Is screening for prostate cancer with prostate specific antigen an appropriate public health measure?

Screening and treatment for prostate cancer is controversial. In the absence of randomized trials, several prominent medical organizations in the United States and Europe have formulated policies that range from enthusiastic support to significant skepticism concerning the efficacy of screening and subsequent treatment for prostate cancer. Sharp rises in the incidence of prostate cancer have occurred whenever PSA testing has been introduced on a wide scale. Unfortunately, it is unclear whether declines in prostate cancer mortality can be attributed to PSA testing. Other explanations include the early use of anti-androgen therapy or changes in environmental factors such as diet. Repeated testing for serum PSA has produced significant shifts in the types of cases being identified and has raised the possibility of significant over-diagnosis of this disease. The European screening trial and the PLCO trial in the US will hopefully provide some insights into the value of population-based testing.     

Prostate specific antigen as a clinical biomarker for prostate cancer: what's the take home message?

Prostate specific antigen (PSA) continues to be challenged as a legitimate clinical biomarker in early detection of prostate cancer due to lack of specificity for malignant transformation. Skepticism surrounding the utility of serum PSA as a clinical marker is not new and many questioned its initial use in widespread prostate cancer screening due to non-specific expression and low predictive value for cancer detection. Despite these initial concerns, serum PSA measurement along with digital rectal examination (DRE) is currently the accepted practice for prostate cancer screening in the United States with hundreds of thousands of men undergoing serum PSA measurement annually. In contrast to its role for early detection, serum PSA measurement as a surrogate for prostate cancer recurrence (biochemical failure) following curative intent therapy has consummate clinical utility in post-treatment surveillance. As thousands of men each year are aggressively treated for potentially curable prostate cancer, development of simple and effective diagnostic tools for detecting treatment failures should be an important area of biomedical and clinical investigation. We have constructed and tested a home-based prostate cancer surveillance device for use by patients to detect PSA from blood obtained by finger stick. Our initial results suggest that home based PSA testing is feasible and may have clinical utility in management of men treated for prostate cancer.     

Is extended biopsy protocol justified in all patients with PSA ≥ 20 ng/mL？

The aim of this study was to investigate whether it was necessary to increase the number of cores at initial prostate biopsy with patients of prostate-specific antigen （PSA） ≥ 20 ng/mL and to explore an appropriate individualized transrectal ultrasonograhpy （TRUS）-guided prostate biopsy for the detection of prostate cancer in men suspicious of prostate cancer. Methods： A total of 115 patients with PSA ≥ 20 ng/mL and suspicious of prostate cancer were prospectively randomized to perform TRUS-guided biopsy. Patients were randomized to a ＂6 ＋ X＂ cores or a ＂10 ＋ X＂ cores protocol. The primary end point was cancer detection rate. Secondary end points were cancer characteristics, rate of complications and the level of pain experienced by patients during TRUS-guided prostate biopsy. Results： Preoperative variables were similar in both groups. The overall prostate cancer detection rate was 73.9%. The ＂10 ＋ X＂ cores strategy increased cancer detection rate only 9.7% in patients with PSA ≥ 20 ng/mL but 〈 50 ng/mL, while there was no difference between the two strategies for cancer detection in patients with PSA ≥ 50.1 ng/mL. The number of extended biopsy cores and pain score of extended biopsy in prostate cancer patients increased significantly （P 〈 0.001）. Conclusion： Our findings suggest that there is no significant advantage in using extended biopsy protocol in all patients with PSA≥20 ng/mL.     

Is quadrant biopsy sufficient in men likely to have advanced prostate cancer? Comparison with extended biopsy

We hypothesized that quadrant prostate biopsy (QPB) provides sufficient first-line pathological evaluation of patients with presumed advanced prostate cancer (PC). The aim of this study was to investigate whether the reduction of core number in first-line PB from 6-12 to 4 in patients with presumed advanced PC leads to loss of clinically relevant information. We retrospectively studied 113 men that underwent PB, classified in two groups: "H" (high) and "L" (low likelihood of having advanced PC), according to PSA, digital rectal and transrectal ultrasound findings. Pathological results of 6-12-core PB and QPB were retrospectively compared for the presence of malignancy, percentage of positive cores, Gleason score (GS), and the presence of high-grade prostatic intraepithelial neoplasia (HGPIN). PC detection rate was not impaired in group H but dropped significantly in group L, and the percentage of positive cores was not significantly changed in group H (p=0.39), but decreased in group L (p=0.04), due to sampling scheme reduction. No HGPIN was missed with QPB in group H, while 2 HGPINs were missed in group L. No significant change in GS in either group was observed (p=0.12, p=0.13) due to reduction to QPB. We conclude that in patients with presumed advanced PC, reduction of the number of cores in PB may be an acceptable diagnostic strategy, but further studies are needed to analyze the impact of PB scheme reduction on other relevant pathological information obtained from PB.     

