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.     

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.     

The clinical management of patients with a small volume of prostatic cancer on biopsy: What are the risks of progression?

Clinically localized prostate cancer is associated with a wide variation in biologic behavior, and men with the less aggressive form of the disease may never develop symptoms. There has been a rise in prostate cancer incidence in countries in which the blood test for prostatic-specific antigen (PSA) is common, and concerns have been expressed that this may be because of the increased detection of indolent disease, subjecting these men to unnecessary treatment and associated side effects. For the current review, the authors conducted a systematic evaluation of the literature regarding the outcomes of men who were diagnosed on the basis of a small volume of cancer in prostatic biopsies. The results indicated that, despite differences in study design and reporting, a significant proportion of patients with microfocal cancer, regardless of how it was defined, had adverse pathologic findings and a significant risk of PSA recurrence after undergoing radical prostatectomy. Biochemical and clinical recurrences also were observed after radiotherapy or watchful waiting. The authors concluded that patients with microfocal carcinoma on biopsy should be advised that their disease is not necessarily "insignificant" and should be counseled accordingly.     

Liquid biopsy and non-small cell lung cancer: are we looking at the tip of the iceberg?

The possibility to analyse the tumour genetic material shed in the blood is undoubtedly one of the main achievements of translational research in the latest years. In the modern clinical management of advanced non-small cell lung cancer, molecular characterisation plays an essential role. In parallel, immunotherapy is widely employed, but reliable predictive markers are not available yet. Liquid biopsy has the potential to face the two issues and to increase its role in advanced NSCLC in the next future. The aim of this review is to summarise the main clinical applications of liquid biopsy in advanced non-small cell lung cancer, underlining both its potential and limitations from a clinically driven perspective.Subject terms: Non-small-cell lung cancer, Tumour biomarkers     

Can core biopsy be used instead of surgical biopsy in the diagnosis and prognostic factor analysis of breast carcinoma?

PURPOSE: The aim of this article was to investigate the efficacy of ultrasonography-guided core needle biopsy and prognostic factor analysis of breast cancer to plan overall treatment strategy. PATIENTS AND METHODS: A consecutive series of nonpalpable and palpable breast cancers constituted our study group (n= 201 lesions; mean size, 20.4 mm) Mean number of core samples was 3.4. Malignant lesions diagnosed with core biopsy underwent therapeutic surgical excision. Core biopsy and surgical excisions were compared for histologic type, grade, estrogen receptors (ERs), progesterone receptors (PgRs), and c-erbB2 levels. Cutoff values for ER, PgR, and c-erbB2 affecting the management strategy were selected as 10%, 10%, and 50%, respectively. RESULTS: Eighty-five lesions (42.3%) were malignant in core biopsy (mean size, 18.4 mm). Among these, 11 were inoperable and 13 were surgically excised at other institutions. In 61 lesions, core and surgical excision specimens were evaluated in the same institution (mean tumor size, 18.6 mm; range 6-60 mm). Concordance between the 2 biopsy methods was 85.2% (52 of 61) for histologic type of tumor, 68.8% (33 of 48) for tumor grade, 90% (27 of 30) for ER, 86.7% (26 of 30) for PgR, and 79.3% (23 of 29) for c-erbB2 levels. Appropriate site selection for sampling was indicated to be of paramount importance, especially in determining reliable ER, PgR, and c-erbB2 levels. CONCLUSION: Core needle biopsy of breast cancer is equally effective compared with surgical biopsy and can be used in overall treatment planning. However, appropriate site selection for sampling should be guaranteed using ultrasonographic guidance.     

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.     

Staging of head and neck cancers: is it time to change the balance between the ideal and the practical?

The TNM system is a widely accepted prognostic system worldwide. Limitations in prognostic accuracy are recognized but have remained for fear the remedy would unnecessarily complicate the system. Understanding of the genetic and molecular mechanisms of cancer will allow the gap between the ideal and the practical prognostic system to be closed and the staging system drastically revised to a modular structure. Novel computational technology, which is reliable and reproducible, is likely to provide the basis for such a modular prognostic system.     

A plea for the biopsy marker: how,why and why not clipping after breast biopsy?

In the last decade, percutaneous breast biopsies have become a standard for the management of breast diseases. Biopsy clips allow for precise lesion localization, thus minimizing the volume of breast to be resected at the time of surgery. With the development of many imaging techniques (including mammography, sonography, and breast magnetic resonance imaging), one of the challenges of the multidisciplinary became to synthesize all informations obtained from the various imaging procedures. The use of biopsy markers after percutaneous biopsy is one of the keys for optimal patient management, helping the radiologist to deal with multiple lesions, to insure correlation across different imaging modalities and to follow-up benign lesions, helping the oncologist by marking a tumor prior to neoadjuvant chemotherapy, helping the surgeon by facilitating preoperative needle localization, to precisely mark the margins of extensive disease and to guide intraoperative tumor resection, and helping the pathologist to insure the lesion of interest has been removed and to identify the region of interest in a mastectomy specimen. We believe biopsy clip markers should be deployed after all percutaneous interventions and present in this review the arguments to support this statement. Minimal indications for clip deployment will also be detailed.     

