigen (PSA) during the follow-up period. Materials and Methods: We analyzed data from 162 consecutive patients who underwent radical prostatectomy for clinically organ-confined prostate cancer without neoadjuvant hormonal therapy and were followed postoperatively for at least 1 year. The serum PSA value was measured using an ultrasensitive PSA assay system (Roche Diagnostics, Mannheim, Germany), and biochemical recurrence was defined as a serum PSA of ≧0.1 ng/ml. Results: A total of 32 patients (19.8%) were diagnosed as having biochemical recurrence. Among these patients, we identified 10 (31.3%) with a serum PSA >0.1 ng/ml who had not shown PSA or clinical progression during a median follow-up of 34 months after radical prostatectomy. In these 10 patients, the median time to biochemical recurrence was 17 months, the median PSA velocity after biochemical recurrence was 0.034 ng/ml/year, and there was no patient whose serum PSA value became >0.4 ng/ml. There were no clinicopathological parameters except for PSA velocity that were significantly associated with the features of these 10 patients. Conclusion: Because of the presence of a subset of patients with biochemical recurrence after radical prostatectomy who will not show a progressive increase in serum PSA value, the indication for adjuvant therapy for such patients should be cautiously determined considering several factors, such as PSA kinetics.

Usefulness of the Nadir Value of Serum Prostate-Specific Antigen Measured by an Ultrasensitive Assay as a Predictor of Biochemical Recurrence after Radical Prostatectomy for Clinically Localized Prostate Cancer

Introduction: The objective of this study was to determine whether the nadir value of serum prostate-specific antigen (PSA) measured by an ultrasensitive assay could be a useful predictor of biochemical recurrence after radical prostatectomy for clinically localized prostate cancer. Materials and Methods: This study included 127 patients who underwent radical prostatectomy for clinically localized prostate cancer without neoadjuvant hormonal therapy and were pathologically diagnosed as negative for lymph node metastasis. The serum PSA value was measured using an ultrasensitive PSA assay system (Roche Diagnostics, Mannheim, Germany), and the findings were analyzed with respect to several clinicopathological factors. In this series, biochemical recurrence was defined as PSA persistently >0.2 ng/ml. Results: Based on the nadir PSA value, we divided 127 patients into three groups as follows: group A (n = 99): ≤0.01 ng/ml; group B (n = 16): 0.01–0.05 ng/ml, and group C (n = 12): ≧0.05 ng/ml. The nadir PSA value was significantly associated with preoperative PSA value, but not other conventional clinicopathological prognostic parameters. During the observation period (median 31 months, range 6–75 months), biochemical recurrence occurred in 16 patients, that is, 1 in group A (6.3%), 4 in group B (25.0%), and 11 in group C (91.7%). Multivariate analysis using the Cox proportional hazards regression model indicated that the nadir PSA value was an independent predictor for biochemical recurrence after radical prostatectomy. Conclusion: These findings suggest that the nadir serum PSA value measured by an ultrasensitive assay could be a useful predictor of biochemical recurrence after radical prostatectomy for clinically localized prostate cancer, and that careful follow-up should be considered in cases demonstrating a nadir PSA value >0.01 ng/ml because of the significantly higher probability of biochemical recurrence in such cases.

Usefulness of ultrasensitive prostate‐specific antigen assay for early detection of biochemical failure after radical prostatectomy

In order to assess whether the prostate-specific antigen (PSA) nadir obtained with an ultrasensitive PSA assay can be used as a prognostic indicator for patients undergoing radical prostatectomy, we investigated it retrospectively. Between October 1997 and July 2003, 46 patients underwent radical prostatectomy for prostate cancer at our institution. None of them received preoperative treatment. Levels of PSA were measured with an ultrasensitive PSA assay every 1-3 months after prostatectomy. Biochemical recurrence was defined as a PSA level of 0.2 ng/mL or higher. There was a significant difference in PSA nadir between the biochemical recurrence group and the no recurrence group (P < 0.001). The receiver operating characteristics (ROC) curve gave an optimal cut-off value for PSA nadir of 0.01 ng/mL, demonstrating a significant difference in biochemical recurrence after radical prostatectomy. No patient with a PSA nadir level <0.01 ng/mL showed biochemical failure, while 15 out of 22 patients with PSA nadir levels >or=0.01 ng/mL showed biochemical failure. The PSA nadir level obtained using an ultrasensitive PSA assay is an excellent predictor of biochemical recurrence after radical prostatectomy. Early detection of recurrence offers the possibility of early salvage therapy.

