Pietro Pepe

Prostate Needle Biopsy: 12 vs. 18 Cores – Is It Necessary?

Introduction: The aim of this study is to compare the histological results of a prostate needle biopsy scheme of 12 and 18 cores used in 372 consecutive patients submitted to an early stage diagnosis programme for prostate cancer (PCa). Materials and Methods: From February 2002 to July 2003 a transperineal TRUS-guided prostate needle biopsy was performed in 372 patients aged 40–73. Indications for biopsy were: suspected DRE, total PSA (PSAt) >10 ng/ml; PSAt equal to 4–10, 2.6–3.9, ≤2.5 ng/ml and PSA F/T <25%, <20% and <15%, respectively. In 256 patients, we performed 12 cores and in 116 cases 18 cores. Results: 159 (42.7%) patients were diagnosed with PCa, 138 (37%) with BPH, 58 (15.7%) with chronic prostatitis, 15 (4%) with a HGPIN, 2 (0.6%) with ASAP. In patients that underwent 12 and 18 cores the incidence of PCa was 39.8 and 49%; the incidence of PCa in patients with PSA ≤10 and >10 ng/ml submitted to 12 and 18 cores was 35 vs. 47% and 57.8 vs. 52%, respectively. The preponderance of clinical stage T1c was 50% (12 cores) vs. 72% (18 cores). The median bioptic Gleason score in both groups resulted 6.6 (12 cores) and 6 (18 cores). In 110 (12 bioptic cores) and in 30 (18 bioptic cores) patients that underwent a RRP, the pTNM proved a significant clinical neoplasm (Gleason score ≧6 and/or tumoral volume >0.5 cm3) in the first group in all cases, while in the second group in 28/30 (94%) cases. Conclusions: Extended schemes of prostate needle biopsy of 18 or more cores increases the PCa diagnosis in early stage and should be adopted for young patients with a PSA <10 ng/ml, negative DRE and in case of rebiopsies.

Incidence of insignificant prostate cancer using free/total PSA: results of a case-finding protocol on 14,453 patients.

To evaluate prostate cancer (PCa) detection and incidence of pathologically insignificant PCa (pIPCa) tumour using percent-free PSA (%f-PSA) in patients with total PSA ⩽10 ng ml−1. From February 2002 to October 2009, 14 453 patients (median 60.5 years) were enrolled in a case-finding protocol for the early diagnosis of PCa. Indications to biopsy were suspicious digital rectal examination; PSA >10 ng ml−1; PSA⩽2.5 ng ml−1, included between 2.6–4 and 4.1–10 ng ml−1 with %f-PSA <15, <20 and <25%, respectively. A median of 18 and 26 cores in case of primary and repeated biopsy were determined; 2123 men underwent prostate biopsy, of whom 1589 (74.8%) had a PSA ⩽10 ng ml−1. A PCa was found in 777 (36.6%) and in 35 (23.3%) patients at primary and repeated biopsy: 459 and 26 men had PSA ⩽10 ng ml−1 and 419 and 26 patients underwent surgery, respectively, 244 (58.3%) and 18 (69.2%) had an organ-confined PCa with a pIPCa incidence equal to 1.4 and 7.7%, respectively. Cancer detection rate of 28.8% in patients with PSA ⩽10 ng ml−1 associated with a low incidence of pIPCa should induce to introduce %f-PSA in screening programmes to reduce the risk of overdiagnosis.

Management of severe blunt renal trauma in adult patients: a 10-year retrospective review from an emergency hospital.

Study Type – Therapy (case series)

Can 3-Tesla pelvic phased-array multiparametric MRI avoid unnecessary repeat prostate biopsy in patients with PSA < 10 ng/mL?

