The accuracy of multiparametric MRI in men with negative biopsy and elevated PSA level—Can it rule out clinically significant prostate cancer?

PurposeTo assess the performance of multiparametric magnetic resonance imaging (mp-MRI) in patients with previous negative transrectal ultrasound (TRUS) guided prostate biopsy.Materials and methodsFifty-four patients with at least 1 previous negative TRUS prostate biopsy underwent mp-MRI in the form of T2-weighted, diffusion-weighted, and dynamic contrast-enhanced imaging. This was followed by transperineal template systematic prostate biopsies. Analysis was done based on 2 sectors per prostate, right and left (108 sectors out of 54 prostates). mp-MRI was scored using an ordinal scale 1 to 5 based on the suspicion of the presence of clinically significant disease. We used 6 different definitions for clinically significant disease and tested the performance of mp-MRI at each single definition.ResultsMedian age was 64 (range, 39–75), median PSA level was 10 (range, 2–23), and median number of biopsies was 45 (range, 21–137). Cancer of any volume and any grade was detected in 34 of 54 (63%) patients. mp-MRI accuracy at detection of clinically significant cancer using University College London (UCL) definition 2 (any Gleason score of 4 or maximum cancer core length of ≥4 mm or both) showed sensitivity of 76%, specificity of 42%, positive predictive value of 38%, and negative predictive value of 79%. For a different definition of significant tumor (UCL definition 1; dominant Gleason score 4 or maximum cancer core length ≥6 mm or both), the sensitivity was 90%, specificity 42%, positive predictive value 26%, and negative predictive value 95%.Conclusionsmp-MRI showed good performance at both detection and ruling out clinically significant disease, according to the definition used. mp-MRI can then be used as a triage test in the population with persistently elevated or rising PSA levels to select patients that can avoid unnecessary prostate biopsy.     

Formalized prediction of clinically significant prostate cancer: is it possible?

Greater understanding of the biology and epidemiology of prostate cancer in the last several decades have led to significant advances in its management. Prostate cancer is now detected in greater numbers at lower stages of disease and is amenable to multiple forms of efficacious treatment. However, there is a lack of conclusive data demonstrating a definitive mortality benefit from this earlier diagnosis and treatment of prostate cancer. It is likely due to the treatment of a large proportion of indolent cancers that would have had little adverse impact on health or lifespan if left alone. Due to this overtreatment phenomenon, active surveillance with delayed intervention is gaining traction as a viable management approach in contemporary practice. The ability to distinguish clinically insignificant cancers from those with a high risk of progression and/or lethality is critical to the appropriate selection of patients for surveillance protocols versus immediate intervention. This chapter will review the ability of various prediction models, including risk groupings and nomograms, to predict indolent disease and determine their role in the contemporary management of clinically localized prostate cancer.     

Is endorectal coil necessary for the staging of clinically localized prostate cancer? Comparison of non-endorectal versus endorectal MR imaging

Purpose

The goal of this study was to compare the diagnostic use and safety of endorectal coil (ERC) MRI with those of phased-array coil MRI.

Methods

We retrospectively included 91 consecutive patients who had undergone 1.5-T MRI with ERC or with phased-array coil MRI before radical prostatectomy at our institution. We compared 47 patients’ phased-array coil MRI and 44 patients’ ERC-MRI with histologic findings. We also evaluated adverse events following the MRI procedure.

Results

The serum PSA levels ranged from 2.85 to 33.51 ng/mL (10.72 ± 1.9), and the median Gleason score was 7 (range 4–9). The mean interval between diagnostic prostate biopsy and staging MRI was 18.4 days (range 2–37). In assessing organ-confined disease, extracapsular extension and seminal vesicle invasion by MRI, there were no significant differences between ERC-MR group and phased-array coil MR group. The AUC values were 0.671 (95% CI 0.530–0.813) for ERC-MR and 0.657 (95% CI 0.503–0.811) for phased-array coil MR. No significant differences were found between the two groups (p = 0.24). Five patients (11.4%) developed rectal complications after ERC-MRI. However, no complications were found in phased-array coil MRI group.

Conclusions

In terms of diagnostic accuracy and comfort of patients, the use of ERC-MRI did not significantly improve the staging of prostate cancer and presented several complications. Therefore, phased-array coil MRI is a better alternative considering comorbidity.     

Is systematic sextant biopsy suitable for the detection of clinically significant prostate cancer?

