Carmen Maccagnano

Prostate-Specific Antigen (PSA) Isoform p2PSA Significantly Improves the Prediction of Prostate Cancer at Initial Extended Prostate Biopsies in Patients with Total PSA Between 2.0 and 10 ng/ml: Results of a Prospective Study in a Clinical Setting

BACKGROUND Total prostate-specific antigen (tPSA), ratio of free PSA (fPSA) to tPSA (%fPSA), and PSA density (PSAD) testing have a very low accuracy in the detection of prostate cancer (PCa). There is an urgent need for more accurate biomarkers. OBJECTIVE To compare the diagnostic accuracy of PSA isoform p2PSA and its derivatives in determining the presence of PCa at initial biopsy with the accuracy of other predictors in patients with tPSA 2.0-10 ng/ml. DESIGN, SETTING, AND PARTICIPANTS We conducted an observational prospective study in a real clinical setting of consecutive men with tPSA 2.0-10 ng/ml and negative digital rectal examination who were scheduled for prostate biopsy at a tertiary academic center. INTERVENTION Outpatient transrectal ultrasound-guided prostate biopsies were performed according to a standardized institutional saturation scheme (18-22 cores). MEASUREMENTS We determined the diagnostic accuracy of serum tPSA, %fPSA, PSAD, p2PSA, %p2PSA [(p2PSA/fPSA)×100] and the Beckman Coulter Prostate Health Index (phi; [p2PSA/fPSA×√tPSA]). RESULTS AND LIMITATIONS Overall, 107 of 268 patients (39.9%) were diagnosed with PCa at extended prostate biopsies. Statistically significant differences between patients with and without PCa were observed for age, prostate and transition zone volume, PSAD, %p2PSA, and phi (all p values<0.05). In univariate accuracy analysis, phi and %p2PSA were the most accurate predictors of PCa (area under the curve: 75.6% and 75.7%, respectively), followed by transition zone volume (66%), prostate volume (65%), patient age (63%), PSAD (61%), %fPSA (58%), and tPSA (53%). In multivariate accuracy analyses, both phi (+11%) and %p2PSA (+10%) significantly improved the accuracy of established predictors in determining the presence of PCa at biopsy (p<0.001). Although %p2PSA and phi were significantly associated with Gleason score (Spearman ρ: 0.303 and 0.387, respectively; p ≤ 0.002), they did not improve the prediction of Gleason score ≥7 PCa in multivariable accuracy analyses (p > 0.05). CONCLUSIONS In patients with a tPSA between 2.0 and 10 ng/ml, %p2PSA and phi are the strongest predictors of PCa at initial extended biopsies and are significantly more accurate than the currently used tests (tPSA, %fPSA, and PSAD) in determining the presence of PCa at biopsy.

Role of imaging and biopsy to assess local recurrence after definitive treatment for prostate carcinoma (surgery, radiotherapy, cryotherapy, HIFU)

PurposeDefining the site of recurrent disease early after definitive treatment for a localized prostate cancer is a critical issue as it may greatly influence the subsequent therapeutic strategy or patient management.MethodsA systematic review of the literature was performed by searching Medline from January 1995 up to January 2011. Electronic searches were limited to the English language, and the keywords prostate cancer, radiotherapy [RT], high intensity focused ultrasound [HIFU], cryotherapy [CRIO], transrectal ultrasound [TRUS], magnetic resonance [MRI], PET/TC, and prostate biopsy were used.ResultsDespite the fact that diagnosis of a local recurrence is based on PSA values and kinetics, imaging by means of different techniques may be a prerequisite for effective disease management. Unfortunately, prostate cancer local recurrences are very difficult to detect by TRUS and conventional imaging that have shown limited accuracy at least at early stages. On the contrary, functional and molecular imaging such as dynamic contrast-enhanced MRI (DCE–MRI), and diffusion-weighted imaging (DWI), offers the possibility of imaging molecular or cellular processes of individual tumors.Recently, PET/CT, using 11C-choline, 18F-fluorocholine or 11C-acetate has been successfully proposed in detecting local recurrences as well as distant metastases. Nevertheless, in controversial cases, it is necessary to perform a biopsy of the prostatic fossa or a biopsy of the prostate to assess the presence of a local recurrence under guidance of MRI or TRUS findings.ConclusionIt is likely that imaging will be extensively used in the future to detect and localize prostate cancer local recurrences before salvage treatment.

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.