INTRODUCTION The aim of this study was to evaluate multiparametric pelvic magnetic resonance imaging (mpMRI) accuracy in prostate cancer (PCa) diagnosis. PATIENTS AND METHODS From June 2011 to March 2014, 100 patients (median age, 64 years) with negative digital rectal examination underwent repeat transperineal saturation biopsy (SPBx; median, 29 cores) for persistent prostate-specific antigen (PSA) values between 4.1 and 10 ng/mL with free/total PSA ≤ 25%. All patients underwent mpMRI using a 3.0-Tesla scanner (ACHIEVA; Philips) equipped with surface 16 channels phased-array coil and lesions suspicious for PCa were submitted to additional targeted biopsies. RESULTS A T1c PCa was found in 37 (37%) of cases; SPBx and mpMRI targeted biopsy diagnosed 34 (34%) and 29 (29%) cancers, missing 3 (all of the anterior zone) and 8 cancers (7 and 1 of the lateral margins and anterior zone, respectively); in detail, mpMRI missed 8 (21.7%) PCa characterized by minimal histological disease at risk for insignificant cancer. The diameter of the mpMRI suspicious lesion was significantly correlated with the diagnosis of PCa with poor Gleason score (P = .005). The detection rate of cancer for each mpMRI core was 40.7%; moreover, mpMRI would have spared 31 (31%) unnecessary SPBx. Diagnostic accuracy, sensitivity, specificity, and positive and negative predictive value of mpMRI in diagnosing overall cancer versus significant PCa was 82.6% versus 81.3%, 82.2% versus 100%, 77.8% versus 78.9%, 65.4% versus 55.8%, and 95.5% versus 100%, respectively. CONCLUSION mpMRI targeted biopsy improved diagnosis of significant anterior zone PCa, missing cancers at risk for clinically insignificant disease; moreover, the diameter of the lesion on mpMRI was significantly predictive of aggressive PCa.

Should Men with Serum Prostate-Specific Antigen ≤4 ng/ml and Normal Digital Rectal Examination Undergo a Prostate Biopsy?

The clinical significance of a prostate cancer (PCa) cannot be determined solely by tumor volume (≤0.5 cm3), 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.

Poly (ADP-ribose) Polymerase 1 Protein Expression in Normal and Neoplastic Prostatic Tissue

A genetic background has been implicated in the development of prostate cancer. Protein microarrays have enabled the identification of proteins, some of which associated with apoptosis, that may play a role in the development of such a tumor. Inhibition of apoptosis is a co-factor that contributes to the onset and progression of prostate cancer, though the molecular mechanisms are not entirely understood. Poly (ADP-ribose) polymerase 1 (PARP-1) gene is required for translocation of the apoptosis-inducing factor (AIF) from the mitochondria to the nucleus. Hence, it is involved in programmed cell death. Different PARP-1 gene expression has been observed in various tumors such as glioblastoma, lung, ovarian, endometrial, and skin cancers. We evaluated the expression of PARP-1 protein in prostatic cancer and normal prostate tissues by immunohistochemistry in 40 men with prostate cancer and in 37 normal men. Positive nuclear PARP-1 staining was found in all samples (normal prostate and prostate cancer tissues). No cytoplasmic staining was observed in any sample. PARP-1-positive cells resulted significantly higher in patients with prostate carcinoma compared with controls (P<0.001). PARP-1 over-expression in prostate cancer tissue compared with normal prostate suggests a greater activity of PARP-1 in these tumors. These findings suggest that PARP-1 expression in prostate cancer is an attempt to trigger apoptosis in this type of tumor similarly to what reported in other cancers.

Detection Rate of Anterior Prostate Cancer in 226 Patients Submitted to Initial and Repeat Transperineal Biopsy

Objective: To evaluate the detection rate of anterior zone (AZ) prostate cancer (PCa) in patients submitted to initial and repeat transperineal prostate biopsy. Methods: From January 2013 to August 2013, 226 patients (median age 64 years) with negative digital rectal examination underwent initial (144 cases) and repeat (82 cases) transperineal prostate biopsy for PSA >10 ng/ml, PSA 4.1-10.0 or 2.6-4.0 ng/ml with free/total PSA ≤25% and ≤20%, respectively. A median of 22 versus 32 cores were performed, including 4 cores of the AZ versus 6 cores (4 anterior plus 2 cores of the transition zone, TZ) at initial versus repeat biopsy, respectively. The detection rate of PCa of the peripheral zone (PZ), AZ and TZ was prospectively evaluated. Results: The median PSA was 7.6 ng/ml; overall, a stage cT1c PCa was found in 104/226 (46%) patients, in 70 (48.6%) and 34 (41.5%) of the men who underwent initial and repeat biopsy, respectively. An AZ PCa was found in 11.5 vs. 8.8% (p = 0.32) of the patients submitted to initial versus repeat biopsy, respectively. AZ cancers demonstrated a number of positive cores (p = 0.03), greatest percentage of cancer (p = 0.001) and total percentage of cancer (p = 0.001) significantly lower in comparison with PZ PCa; moreover, 56.2 vs. 36.5% of AZ versus PZ PCa were characterized by a microfocus of cancer (p = 0.001), respectively. Conclusions: AZ biopsies increase the detection rate of PCa (about 10% of cases) at initial and repeat biopsy, allowing reduction of the biopsy false-negative rate.

