Cancer detection rates and inter-examiner variability of MRI/TRUS fusion targeted biopsy and systematic transrectal biopsy.

BACKGROUND: Software-based MRI/TRUS fusion biopsy depends on the coordination of several steps, and inter-examiner differences could influence the results. The aim of this bicentric prospective study was to compare the detection rates of MRI/TRUS fusion targeted biopsy (TG) and systematic biopsy (SB), and the detection rates of examiners with different levels of previous experience in prostate biopsy. METHODS: A total of 419 patients underwent MRI based on a suspicion of prostate cancer with elevated PSA levels. MRI was positive in 395 patients (221 in the first biopsy group [FB] and 174 in the repeated biopsy group [RB]). A subsequent TG, followed by a SB, was performed on these patients by four different examiners. RESULTS: In the detection of clinically significant prostate cancer, a significant difference was found for TG+SB against SB in the RB group (35.1% vs. 25.3%, P=0.047). In the detection of clinically insignificant prostate cancer, the SB had a significantly higher detection rate than TG in both subgroups (FB: 11.9% vs. 4.7%, P=0.008; RB: 13.8% vs. 6.9%, P=0.034). A significant difference was found between the four examiners in the FB for TG (P=0.028), SB (P=0.036), and TG+SB (P=0.017). CONCLUSION: MRI/TRUS TG in combination with SB had significantly higher detection rates than SB in the RB group only. Differences in detection rates between examiners were dependent on the level of previous experience with TRUS guided biopsy.

Use of Prostate Specific Antigen Density Combined with Multiparametric Magnetic Resonance Imaging Improves Triage for Prostate Biopsy.

BACKGROUND: Multi-parametric magnetic resonance imaging (mpMRI)-directed biopsy for prostate cancer (PC) diagnosis improves the detection of clinically significant prostate cancer (CSPC) and decreases the rate of over-diagnosis of insignificant disease. The aim of this study was to investigate the value of mpMRI combined with prostate specific antigen density (PSAD) in the decision making related to the biopsy. METHODS: mpMRI and mpMRI/transrectal ultrasound fusion targeted biopsies with subsequent systematic biopsies were performed in 397 patients (223 biopsy-naïve and 174 with a previous biopsy). Detection rates of (CSPC) and insignificant PC were stratified using the PIRADS score, and the number of avoidable biopsies and missed (CSPC) were plotted against PSAD values of 0.1-0.5 ng/mL2. RESULTS: PIRADS <3 and PSAD <0.2 ng/mL2 were the safest criteria for not performing a biopsy. When applied to the biopsy-naïve group, 21.5% (48/223) of the biopsies could have been avoided and 3.7% (3/82) of CSPC would have been missed. In the repeat biopsy group, 12.6% (22/174) of biopsies could have been avoided and 6.9% (4/58) of (CSPC) would have been missed. CONCLUSIONS: A combination of mpMRI and PSAD might reduce the number of biopsies performed with the cost of missing <4% of CSPC.

The meaning of sampling density in multiple repeat prostate biopsies.

INTRODUCTION: Extended transrectal ultrasound-guided prostate biopsy is a state-of-the-art tool for prostate cancer detection. Nevertheless, approximately 1/3 of cancers are missed when using this method and repeat biopsy sessions are often required. The aim of this study was to investigate how sampling density (a compound variable reflecting the number of biopsy cores and prostate volume) impacts on detection rate in multiple repeat TRUS-biopsies. MATERIAL AND METHODS: A total of 1007 consecutive patients undergoing their 1st, 2nd, 3rd and any further repeat prostate biopsies were included. The relationship between sampling density and other clinical variables (age, prostate-specific antigen level, free/total PSA ratio, digital rectal examination, number of previous biopsies) and cancer detection rate were assessed by interaction analysis. RESULTS: There were 562 primary re-biopsies, 267 second re-biopsies and 178 third and further re-biopsies included in the study. Detection rate was 25.4%, 25.8% and 25.3%, respectively. Interaction of sampling density with age was demonstrated in patients undergoing their first repeat biopsy (but not further re-biopsies). No interaction was observed with other variables investigated. CONCLUSIONS: A more extensive prostate sampling leads to a higher cancer detection rate on repeat prostate biopsies, as shown previously. However, this effect seems to be particularly pronounced in men younger than 65 years undergoing their first repeat prostate biopsy.

External validation of extended prostate biopsy nomogram.

INTRODUCTION: Historical nomograms for the prediction of cancer on prostate biopsy, developed in the sextant biopsy era are no more accurate today. The aim of this study was an independent external validation of a 10-core biopsy nomogram by Chun et al. (2007). MATERIAL AND METHODS: A total of 322 patients who presented for their initial biopsy in a tertiary care center and had all the necessary data available were included in the retrospective analysis. To validate the nomogram, receiver operator characteristic (ROC) curves and calibration plots were constructed. RESULTS: Area under the ROC curve calculated for our data using the nomogram was 0.773, similar to that reported originally. However, the nomogram systematically overestimated prostate cancer risk, which, for our data, could be resolved by subtracting 24 points from the total number of points of the nomogram. CONCLUSIONS: The nomogram yielded overall good predictive accuracy as measured by the area under the ROC curve, but it systematically overestimated PC probability in individual patients. However, we showed how the nomogram could easily be adapted to our patient sample, resolving the bias issue.

Regulatory T cells, dendritic cells and neutrophils in patients with renal cell carcinoma.