The lady with raised prostate specific antigen: do we need to worry?

Background: Prostate specific antigen (PSA) is generally considered a biological marker of prostate cancer although raised values may also be observed in benign prostatic diseases. PSA can be secreted in females from skeine’s periurethral gland but at low levels. This case - control study aimed at the evaluation of relation of PSA with different diseases in women. Method: A total of 297 patients were included, 107 with breast cancer, 90 with benign breast disease (BBD) and 100 controls (patients attending our surgery department for non-breast diseases). PSA was measured in the serum of all and a statistical analysis was conducted. Result: An association of raised PSA with breast diseases was observed. Total PSA was more sensitive for benign breast diseases, whereas breast cancer showed a predilection towards increase in free PSA. PSA decreased after surgery. Conclusion: PSA can be used as a diagnostic and prognostic marker of breast cancer in women, therefore helping secondary prevention of breast cancer.     

Prostate-specific antigen and detection of prostate cancer: What have we learned and what should we recommend for screening?

Opinion statement Prostate-specific antigen (PSA) has become one of the most commonly used cancer clinical tests, and routine PSA-based screening has led to a dramatic increase in prostate cancer detection. A significant downward stage migration has resulted, and a decrease in prostate cancer mortality has also been observed. However, PSA screening remains controversial because there is no definitive proof that it decreases prostate cancer death rates, and there is concern that it may detect a significant number of clinically insignificant cancers. Screening age and interval have been recently questioned, and the best threshold to recommend biopsy has been complicated by new data showing that prostate cancer exists at all PSA levels, even those thought to be “normal” in the past. It is hoped that ongoing prospective screening trials will determine the value of PSA screening. However, until these results are available the controversy will continue, and men will continue to be screened.     

Do the risk factors of age,family history of prostate cancer or a higher prostate specific antigen level raise anxiety at prostate biopsy?

To date, little is known of the impact knowledge of personal risk factors has on anxiety in men undergoing biopsy tests for prostate cancer. This analysis explores anxiety scores of men at higher risk due to age, family history of prostate cancer and a higher prostate specific antigen (PSA) level when proceeding from PSA test to prostate biopsy. A prospective cohort of 4198 men aged 50–69 years with a PSA result of >3 ng/ml was studied, recruited for the Prostate testing for cancer and Treatment study (ProtecT). Anxiety scores at the time of biopsy were lower in older men (p < 0.001). No age group showed an increase in anxiety as the men proceeded from PSA testing to biopsy, although older men did not show the same level of decrease in anxiety as younger men (p = 0.035). There was no difference in anxiety scores at biopsy between men with or without a family history of prostate cancer (p = 0.68), or between those with a raised PSA of 10–<20 ng/ml compared to a PSA result of 3–<10 ng/ml (p = 0.46). Change in scores since the initial PSA test appeared unaffected by family history (p = 0.995) or by PSA result (p = 0.76). Within the context of a research study, the increased risk of prostate cancer through older age, having a family history of prostate cancer, or having a significantly elevated PSA level appears to have no detrimental effect on men’s anxiety level when proceeding to biopsy.     

Should men with serum prostate-specific antigen < or =4 ng/ml and normal digital rectal examination undergo a prostate biopsy? A literature review

The clinical significance of a prostate cancer (PCa) cannot be determined solely by tumor volume (< or =0.5 cm(3)), as small tumors of higher Gleason grade and tumors occurring in younger men may become clinically significant even though the initial volume at diagnosis is small. A certain number of these minimal cancers are likely to remain clinically insignificant; however, it is unpredictable how many can progress beyond the curable stage by the time there is a rise in serum prostate-specific antigen (PSA) values. Compared to clinically detected PCa, PCa detected exclusively by PSA screening (clinical stage T1c) are less likely to be advanced but no more likely to be insignificant in terms of volume, pathologic stage, and Gleason pattern. Only 10-15% of PSA-detected cancers have the features of PCa found at autopsy or in cystoprostatectomy specimens. Actually, 25-30% of PCa are detected with PSA values between 2.5 and 4 ng/ml, and most of these cancers are clinically significant. Evidence from both retrospective and longitudinal studies has shown that the risk of a PCa is dependent on the patient's age and the initial serum PSA. This allows an individualized approach to PCa screening programs, and PSA cutoff values for biopsy indication may be lowered in selected patients.     