BACKGROUND: The optimal extent of the prostate biopsy remains controversial. There is a need to avoid detection of insignificant cancer but not to miss significant and curable tumors. In alternative treatments of prostate cancer, repeated sextant biopsies are used to estimate the response. The aim of this study was to investigate the reliability of a repeated systematic sextant biopsy as the standard biopsy technique in patients with significant tumors which are being considered for curative treatment. METHODS: Systematic sextant biopsy was performed in vitro in 92 radical prostatectomy specimens. Of these patients, 81 (88.0%) had palpable lesions. RESULTS: Of the 92 investigated patients, 70 (76.1%) had potentially curable pT2-3pN0 prostate cancers. In these patients, the cancer was detected only in 72.9% of cases by a repeated in vitro biopsy. In the pT2 tumors, there was a detection rate of only 66.7%. CONCLUSIONS: This study underlines the fact that a considerable number of significant and potentially curable tumors remain undetected by the conventional sextant biopsy. A negative sextant biopsy does not rule out significant prostate cancer.     

Can prostate cancer be prevented?

The goal of primary chemoprevention is to decrease the incidence of a given cancer, simultaneously reducing both treatment-related adverse events and mortality. Prostate cancer is an attractive and appropriate target for primary prevention because of its incidence, prevalence, and disease-related mortality; its long latency and molecular pathogenesis; and epidemiologic data indicating that modifiable environmental factors may decrease risk. The Prostate Cancer Prevention Trial (PCPT) demonstrated that finasteride can prevent prostate cancer, albeit with an apparently increased risk of high-grade disease. A substantial amount of epidemiologic, molecular, and clinical evidence suggests that both selenium and vitamin E might also prevent prostate cancer, and this combination is being tested in the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Ultimately, the adoption of a preventive strategy hinges on its potential benefits weighed against the potential risks of the specific agents used.     

Does presence of prostate cancer affect serum testosterone levels in clinically localized prostate cancer patients?

The relationships between serum level of testosterone (T) and prostate cancer (PCa) are complex. The present study evaluated whether presence of PCa alters serum T levels. Subjects were 125 patients with clinically localized PCa treated using radical prostatectomy (RP), for whom pretreatment T levels were recorded. We investigated clinical and pathological factors such as pretreatment serum T level, age, pretreatment prostate-specific antigen, Gleason score and pathological stage. Serum T and human luteinizing hormone (LH) levels before and after RP were then compared in 118 of the 125 patients. Mean pretreatment T level was significantly higher in patients with organ-confined PCa (pT2; 4.03+/-1.50 ng ml(-1)) than in patients with nonorgan-confined cancer (pT3; 3.42+/-1.06 ng ml(-1); P=0.0438). No association existed between pretreatment serum T level and pathological Gleason score. After RP, serum T level (5.60+/-1.90 ng ml(-1)) was significantly elevated compared to preoperative level (3.89+/-1.43 ng ml(-1); P<0.0001). In parallel, significant increases were seen in postoperative serum LH level (6.86+/-3.64 ng ml(-1)) compared to preoperative level (5.11+/-2.47 ng ml(-1); P=0.0001). In contrast, differences in serum T levels according to pathological stage disappeared postoperatively (P=0.5513). Significant increases in serum T and LH levels were seen after RP, compared to preoperative levels in parallel. This study suggests that serum T levels are altered by the presence of PCa, supporting the possibility that PCa may inhibit serum T levels with negative feedback in the hypothalamic-pituitary axis.     

Can we prevent prostate cancer? Rationale and current status of prostate cancer chemoprevention

Prostate cancer has been one of the most frequent cancers among men in Western countries for the past decade. Investigation of prostate cancer prevention is very attractive, because prostate cancer has a high incidence, long-term natural history, regional difference in incidence, and is effected by sex steroids. Chemoprevention is defined as the use of specific agents to suppress or reverse carcinogenesis and to prevent the development of cancer. The development of chemoprevention strategies against prostate cancer would be of medical and economic importance. Basic and clinical research of chemoprevention of prostate cancer are under active investigation. This article aims to summarize and review the basic evidence and clinical trials on prostate cancer chemoprevention. Recent research has demonstrated that many agents, such as agents altering sex steroid signaling, drugs inducing antiproliferation/differentiation, retinoids, anti-inflammatory drugs, and antioxidants, could be potential preventatives for prostate cancer. Large-scale clinical trials have suggested that 5alpha-reductase inhibitor finasteride, selenium, and vitamin E can function as a chemopreventive agent. Although no definitely effective strategies of prostate cancer prevention have been identified yet, increasing evidence will provide effective and safe strategies that bring clinical benefits.     

Are predictive models for cancer volume clinically useful in localized prostate cancer?

