Marco Raber

Trans-rectal Versus Trans-Perineal Saturation Rebiopsy of the Prostate: Is There a Difference in Cancer Detection Rate?

OBJECTIVE To test the hypothesis that there is no significant difference in the rate of prostate cancer (PCa) detection rate between the transrectal and transperineal approach in men undergoing a saturation (24-core) prostate rebiopsy. METHODS We evaluated 472 consecutive men who underwent a 24-core prostate rebiopsy at 2 tertiary referral centers. Of these, 70% (332) underwent a transrectal biopsy, and 30% (140) underwent a transperineal biopsy. Propensity score was used to match 280 patients with homogeneous characteristics; those represented the final study cohort. Univariable and multivariable logistic regression analyses were used to address the relationship between biopsy approach and PCa detection rate. Covariates consisted of age at biopsy, prostate-specific antigen, total prostate volume, digital rectal examination findings, histologic findings on previous biopsy, and the number of previous negative biopsy sets. RESULTS Overall, PCa detection rate was 28.6%. There was no statistically significant difference in PCa detection rate between the transrectal and transperineal approach (31.4% vs 25.7%, respectively; P = .3). The type of approach was not an independent predictor of PCa detection rate at multivariable analyses (odds ratio = 0.61, P = .1). CONCLUSIONS Transrectal and transperineal prostate saturation biopsies have a similar PCa detection rate in men undergoing a saturation rebiopsy. Both approaches can be offered to men undergoing a prostate rebiopsy without undermining the rate of PCa detection.

Multiple Vesico-Urethral Biopsies Following Radical Prostatectomy: The Predictive Roles of TRUS, DRE, PSA and the Pathological Stage

INTRODUCTION The aim of this study is to verify the predictive role of transrectal ultrasound (TRUS) of prostatic fossa, digital rectal examination (DRE), prostate specific antigen (PSA) and pathological stage after radical prostectomy in the detection of a prostate tumor recurrence at the level of the vesico-urethral anastomosis by means of multiple TRUS biopsies (6-8 cores). MATERIAL AND METHODS From October 1997, following a radical prostatectomy, 119 consecutive patients (median age: 67.9 years) with a PSA>or=0.2 ng/ml (median PSA: 0.9 ng/ml) underwent DRE and TRUS examinations with a 5.0-7.5 MHz variable frequency end-fire probe (Hitachi Medical System) and an EUB-525 machine. All patients received six TRUS-guided biopsies of the vesico-urethral anastomosis, and 1-2 additional biopsies directed to hypo-echoic or suspicious areas, if detected by TRUS. RESULTS Biopsies revealed recurrent carcinoma in 50% of patients (60/119). TRUS proved more sensitive than DRE (75% vs. 50%; p=0.01) and, conversely, DRE proved more specific than a TRUS (85% vs. 66%; p=0.03). Cancer was detected in 45% of the 34 patients with a PSA<or=0.5 ng/ml. In the group of patients with a PSA>or=2.0 ng/ml (24 patients), TRUS was able to detect every biopsy-proven local recurrence lesion (sensitivity: 100%). Conversely, all patients with a PSA>or=2.0 ng/ml and a negative TRUS had a negative biopsy (negative predictive value: 100%). In a multi-variable logistical analysis, the most predictive parameters determining a positive biopsy rate among those values studied (PSA, DRE, TRUS, positive surgical margins, pathological stage and time to PSA elevation) were TRUS and DRE findings (p=0.003, with an odds ratio of 4.6 and p=0.02, with an odds ratio of 4.1, respectively). CONCLUSION TRUS and TRUS biopsies utilizing 6-8 cores are efficient tools in the detection of local recurrence after a radical prostatectomy, even with a PSA<or=0.5 ng/ml. A combination of TRUS and DRE findings seems to predict biopsy results best. In case of a PSA>or=2.0 ng/ml and a negative TRUS, a biopsy of the vesico-urethral anastomosis could be avoided since the negative predictive value is 100%. Cancer recurrence detection seems to be predicted by TRUS and DRE findings, but not by PSA levels, pathological stage, status of the surgical margins or time to PSA elevation.