Transperineal ultrasound-guided 12-core systematic biopsy of the prostate for patients with a prostate-specific antigen level of 2.5–20 ng/ml in Japan

Background The aim of this study was to investigate the cancer detection rate in patients with a prostate-specific antigen (PSA) level of 2.5 to 20ng/ml, using transperineal ultrasound-guided systematic biopsy of the prostate.Methods Three hundred consecutive patients with PSA levels of 2.5 to 20ng/ml underwent transperineal ultrasound-guided 12-core systematic biopsy of the prostate.Results Prostate cancer was detected in 108 of the 300 patients (36.0%). The cancer detection rates in patients with total PSA levels of 2.5–4.0, 4.01–10.0 and 10.01–20.0ng/ml were 18.2%, 31.0%, and 50.0%, respectively. The cancer detection rates in patients with prostate volumes of less than 30cc and over 50cc were almost 50%, and 13.3%, respectively. The cancer detection rate in patients with a PSA density (PSAD) of less than 0.10ng/ml per cc was only 5.6%, and no prostate cancer was detected in patients with a free-to-total PSA ratio (% f PSA) over 40%.Conclusion We demonstrated a high prostate cancer detection rate by the transperineal ultrasound-guided 12-core systematic biopsy method in patients with PSA levels of 2.5 to 20ng/ml. Accordingly, if the number of core biopsies is further increased overall, except in patients with a large prostate volume, and if the indication for biopsy is decided based on the PSAD and %f PSA, then the cancer detection rate by the present method may be further improved, with fewer unnecessary biopsies.     

Molecular forms of prostate‐specific antigen in serum with concentrations of total prostate‐specific antigen <4 μg/L: Are they useful tools for early detection and screening of prostate cancer?

Molecular forms of prostate-specific antigen (PSA) improve the differentiation between benign prostatic hyperplasia (BPH) and prostate cancer (PCa) in men with total PSA concentrations between 4 and 10 microg/l. To evaluate the diagnostic utility of free PSA (fPSA) and complexed PSA forms for identification of men with PCa in the low PSA range of <4 microg/l, total PSA (tPSA), alpha(1)-antichymotrypsin complexed PSA (PSA-ACT) and fPSA (Roche Elecsys [ES] system) as well as tPSA and complexed PSA (cPSA) (Bayer Immuno 1 system) were measured in archival serum samples from 31 untreated patients with PCa, 66 patients with BPH, and 90 men without prostatic disease. The median ratios of fPSA/tPSA, PSA-ACT/tPSA and cPSA/tPSA were significantly different between patients with BPH and PCa (27.2 vs. 19.4%, 64 vs. 88%, 77.2 vs. 88.2%, p < 0.05). No associations between PSA forms and tumor stage and grade were found. Analysis of the receiver operating characteristic curves showed that these ratios could discriminate better between BPH and PCa patients than determination of the analytes tPSA, fPSA, cPSA and PSA-ACT alone. The use of one of the ratios would have eliminated roughly half of the unnecessary biopsies in this study. The ratios should be considered as potential tools to increase the selectivity of PCa detection at low PSA concentration. The ratios fPSA/tPSA and cPSA/tPSA can be determined using commercially available assays so that one of these ratios could be preferred instead of PSA-ACT determination. The ratios could be useful in assessing the risk of PCa in the individual and therefore in deciding on prostate biopsy for final diagnosis.     

Why are pretreatment prostate‐specific antigen levels and biochemical recurrence poor predictors of prostate cancer survival?

BACKGROUND:

The value of pretreatment (initial) prostate‐specific antigen (iPSA) and biochemical recurrence (BR) as prognostic factors for survival remains unclear. The authors sought to determine why using randomized trial data with 7‐year minimum follow‐up.

METHODS:

In the Trans‐Tasman Radiation Oncology Group 96.01 trial, 802 men with T2b, T2c, T3, or T4 N0 prostate cancer (PC) were randomized to radiotherapy alone or with 3 or 6 months neoadjuvant androgen deprivation between 1996 and 2000. Cox modeling was used to identify outcome predictors at follow‐up landmark points.

RESULTS:

Higher iPSA was found to be a potent predictor of BR–free survival (P < .01) but was not prognostic for prostate cancer–specific survival (PCSS) from randomization. Patients experiencing BR had unfavorable initial prognostic factors compared with patients who did not. After BR, these factors were not prognostic for PC death in models adjusted for time to BR (TTBR). In these models, TTBR predicted PCSS more satisfactorily than the occurrence of BR itself. Survival probability 5 years after BR exceeded 90% for men with TTBR ≥4 years; however, it dropped to 44% ± 6% for men with TTBR <1 year. After BR, rapid PSA doubling time (DT), low iPSA, and short TTBR were identified as the most important predictors of inferior PCSS.

CONCLUSIONS:

When BR occurs, prognostic factors for survival change. Low iPSA, short TTBR, and rapid PSA DT take over at this point, providing reasons why iPSA and occurrence of BR alone predict PCSS unsatisfactorily. Cancer 2009. © 2009 American Cancer Society.     

Strontium‐89 treatment for prostate cancer bone metastases: Does a prostate‐specific antigen response predict for improved survival?