Erratum

International Journal of Clinical PracticeVolume 58, Issue 6 p. 648-648 Free Access Erratum First published: 24 June 2004 https://doi.org/10.1111/j.1368-5031.2004.0erratum.xAboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Review article ‘Management of prostate-specific antigen relapse in prostate cancer: A European consensus’. Int J Clin Pract 2004; 58: 382–90. Since publication, it has been brought to our attention that there was a typographical error in the first line of table 1. The corrected table appears as follows: Table 1. Principal conclusions of the European Consensus Group 1. Total prostate specific antigen (PSA) is the most widely used detection tool for prostate cancer; in the PSA range 2-6 ng/ml, free PSA can have a role 2. PSA relapse means treatment failure 3. PSA relapse after radical prostatectomy is defined as a value of 0.2 ng/ml and one subsequent rise. There is a major risk of progression when PSA reaches 0.4 ng/ml 4. The ultrasensitive PSA assay should be used for monitoring patients but not for decision-making 5. Secondary treatment after local failure of surgery should be instigated before PSA levels reach 1.0–1.5 ng/ml 6. The ASTRO definition of PSA failure should be used after radiotherapy. An alternative definition that might be considered is three cumulative rises above nadir 7. Treatment of PSA failure after local therapy depends on whether progression is local or distant. This process is best carried out using a continuous assessment process in the form of a nomogram or artificial neural network 8. Treatment of distant failure involves hormonal manipulation; the type and timing of therapy is based on physician and patient preference 9. For treatment of local failure after radical prostatectomy, salvage radiotherapy can be considered with or without hormonal therapy (Figure 1) 10. Treatment of radiotherapy failure will require prostate biopsy, with imaging conducted on patients with a positive biopsy to confirm absence of distant failure. Local failure should subsequently be treated in well-selected patients with a choice of salvage radical prostatectomy, high-intensity-focused ultrasound, cryotherapy or external beam radiotherapy (Figure 2) 11. A PSA level of <0.4 ng/ml after hormonal therapy can be considered an indicator of a positive response. The use of PSA to monitor second- or third-line interventions is not totally reliable 12. Remember that treating the patient, and not the PSA, remains the physician's primary goal Reference 1 Boccon-Gibod L, Djavan B, Hammerer P et al. Management of prostate-specific antigen relapse in prostate cancer: A European consensus’. Int J Clin Pract 2004; 58: 382– 90. Volume58, Issue6June 2004Pages 648-648 ReferencesRelatedInformation

Relapse and cure rates of prostate cancer patients after radical prostatectomy and 5 years of follow-up

Objectives: We have compared the ability of an ultrasensitive prostate specific antigen assay and a regular PSA assay to identify relapse and cure rates of prostate cancer patients after radical prostatectomy, during a 5-year follow-up period. Design and methods: We measured PSA by an ultrasensitive assay (detection limit 0.001 ng/mL) and a conventional PSA assay (detection limit 0.1 ng/mL) in serial serum samples obtained from 197 patients who have undergone radical prostatectomy. Results: Based on ultrasensitive PSA analysis, we have identified three groups of patients: 62% of patients did not show any significant changes in serum PSA; 15% of patients demonstrated slow PSA increases over time but none of the measurements exceeded 0.1 ng/mL within 4 years; and 23% of the patients had relatively significant increases of serum PSA and were classified as having ‘fast relapse’. The vast majority of these patients were subsequently identified to have relapse by the regular PSA assay. The ultrasensitive PSA assay detected relapse by an average of eighteen months earlier than the conventional PSA method. Fast relapsing patients were associated with other prognostic indicators of the disease including pre-operative PSA, tumor volume, Gleason score, clinical stage, surgical margin positivity, periprostatic tissue involvement, capsular invasion and seminal vesicle invasion. The group with slowly rising PSA had prognosis which was between the patients in remission and fast relapsing patients. Conclusions: The use of ultrasensitive PSA analysis for monitoring patients after radical prostatectomy provides earlier detection of relapse (by 18 months) and identifies three distinct groups of patients. Fast relapsing patients should be good candidates for early therapeutic interventions.