Initial Extended Transrectal Prostate Biopsy—Are More Prostate Cancers Detected With 18 Cores Than With 12 Cores?

PURPOSE We retrospectively investigated the detection rates of prostate cancer, high grade prostatic intraepithelial neoplasia and atypical glands suggestive of carcinoma by initial 18 and 12-core prostate biopsy. MATERIALS AND METHODS A total of 3,460 consecutive patients with prostate specific antigen between 2.5 and 15 ng/ml underwent 12 (1,684) or 18 (1,776) core prostate biopsy under local anesthesia at 2 departments that adopted the same indications for performing biopsy. Biopsies were evenly distributed throughout the prostate in 6 sectors. In the 12-core prostate biopsy group 2 samples were obtained from each sector and in the 18-core prostate biopsy group 1 additional core was taken from each sector. RESULTS The cancer detection rate in patients who underwent 18-core prostate biopsy was not different from the rate in those who underwent 12-core prostate biopsy (39.9% and 38.4%, p = 0.37), nor did the detection of atypical glands suggestive of carcinoma differ significantly between the 2 groups (2.9% and 3.3%, respectively, p = 0.33). However, 18-core prostate biopsy detected a significantly higher percent of cases of high grade prostatic intraepithelial neoplasia (20.0% vs 12.9%, p = 0.001). The cancer detection rate was higher with 18 than with 12-core prostate biopsy in patients with a prostate volume of 55 cc or greater (31.5% vs 24.8%, p = 0.01) but not in those with a prostate volume of less than 55 cc (54.3% and 53.0%, respectively, p = 0.7). Moreover, we determined that patients with positive digital rectal examination findings do not need 18-core prostate biopsy as opposed to 12-core prostate biopsy. CONCLUSIONS Compared with 12-core prostate biopsy, 18-core prostate biopsy detects significantly more cases of high grade prostatic intraepithelial neoplasia. However, 18-core prostate biopsy detects a significantly higher number of cancer only in patients with a prostate volume of 55 cc or greater.

Is extended and saturation biopsy necessary

Prostate biopsy (PBx) techniques have significantly changed since the original Hodges ‘sextant scheme’, which should now be considered obsolete. The feasibility of carrying out a biopsy scheme with a high number of cores in an outpatient setting is a result of the great improvement and efficacy of local anesthesia. Peri‐prostatic nerve block with lidocaine injection should be considered the ‘gold standard’ because it provides the best pain relief to patients undergoing PBx. The optimal extended protocol should now include the sextant template with an additional 4–6 cores directed laterally (anterior horn) to the base and medially to the apex. Saturation biopsies (i.e. template with ≥20 cores, including transition zone) should be carried out only when biopsies are repeated in patients where there is a high suspicion of prostate cancer. Complementary imaging methods (such as color‐ and power‐Doppler imaging, with or without contrast enhancement, and elastography) could be used in order to increase the accuracy of biopsy and reduce the number of unnecessary procedures. Nevertheless, the routine use of these methods is still under evaluation.

The Optimal Rebiopsy Prostatic Scheme Depends on Patient Clinical Characteristics: Results of a Recursive Partitioning Analysis Based on a 24-Core Systematic Scheme

BACKGROUND The most beneficial number and the location of prostate biopsies remain matters of debate, especially after an initial negative biopsy. OBJECTIVE To identify the optimal combination of sampling sites (number and location) to detect prostate cancer (PCa) in patients previously submitted to an initial negative prostatic biopsy. DESIGN, SETTING, AND PARTICIPANTS A transrectal ultrasound-guided systematic 24-core prostate biopsy (24PBx) was performed prospectively in 340 consecutive patients after a first negative biopsy (at least 12 cores). MEASUREMENTS We relied on a classification and regression tree analysis to identify three clinically different subgroups of patients at dissimilar risk of harboring PCa at second biopsy. Subsequently, we set the cancer-positive rate of the 24PBx at 100% and calculated PCa detection rates for 255 possible combinations of sampling sites. We selected the optimal biopsy scheme (defined as the combination of sampling sites that detected 95% of all the cancers with the minimal number of biopsy cores) for each patient subgroup. RESULTS AND LIMITATIONS After an initial negative biopsy, cancer was detected at rebiopsy in 95 men (27.9%). At a given number of cores, the cancer detection rates varied significantly according to the different combination of sites considered. Three different PCa risk groups were identified: (1) previous report of atypical small acinar proliferation of the prostate (ASAP), (2) no previous ASAP and ratio of free prostate-specific antigen (fPSA) to total PSA (%fPSA) ≤10%, and (3) no previous ASAP and %fPSA >10%. For patients with previous ASAP or patients with no previous ASAP and %fPSA ≤10%, two schemes with different combinations of 14 cores were most favorable. The optimal sampling in patients with no previous ASAP and %fPSA >10% was a scheme with a combination of 20 cores. CONCLUSIONS Both the number and the location of biopsy cores taken affect cancer detection rates in a repeated biopsy setting. We developed an internally validated flowchart to identify the most advantageous set of sampling sites according to patient characteristics.