A review of 50 patients treated with strontium‐89 for prostate cancer bone metastases from January 1993–1997 at the Wellington Cancer Centre was undertaken to determine if there was any correlation between changes in prostate‐specific antigen (PSA) following treatment and subsequent survival. Thirty cases were evaluable for PSA response. Of these, 14 had a fall in PSA following strontium‐89 treatment, and their mean survival was 641 days. The remaining 16 patients did not demonstrate a post‐treatment fall in PSA and their mean survival was 275 days. A difference between these two groups in the time to development of new bone symptoms following treatment was also observed. No significant correlation between pretreatment PSA and PSA response was observed. In conclusion, a PSA response following strontium‐89 treatment appears to predict for improved survival in patients with bone metastases from carcinoma of the prostate. Further prospective studies are indicated.     

Aged patients with metastatic castration resistant prostate cancer: Should we treat with chemotherapy?

Prostate cancer largely affects aged men and as life expectancy continues to increase, it is likely to be a growing burden requiring an adequate management. Aging is a heterogeneous process, thus, to assess the individual state of health when making decisions is essential. Comprehensive geriatric assessment allows a detailed evaluation of the state of health of a specific subject and can modify the therapeutic decision. It is still not commonly used because it is time consuming. Chemotherapy should be administered equally in aged well-fit patients as in the general population as per the SIOG (International society of geriatric oncology) recommendations for geriatric evaluation and treatment in prostate cancer patients. Chemotherapy with docetaxel or cabazitaxel is expected to have an efficacy and toxicity similar to younger patients and they might be considered treatment options for these patients among others. In vulnerable or frail patients, weekly or biweekly docetaxel regimens are acceptable treatment options.     

Diagnostic value of urine prostate cancer antigen 3 test using a cutoff value of 35 μg/L in patients with prostate cancer

The aim of this study is to explore the diagnostic role of urine prostate cancer antigen 3 (PCA3) in detecting prostate cancer (PCa) through a systematic review and meta-analysis. Relevant research studies aiming at the application of urine PCA3 level in PCa diagnosis were searched in PubMed, Embase, Chinese Biomedical Database (CBM), Chinese National Knowledge Infrastructure (CNKI), VIP, and Wan Fang databases independently, which were published up to May 8, 2014. The pooled sensitivity, specificity, positive diagnostic likelihood ratio (DLR+), negative diagnostic likelihood ratio (DLR?), diagnostic odds ratio, and the area under the summary receiver operating characteristic were used to evaluate the value of urine PCA3 in diagnosis of PCa by using the Meta-DiSc and STATA 12.0 statistical software. Sixteen research studies with a total 2,457 PCa patients and 4,236 control individuals were included in this meta-analysis. Overall, the results showed sensitivity and specificity of urine PCA3 in the diagnosis of PCa was 0.57 (95 % CI?=?0.55–0.59), and 0.71 (95 % CI?=?0.70–0.73), respectively. The DLR + and PLR ? in the diagnosis of PCa were 2.12 (95 % CI?=?1.89–2.38), and 0.55 (95 % CI?=?0. 50–0.61), respectively. The pooled diagnostic odds ratio was 3.93 (95 % CI?=?3.28–4.72). The area under the curve (AUCs) and *Q index estimate were 0.7118 and 0.6623, respectively. Urine PCA3 is a potential biomarker for the diagnosis of PCa. However, further well-designed studies with large samples will be needed to confirm the results got from present meta-analysis.     

Intra-operative pubic arch interference during prostate seed brachytherapy in patients with CT-based pubic arch interference of ?1 cm

Purpose

There are only a few reports on the frequency of intra-operative pubic arch interference (I-PAI) during prostate seed brachytherapy (PB).

Materials and methods

Two hundred and forty-three patients with a CT-based pubic arch interference (PAI) of ?1 cm and a prostate volume of ?50-60 cc underwent PB. Those patients requiring needle repositioning by ?0.5 cm on the template were scored as having I-PAI. The incidence of I-PAI and its impact on biochemical control were analyzed.

Results

Intra-operative PAI was encountered in 47 (19.3%) patients. Forty two patients (17.3%) had I-PAI in 1-2 needles, two (0.8%) had I-PAI in four needles and three patients (1.2%) had I-PAI in six needles. Overall, 1.4% of needles required repositioning due to I-PAI. BMI > 27 kg/m² and wider (>75 mm) pubic bone separation at mid ramus (PS-ML) were associated with a lower incidence of I-PAI. At a median follow-up of 50.1 months, the 3- and 5-year bPFS was 97.3% and 95.2%, respectively. The 5-year bPFS rates for patients with and without I-PAI were 95.6% and 95%, respectively (p = 0.28).

Conclusions

The use of CT-based PAI of ?1 cm as a selection criterion for PB is a simple and reliable method for minimizing the incidence of I-PAI and maintaining excellent biochemical control rates.