Does an Inflammatory Pattern at Primary Biopsy Suggest a Lower Risk for Prostate Cancer at Repeated Saturation Prostate Biopsy

Introduction: To evaluate if an inflammatory pattern at primary biopsy is associated with a lower risk for cancer in men submitted to repeated saturation prostate biopsy (SPBx). Methods: From January 2005 to January 2010, 320 patients, after a negative primary extended biopsy (median 18 cores), underwent SPBx by transperineal approach performing 27 cores (median). 210 (65.6%) patients had a normal parenchyma and 110 had an inflammatory pattern (34.4%) at primary biopsy (none of them complained of symptoms suggesting a diagnosis of acute prostatitis at the time of biopsy). Moreover, median prostate-specific antigen and abnormal digital rectal examination was equal to 7.3 ng/ml and 3.6% versus 8.2 ng/ml and 3.8%, respectively. Results: Prostate cancer (PCa) was found in 66 (20.5%) of 320 patients. Of these, 42 (63.6%) and 24 (36.4%; p = 0.007) had a histological diagnosis of chronic prostatitis and normal parenchyma at primary biopsy, respectively. Conclusions: An inflammatory pattern at primary biopsy is not associated with a decrease in PCa incidence at repeated SPBx; therefore, only an accurate clinical evaluation including more parameters (i.e. urinary PCA3) could hopefully select men who need to undergo rebiopsy in the presence of persistent suspicion of cancer.

Does the adjunct of ecographic contrast medium Levovist improve the detection rate of prostate cancer

Objectives: To evaluate whether the adjunct of an ultrasound contrast medium improves the detection rate of prostate cancer.Method: In 34 patients, scheduled to undergo a trans-perineal extended prostate biopsy, we carried out a color-Doppler ultrasound (CDU) of the prostate before and after i.v. injection of Levovist®, an ultrasound contrast medium. Further bioptic samples were taken in the areas where a marked increase in vascularization was noticed.Results: The overall diagnostic sensitivity, specificity and efficiency were respectively 72.7, 56.2 and 62.9% for transrectal ultrasound (TRUS); 80, 56.2 and 65.3% for CDU and 88.8, 54.5 and 68% for CDU after Levovist® injection; 66.5, 72.6 and 65.1% for digito-rectal examination (DRE); 100, 51.4 and 65.4% for total PSA; and 100, 88.8 and 94.3% for PSA free/total. In the 16 patients with prostate carcinoma, the sensitivity of CDU after Levovist® was 92.3, 66% for both DRE and TRUS, and 80% for DRE plus TRUS.Conclusions: Considering the cost and the results obtained (high sensitivity and low specificity), a routine use of Levovist® does not seem indicated in patients undergoing prostatic biopsy. An exception may be represented by patients with both negative DRE and TRUS.

Is a single focus of low-grade prostate cancer diagnosed on saturation biopsy predictive of clinically insignificant cancer?

Objectives: To evaluate the incidence of indolent prostate cancer (PCa; <0.5 ml cancer and Gleason score, GS, ≤6) in men with microfocal PCa diagnosed on saturation biopsy (SPBx) submitted to radical retropubic prostatectomy. Methods: From January 2005 to December 2008, 413 patients (median age 61.5 years) underwent SPBx (median 30 cores). A single neoplastic microfocus (5% or less of cancer in a single core) was found in 55 men and all patients underwent retropubic prostatectomy. Median PSA was equal to 8.2 ng/ml, digital rectal examination was negative and GS was 6 in 40 cases and not evaluable in 15 cases. Results: Prostatectomy specimens showed a significant cancer in 48/55 (87.3%) patients with a median GS of 6.2 (range 5–8), presence of extraprostatic extension and positive surgical margins in 15 (27.3%) and 8 (14.5%) cases, respectively. Six patients had an indolent PCa, and in 1 case no tumor was found. Conclusions: Patients with a single microfocal PCa diagnosed on SPBx corresponded to an insignificant cancer in surgical specimens only in 12.7% of cases, but they should be informed that they may harbor more aggressive disease with a risk of non-organ-confined cancer that in our series was 27.3%.