Perianal and intrarectal anaesthesia for transrectal biopsy of the prostate: a prospective randomized study comparing lidocaine‐prilocaine cream and placebo

11 2 1 was already reported in two randomized clinical trials [3,4]. (ii) It is quite striking that all men in the placebo group completed the 12-core sampling; in the four-arm randomized trial by Galosi et al. [5], in 10% and 15% of patients in the placebo and notreatment group, respectively, the scheduled six-core biopsy session had to be prematurely interrupted due to intolerable pain, and in our series in 14% of the placebo group. The reason for this is probably the discrepancy in mean VAS score among the placebo groups of the studies, i.e. 1.6 during probe insertion and 3.2 during biopsy puncture in the series by Raber et al. [1], 5 (overall) in that reported by Basar et al. [4], and 5.5 (overall) in our series. The lower pain score in the series of Raber et al. might be due either to a less disturbing ultrasound probe or even to selection bias, but we are concerned about the representativity of the population, which could have consequently altered the real benefit of lidocaine-prilocaine anaesthesia. (iii) We agree with the authors that pain during prostate biopsy comes from both the insertion/residence of the TRUS probe into the anal canal and the biopsy punctures through the rectal mucosa, and we are convinced that the application of the anaesthetic cream should involve both locations. Accordingly, in our trial we first stratified the patients by discomfort/pain during simple TRUS at the initial clinical evaluation, and then randomized them to lidocaine-prilocaine or placebo for the subsequent prostate biopsy. Our analysis showed that in men with high compliance at TRUS, needle trauma did not significantly alter the tolerability, and that anaesthetic administration added little benefit for the subsequent biopsy; the opposite was found in patients with discomfort/pain of medium and high degree at initial TRUS, who benefited from local anaesthesia during the biopsy. On the contrary, stratification by age did not result in a statistically significant difference, unlike the result reported by Raber et al. Given that the studies so far addressing the issue of pain relief during prostate biopsy have resulted in controversial findings, as shown by many medical centres around the world still using or until recently using it routinely with no anaesthesia, we think that the anaesthesia should be reserved only for selected patients. These might be, e.g. the ‘younger’ ones ( < 67 years old), as suggested by Raber et al. , or those with high compliance (VAS score ≤ 2) to simple TRUS, as advised by us. Further studies aimed at seeking men potentially benefiting from pain control are, in our opinion, mandatory, before anaesthesia can be recommended as a standard procedure during prostate biopsy.

The role of transrectal saturation biopsy in tumour localization: pathological correlation after retropubic radical prostatectomy and implication for focal ablative therapy.

Study Type – Diagnostic (exploratory cohort)

ORIGINAL RESEARCH—EJACULATORY DISORDERS: Quantitative Sensory Testing of Peripheral Thresholds in Patients with Lifelong Premature Ejaculation: A Case-Controlled Study