PSA use and incidence of prostate biopsy in the Tuscany region: is opportunistic screening discounting biopsy in subjects with PSA elevation?

AIMS AND BACKGROUND: To assess PSA use in the general population and estimate biopsy rate subsequent to opportunistic screening. METHODS AND STUDY DESIGN: We report on PSA testing and related prostate biopsy frequency in the Tuscany Region during 2004-2005 to establish current patterns of care. We used population data sources to survey PSA testing and biopsy and estimated expected PSA values and expected recommended biopsies (> or = PSA 4 ng/ml) from the ongoing Florence arm of the European Study of Screening for Prostate Cancer (ERSPC). RESULTS: PSA testing was common for both years and across age groups, increasing with age and peaking at 70-74 years (37.6% in 2004, 41.9% in 2005) and increasing over the 2 years. PSA use in the 55-69 years cohort (screening age in ERSPC) was 28.3% in 2004 and 30.4% in 2005. Repeat PSA testing was also common and repeat PSA probability increased with age, peaking at age 70-74 (60.9%); repeat PSA testing at age 55-69 was 53.7%. Overall, 1.3% and 1.2% of men had a biopsy following PSA testing in 2004 and 2005. Observed/expected biopsy incidence was 14.3% in 2004 and 13.2% in 2005. ERSPC compliance to recommended biopsy was 77% or 60% at first or repeat screening. CONCLUSIONS: A discordance was identified between high PSA testing prevalence and low prostate biopsy rate. Based on projections from the ERSPC, this indicates a much lower observed biopsy rate than expected in organized screening. Although the implications of this are difficult to quantify in the absence of evidence on screening efficacy, it suggests inefficient practice.     

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.     

Investigating the prostate specific antigen,body mass index and age relationship: is an age–BMI-adjusted PSA model clinically useful?

Purpose

Previous studies indicate a possible inverse relationship between prostate-specific antigen (PSA) and body mass index (BMI), and a positive relationship between PSA and age. We investigated the associations between age, BMI, PSA, and screen-detected prostate cancer to determine whether an age–BMI-adjusted PSA model would be clinically useful for detecting prostate cancer.

Methods

Cross-sectional analysis nested within the UK ProtecT trial of treatments for localized cancer. Of 18,238 men aged 50–69 years, 9,457 men without screen-detected prostate cancer (controls) and 1,836 men with prostate cancer (cases) met inclusion criteria: no history of prostate cancer or diabetes; PSA < 10 ng/ml; BMI between 15 and 50 kg/m². Multivariable linear regression models were used to investigate the relationship between log-PSA, age, and BMI in all men, controlling for prostate cancer status.

Results

In the 11,293 included men, the median PSA was 1.2 ng/ml (IQR: 0.7–2.6); mean age 61.7 years (SD 4.9); and mean BMI 26.8 kg/m² (SD 3.7). There were a 5.1% decrease in PSA per 5 kg/m² increase in BMI (95% CI 3.4–6.8) and a 13.6% increase in PSA per 5-year increase in age (95% CI 12.0–15.1). Interaction tests showed no evidence for different associations between age, BMI, and PSA in men above and below 3.0 ng/ml (all p for interaction >0.2). The age–BMI-adjusted PSA model performed as well as an age-adjusted model based on National Institute for Health and Care Excellence (NICE) guidelines at detecting prostate cancer.

Conclusions

Age and BMI were associated with small changes in PSA. An age–BMI-adjusted PSA model is no more clinically useful for detecting prostate cancer than current NICE guidelines. Future studies looking at the effect of different variables on PSA, independent of their effect on prostate cancer, may improve the discrimination of PSA for prostate cancer.

     

Is there an indication for sentinel node biopsy in patients with ductal carcinoma in situ of the breast? A review

Ductal carcinoma in situ (DCIS) of the breast is defined as a proliferation of malignant epithelial cells within breast ducts without evidence of invasion through the basement membrane. The detection rate of DCIS of the breast has dramatically increased since the mid-1980s as the result of the widespread use of screening mammography. DCIS currently represents about 15-25% of all breast cancers detected in population screening programmes. Although inherently a non-invasive disease, occult invasion with the potential of lymph node metastases may occur. Where performing an axillary lymph node dissection-or-not for DCIS used to be an important dilemma, the same now holds for the sentinel node biopsy. This article reviews the potential role of the sentinel node biopsy (SNB) in patients with DCIS. We conclude that based on the current literature, there is in general no role for a SNB in DCIS. A SNB should only be considered in patients with an excisional biopsy diagnosis of high risk DCIS (grade III with palpable mass or large tumour area by imaging) as well as in patients undergoing mastectomy after a core or excisional biopsy diagnosis of DCIS, although SNB may be contraindicated in many of the latter patients because of lesion size and/or multifocality. Even in these patients the value of a positive SN, containing mostly isolated tumour cells, is questionable.