Objectives: To evaluate the correlation between preoperatively predicted and pathologically measured prostate cancer volumes and to investigate the clinical use of preoperatively predicted cancer volume in predicting pathological stage. Methods: Correlations between pathological findings and various preoperative parameters, including the cancer volumes as predicted by using two methods (Vca and estimated PCvol), were analyzed in 196 patients who underwent radical prostatectomy for clinically localized prostate cancer. Results: Pathologically measured prostate cancer volume was significantly correlated with the Vca and estimated PCvol, but the correlation coefficients were respectively only 0.46 and 0.35. Prostate‐specific antigen (PSA), PSA density (PSAD), primary Gleason score, Vca, Vca fraction (Vcafx), and estimated PCvol were significantly higher in 82 patients with extraprostatic cancer than in 114 patients with organ‐confined cancer. Magnetic resonance imaging (MRI) findings were significantly correlated with pathological stage. Multivariate logistic regression analysis indicated that the Vcafx and MRI findings were significant predictors of extraprostatic cancer, but receiver operating characteristic analysis revealed that the combination of Vcafx and MRI findings had no advantage over the combination of Gleason score, PSAD, and MRI findings. Conclusions: Vca and estimated PCvol are significantly correlated with the pathologically measured cancer volume but their ability to accurately predict cancer volume is limited. Vcafx and MRI findings were statistically significant predictors of extraprostatic cancer but their combination was not superior to the combination of Gleason score, PSAD, and MRI findings.     

Can mycoplasma contribute to formation of prostate cancer?

Purpose

To reveal the possible role of mycoplasmas in the etiopathogenesis of prostate cancer.

Methods

In the study, prostate biopsy was performed on 62 patients with an abnormal digital rectal examination and/or elevated PSA. The patients’ age was between 62 and 77 (mean 65.4 years) years. Thirty-one patients had adenocarcinoma of the prostate histopathologically (group 1). From these patients, the specimens were divided into two subgroups as specimens with malignant findings (group 1A) and specimens with benign findings (group 1B). The control group consisted of 31 patients with benign prostatic hyperplasia (group 2). In the specimens, the presence of mycoplasma DNA was investigated by the polymerase chain reaction method.

Results

The mycoplasma DNA was found to be positive in 11 (35.4 %) patients in group 1A and in 4 (12.9 %) patients in group 1B. There was no mycoplasma DNA in the patients in group 2. The differences between group 1A and group 1B, and between group 1A and group 2 were statistically significant (p values, respectively, 0.006 and 0.0001).

Conclusions

Our data supported the thesis that mycoplasma infections play a role in the etiopathogenesis of the prostate cancer.     

Can complexed prostate specific antigen enhance prostate cancer detection in Japanese men?

BACKGROUNDS: The aim of this study is to ascertain whether Bayer complexed PSA (cPSA) and volume referenced cPSA could enhance the detection of prostate cancer in Japanese men. METHODS: A total of 214 Japanese men whose serum total PSA (tPSA) values ranged from 1.2 ng/ml to 4600 ng/ml were enrolled from two institutions. Serum samples for tPSA, free PSA, PSA-alpha-1-antichymotripsin (PSA-ACT) and cPSA (ADVIA-Centaur) were obtained in all cases. In addition, total gland (TGV) as well as transition zone volume (TZV) were determined in all cases who underwent untrasound guided prostate biopsy (sextant and two additional transition zone biopsies). Biopsy outcome was correlated to the following parameters: tPSA, cPSA, PSA-ACT, free to total (F/T) PSA ratio, 2 complex to total (C/T) PSA ratios and 6 volume referenced parameters. RESULTS: Prostate cancer was detected in 85 of 214 patients (40%). The area under the receiver operating characteristic curve in non-volume referenced variables was highest for cPSA (0.736), followed by PSA-ACT (0.735), tPSA (0.722), F/T PSA ratio (0.613) and C/T PSA ratio (0.591). Comparing tPSA with the cutoff value of 4.0 ng/ml, the cutoff value with a 2.8 ng/ml of cPSA detected one more positive biopsy patient, decreasing one more cancer missed case and 8 more false positive cases. At sensitivities of 85% to 95% in men with tPSA between 4.00 and 10.00 ng/ml (n = 116), there were no significant differences in the corresponding specificities between tPSA and cPSA, or between cPSA and PSA-ACT. At sensitivities of 90% to 95%, the corresponding specificities of PSA-ACT adjusted for transition zone volume revealed best performance. As for the performance in men with a tPSA less than 4.0 ng/ml, the specificities of cPSA performed best, and differed significantly from PSA-ACT and F/T PSA at sensitivities of 80% to 90%. CONCLUSION: Bayer cPSA could replace the first screening test by total PSA and can enhance cancer detection, compared with PSA-ACT. However, cPSA did not provide additional value in differentiating cancer from non-cancer cases in men with a tPSA between 4.00 and 10.00 ng/ml.