INTRODUCTION The main functional factors related to lifelong premature ejaculation (PE) etiology have been suggested to be penile hypersensitivity, greater cortical penile representation, and disturbance of central serotoninergic neurotransmission. AIMS To quantitatively assess penile sensory thresholds in European Caucasian patients with lifelong PE using the Genito-Sensory Analyzer (GSA, Medoc, Ramat Yishai, Israel) as compared with those of an age-comparable sample of volunteers without any ejaculatory compliant. METHODS Forty-two consecutive right-handed, fully potent patients with lifelong PE and 41 right-handed, fully potent, age-comparable volunteers with normal ejaculatory function were enrolled. Each man was assessed via comprehensive medical and sexual history; detailed physical examination; subjective scoring of sexual symptoms with the International Index of Erectile Function; and four consecutive measurements of intravaginal ejaculatory latency time with the stopwatch method. All men completed a detailed genital sensory evaluation using the GSA; thermal and vibratory sensation thresholds were computed at the pulp of the right index finger, and lateral aspect of penile shaft and glans, bilaterally. MAIN OUTCOME MEASURES Comparing quantitatively assessed penile thermal and vibratory sensory thresholds between men with lifelong PE and controls without any ejaculatory compliant. RESULTS Patients showed significantly higher (P < 0.001) thresholds at the right index finger but similar penile and glans thresholds for warm sensation as compared with controls. Cold sensation thresholds were not significantly different between groups at the right index finger or penile shaft, but glans thresholds for cold sensation were bilaterally significantly lower (P = 0.01) in patients. Patients showed significantly higher (all P < or = 0.04) vibratory sensation thresholds for right index finger, penile shaft, and glans, bilaterally, as compared with controls. CONCLUSIONS Quantitative sensory testing analysis suggests that patients with lifelong PE might have a hypo- rather than hypersensitivity profile in terms of peripheral sensory thresholds. The peripheral neuropathophysiology of lifelong PE remains to be clarified.

Percent of Free Serum Prostate-Specific Antigen and Histological Findings in Patients Undergoing Open Prostatectomy for Benign Prostatic Hyperplasia

Purpose: To determine which pathologic features of the surgical specimen in men undergoing open prostatectomy for benign prostatic hyperplasia (BPH) correlate with preoperative and postoperative total, free prostate-specific antigen (PSA) levels and the free-to-total PSA ratio. Methods: Forty-four patients, undergoing open prostatectomy for BPH without evidence of prostate cancer in systematic biopsies and clinical prostatitis, were included in this prospective study. Each prostatectomy specimen was weighed and each slide was evaluated for inflammation (acute prostatitis, chronic-active prostatitis and chronic-inactive prostatitis), prostatic intraepithelial neoplasia, transitional/squamous metaplasia, cystic ductal dilation, leiomyoma-resembling stromal cell proliferation, leakage of prostatic secretion, infarction and prostatic calculi. Results: The mean preoperative (and postoperative) total PSA and free PSA levels were 6.1 ± 4.3 (1.14 ± 0.87) and 1.7 ± 1.6 (0.24 ± 0.19) ng/ml, respectively. The mean prostatic and transition zone volume was 83.9 ± 28.4 and 55.4 ± 27.6 cm3, respectively. Both total PSA and free PSA levels were correlated with total gland volume (p = 0.0001; p = 0.002) and the volume of the surgical specimen (p = 0.003; p < 0.05) and, upon stepwise logistic analysis, patients with a total gland volume of <50 cm3 had an odds ratio of 11 (CI 1.6–71.3) for having a free-to-total ratio of <18%. No minimal change pathology or prostatic inflammation were associated with preoperative total or free PSA levels. The free-to-total PSA ratio was higher in the group of patients with histologically acute and moderate to severe chronic-active prostatitis (mean ratio 27 ± 12%) than in patients with chronic-inactive prostatitis and minimal chronic-active prostatitis (mean ratio 0.19 ± 13%; p = 0.05), showing an odds ratio of 5 (CI 1.1–22.1) for having a free-to-total PSA ratio of <18%. Conclusions: Prostate volume and, in particular, transition zone volume seem to influence both free and total PSA levels in men with BPH. The free-to-total PSA ratio seems to be influenced by the presence of histological prostatitis in the surgical specimen. In particular, patients with a prostate volume of <50 cm3 and an inactive form of prostatitis seem to have a relatively higher risk of having a free-to-total PSA ratio of <18%.

Unilateral positive biopsies in low risk prostate cancer patients diagnosed with extended transrectal ultrasound-guided biopsy schemes do not predict unilateral prostate cancer at radical prostatectomy

Study Type – Diagnostic (exploratory cohort)