We evaluated dendritic cells (DC), regulatory T lymphocytes (Treg) and neutrophils in 37 patients with newly diagnosed renal cell carcinoma (RCC) in the tumor and peripheral blood (PB) and correlated these parameters with tumor staging (early-T1, 2, late-T3, 4 and metastatic disease). The number of myeloid and plasmacytoid DC in blood of RCC patients was higher than in healthy controls. The percentage of myeloid dendritic cells (mDC) from CD45+ cells in tumors was higher in comparison with peripheral blood irrespective of disease stage. Higher percentage of these cells expressed a maturation marker in the periphery in the early stage (CD83 expressing cells). The number of plasmacytoid dendritic cells (pDC) in PB was similar in both early and late stage groups, but the early group displayed a significantly higher percentage of pDC in tumor cell suspension. Neutrophil counts in the peripheral blood of RCC patients were higher than in healthy controls, but the counts in both tumor stage groups were similar. The proportion of neutrophils from CD45+ cells was higher in late stage tumors. Higher percentage of Treg from CD4+ cells was detected in renal carcinoma tissue in comparison to PB with no difference between stages of the disease. Our results reflect the complex interplay between various cells of the immune system and the tumor microenvironment. Activation of dendritic cell subpopulations at early stages of the disease course is counterbalanced by the early appearance of T regulatory cells both in the periphery and tumor tissue. Later stages are characterized by the accumulation of neutrophils in the tumor. Appropriate timing of anticancer strategies, especially immunotherapy, should take these dynamics of the immune response in RCC patients into account.

Parameters derived from the postoperative decline in ultrasensitive PSA improve the prediction of radical prostatectomy outcome.

PURPOSE: Contemporary tools estimating increased risk of prostate cancer (PCa) relapse after radical prostatectomy (RP) are far from perfect and there has been an intensive search for additional predictive variables. We aimed to explore whether the parameters of postoperative ultrasensitive prostate-specific antigen (PSA) decline provide additional information for predicting PCa progression. METHODS: A total of 319 consecutive men, with at least 2 years of follow-up after RP for clinically localized PCa were subjected to this study. Intensive postoperative measurements of ultrasensitive PSA resulted in total of 4028 PSA values available for statistical evaluation. Biochemical recurrence (BCR) was defined as PSA ≥0.2 ng/ml. The accuracy of predictive models was quantified with the area under the curve. RESULTS: Over a median follow-up of 43 months (24-99 months), 107 patients (34%) experienced BCR after RP. In patients with BCR, significantly higher values of PSA nadir (p < 0.001) and a decreased time interval from surgery to reach PSA nadir (p < 0.001) were observed. A multivariable Cox regression model confirmed that PSA nadir >0.01 ng/ml (HR 6.01, 95% CI: 3.89-9.52) and time to PSA nadir <3 months (HR 2.86, 95% CI: 1.74-5.01) were independent predictors of BCR. The inclusion of PSA nadir and the time to PSA nadir into the model resulted in improvement of predictive accuracy by 16% over the model designed on the basis of established parameters. CONCLUSIONS: Our results demonstrate that the level of PSA nadir and the time to PSA nadir determined by ultrasensitive assay significantly improve the identification of patients who are at high risk of disease recurrence after RP.

FOCUS on FOCIS: combined chemo-immunotherapy for the treatment of hormone-refractory metastatic prostate cancer.

Immunotherapy has emerged as another treatment modality in cancer. The goal of immunotherapy in advanced cancer patients does not have to be the complete eradication of tumor cells but rather the restoration of a dynamic balance between tumor cells and the immune response. Appropriate combination of tumor mass reduction (by surgery and/or chemotherapy) and neutralization of tumor-induced immunosuppression might set the right conditions for the induction of anti-tumor immune response by active immunotherapy. We review experimental basis and key concepts of combined chemo-immunotherapy and document its principles in the case report of patient with hormone refractory metastatic prostate cancer with sinister prognosis. More than four hundred prostate cancer patients have been treated with DC-based immunotherapy and tumor-specific immune responses have been reported in two-thirds of them. In half of these patients, DC immunotherapy resulted in transient clinical responses. Tregs, among other factors, potently inhibit tumor-specific T cells. Prostate cancer patients have elevated numbers of circulating and tumor infiltrating Tregs and there is evidence that Tregs increase tumor growth in vivo. Because of the high frequency of circulating Tregs in our patients, we first administered metronomic cyclophosphamide. After obtaining IRB approval, we started regular vaccinations with dendritic cells (DCs) loaded with killed prostate cancer cells. In accordance with the principles of combined immunotherapy, we continued palliative chemotherapy with docetaxel to reduce the tumor cell burden. DC-based vaccination induced prostate cancer cell-specific immune response. Combined chemo-immunotherapy consisting of alternate courses of chemotherapy and vaccination with mature DCs pulsed with LNCap prostate cancer cell line led to the marked improvement in the clinical and laboratory presentation and to the decrease of PSA levels by more than 90%.

In vitro assessment of dendritic cells pulsed with apoptotic tumor cells as a vaccine for ovarian cancer patients.

Surgery and chemotherapy are standard treatments in ovarian cancer, but patients have a high rate of relapse. Dendritic cell (DC)-based vaccines are a new treatment option for elimination of residual tumor disease. We aim to explore the feasibility and immunogenicity of DC vaccines pulsed with autologous irradiated tumor cells from ovarian cancer patients. Monocyte-derived DC were generated and pulsed with autologous tumor-derived bodies, matured and subsequently cocultured with autologous lymphocytes. The ability of DC to activate lymphocytes was evaluated by proliferation and IFN-gamma ELISPOT. Induction of tumor cell apoptosis was optimal at 24 h, and DC pulsing optimal at 4 h. Maturation of DC and proliferation of lymphocytes were achieved in 75% of patients tested. Lymphocyte IFN-gamma production increased in response to tumor antigen-pulsed DC. We show the feasibility of preparing individual DC-based vaccines in ovarian cancer patients and the potential for induction of lymphocyte responses.