ULTRASENSITIVE DETECTION OF PROSTATE SPECIFIC ANTIGEN IN THE FOLLOWUP OF 422 PATIENTS AFTER RADICAL PROSTATECTOMY

Purpose We validated our ultrasensitive prostate specific antigen (PSA) assay based on lyophilization and 4-fold concentration of patient sera with the clinical long-term followup and according to histopathological characteristics of 422 patients treated with radical retropubic prostatectomy for prostate cancer. Materials and Methods Each serum sample was divided into 2 aliquots for standard and 4-fold concentrated (ultrasensitive) detection. Samples were analyzed by the same unmodified DPC-Immulite 1 PSA assay. Biochemical relapse was defined as an increase of at least 0.10 ng./ml. in native serum (equivalent to 0.025 ng./ml. in concentrated serum). Mean followup was 449 days (range 29 to 2,057). Kaplan-Meier analysis of standard and ultrasensitive detection results was done, and findings were correlated with pathological stage, Gleason grade, total cancer volume, Gleason grade 4 cancer volume and margin status. Significance of earlier detection in ultrasensitive versus standard detection was calculated with the log rank (Mantel-Cox) test with p <0.05 considered significant. Results Of 442 patients 88 (20.8%) experienced biochemical recurrence. Of this cohort 28 (31%) demonstrated early failure on the ultrasensitive assay which was later confirmed on the standard assay, 37 (42%) had failure simultaneously on both assays and 23 (26%) had failure on the ultrasensitive but remained disease-free on the standard assay. Average time for ultrasensitive assay detection of recurrence was 288 days (standard 555). Kaplan-Meier analysis revealed significant advantages in earlier detection of recurrence with the ultrasensitive assay, and close correlation with pathological stage, Gleason grade, margin status and Gleason grade 4 cancer volume. Time advantages of ultrasensitive versus standard detection were greater for advanced cancers (pT3a/b or greater, Gleason 3 + 4 or greater) than for small, low grade tumors. All patients who had positive results on the standard assay had a previous (28) or simultaneous (37) positive ultrasensitive result. With standard detection 25% of all relapse were evident within the first year of surgery and with ultrasensitive detection the percentage increased to 85.7%. On both assays 334 patients remained free of biochemical recurrence. Conclusions Our ultrasensitive PSA assay is useful for early detection of biochemical relapse after radical retropubic prostatectomy. It not only provides the same accuracy as conventional PSA assays but also offers the advantage of detecting recurrence about 300 days earlier. Thus, long-term results of radical retropubic prostatectomy series can be calculated sooner. The clinical impact of this assay will be obvious once curative treatment options are available if applied at the earliest time of evident tumor recurrence.

RADICAL PROSTATECTOMY FOR PROSTATE CANCER: THE PERINEAL APPROACH INCREASES THE RISK OF SURGICALLY INDUCED POSITIVE MARGINS AND CAPSULAR INCISIONS

Purpose We compare the incidence of positive surgical margins in patients who underwent perineal or retropubic radical prostatectomy for clinically localized (stage T1, T2) prostate cancer. Materials and Methods In this retrospective, nonrandomized study we reexamined the specimens of 94 consecutive patients who underwent radical perineal (48) or retropubic (46) prostatectomy for clinically localized prostate cancer (stage T1, T2) and with pathological stage pT2 (intracapsular), pT3A (established extracapsular extension without positive margins) or pT3B (extracapsular extension with positive margins) without lymph node involvement (N0). We assessed the presence or absence of extracapsular cancer with or without positive margins, incisions of the prostatic capsule exposing cancer (surgically induced positive margins) or benign glandular tissue. Patients were followed for 3 to 66 months (mean 25) using an ultrasensitive prostate specific antigen assay with a lower detection limit of less than 0.05 ng./ml. Results The overall incidence of positive margins in cancer tissue was 56% in the perineal and 61% in the retropubic group, and biochemical failure-free survival was 67% each. However, surgically induced positive margins in patients with organ confined disease were more frequent in the perineal than retropubic group (43 versus 29%, p <0.05) and associated with a 37% risk of biochemical failure (prostate specific antigen greater than 0.1 ng./ml.) at mean followup. In addition, capsular incisions exposing benign tissue were more frequent in the perineal than retropubic group (90 versus 37%, p <0.05) irrespective of pathological stage. Conclusions Although overall positive margins and biochemical failure rates are similar or identical for the perineal and retropubic approaches for organ confined prostate cancer, the perineal approach is associated with a significantly higher risk of capsular incisions and surgically induced positive margins and, thus, a higher risk of biochemical failure.

Early detection of recurrent prostate cancer with an ultrasensitive chemiluminescent prostate-specific antigen assay

Objectives Treatment failure after radical prostatectomy is most commonly heralded by an increase in serum prostate-specific antigen (PSA) to detectable levels. We evaluated the clinical utility of an ultrasensitive chemiluminescent PSA assay. Methods We evaluated the assay in banked sera obtained from 170 men after radical prostatectomy. Controls consisted of 142 females, 29 men who had undergone cystoprostatectomy without evidence of prostate cancer and 25 men without evidence of recurrent disease at least 5 years after prostatectomy for organ-confined disease. Lead time to diagnosis of recurrence was based on comparisons with the IMx or Tandem E assays using a cutoff of 0.1 ng/mL (100 pg/mL). Results The biologic level of detection of this assay is 8 pg/mL Serum PSA levels were undetectable in 82.4% of females, 86.2% of the cystoprostatectomy patients, and 96% of the radical prostatectomy controls. After radical prostatectomy, PSA levels were undetectable at last check in 104 of 168 (61.9%) men. In the 24 men with prostate cancer recurrence, the enhanced sensitivity of 8 pg/mL provided a mean lead time based on conservative calculations of 12.7 to 22.5 months over conventional assays. Thirty-four of the 41 men with detectable PSA levels and no evidence of disease recurrence had PSA levels of 30 pg/mL or less. Conclusions PSA levels are undetectable in most men who do not have recurrence of disease after radical prostatectomy. Low but detectable serum PSA levels less than or equal to 30 pg/mL can be produced by nonmalignant sources of PSA. PSA assays with enhanced sensitivity can detect recurrent prostate cancer with significant lead time over conventional assays.