Ureteral endometriosis: Proposal for a diagnostic and therapeutic algorithm with a review of the literature

Introduction: The ureteral involvement in deep pelvic endometriosis in usually asymptomatic and might lead to a silent loss of renal function. As a matter of fact, the diagnosis and the treatment modalities are still a matter of debate. Materials and Methods: We performed a literature review by searching the MEDLINE database for articles published in English between 1996 and 2010, using the key words urinary tract endometriosis, ureteral endometriosis, diagnosis and treatment. We found more than 200 cases of ureteral endometriosis (UE). Results: The disease most commonly affects a single distal segment of the ureter, with a left predisposition in most of the patients. Two major pathological types of UE may be distinguished: intrinsic and extrinsic. The symptoms are usually nonspecific and owing to secondary obstruction. The diagnosis has to be considered as a step- by-step procedure, starting from physical examination to highly detailed imaging methods. Nowadays, the treatment is usually chosen according to the type of UE, the site lesion and the distance to the ureteral orifice, with the use of JJ stents remaining a matter of debate. Conclusions: A close collaboration between the gynecologist and the urologist is advisable, especially in referral centers. Surgical treatment can lead to good results in terms of both patient compliance and prognosis.

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.

Diagnosis and Treatment of Bladder Endometriosis: State of the Art

Background: The bladder is the most common affected site in urinary tract endometriosis, being diagnosed during gynecologic follow-up. The surgical urological treatment might lead to good results. Study Objective: To define the state of the art in the diagnosis and treatment of bladder endometriosis. Methods: We performed a literature review by searching the MEDLINE database for articles published between 1996 and 2011, limiting the searches to the words: urinary tract endometriosis, bladderendometriosis, symptoms, diagnosis and treatment.Results: Deep pelvic endometriosis usually involves the urinary system, with the bladder being affected in 85% of cases. The diagnosis has to be considered as a step-by-step procedure. Currently, the treatment is usually surgical, consisting of either transurethral resection or partial cystectomy, and eventually associated with hormonal therapy. The hormonal therapy alone counteracts only the stimulus of endometriotic tissue proliferation, with no effects on the scarring caused by this tissue. The overall recurrence rate is about 30% for combined therapies and about 35% for the hormonal treatment alone. Conclusions: The bladder is the most common affected site in urinary tract endometriosis. Most of the time, this condition is diagnosed because of the complaint of urinary symptoms during gynecologic follow-up procedures for a deep pelvic endometriosis: a close collaboration between the gynecologist and the urologist is advisable, especially in highly specialized centers. The surgical urological treatment might lead to good results in terms of patients’ compliance and prognosis.

Clinical Reliability of the 2004 WHO Histological Classification System Compared With the 1973 WHO System for Ta Primary Bladder Tumors

PURPOSE Histopathological grade remains the most important predictive factor for the prognosis of nonmuscle invasive bladder cancer. We defined the clinical reliability of the 2004 WHO and International Society of Urological Pathology histological classification system compared with that of the 1973 WHO system for Ta primary bladder tumors. MATERIALS AND METHODS We evaluated 270 consecutive patients with a first episode of low grade pTa bladder cancer at transurethral resection of the bladder between 2004 and 2008. Grade was assigned by a single uropathologist simultaneously as low grade, and as G1 or G2 according to the 2004 and 1973 WHO classification systems, respectively. All patients received a single early prophylaxis instillation of 50 mg epirubicin as the only adjuvant treatment. Followup included urine cytology and cystoscopy 3 months after resection and every 6 months thereafter for 5 years. Univariate and multivariate analysis of recurrence-free and progression-free survival was done with the Kaplan-Meier method and the log rank test. RESULTS Mean patient age was 67.3 years (median 67, range 27 to 91). Of the patients 50 were female (18.1%) and 220 (81.9%) were male. According to the 1973 system, grade was G1 in 87 patients (32.2%) and G2 in 183 (67.8%). Median followup was 25 months (mean 27.4, range 3 to 72). The 5-year recurrence-free survival rate was 49.4% for the low grade population, and 62% and 40% for the G1 and G2 groups, respectively (p = 0.004). The 5-year progression-free survival rate was 93% for the low grade population, and 97.6% and 93.3% for the G1 and G2 groups, respectively (p = 0.06). CONCLUSIONS The 1973 WHO classification system predicted the risk of recurrence in primary pTa cases more accurately than the 2004 WHO system. Each classification had the same accuracy when predicting the risk of progression. Our study confirms the clinical reliability of the new histological classification in clinical practice from a prognostic point of view.

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)

Prostate Saturation Biopsy following a First Negative Biopsy: State of the Art

Introduction: Saturation prostate biopsy (SPBx) has been initially introduced to improve prostate cancer (PCa) detection rate (DR) in the repeat setting. Nevertheless, the optimal number and the most appropriate location of the cores, together with the timing to perform a second PBx and the eventual modification of the PBx protocols according to the different clinical situations, are matters of debate. The aim of this review is to perform a critical analysis of the literature about the actual role of SPBx in the repeat setting. Materials and Methods: We performed a systematic review of the literature since 1995 up to 2011. Electronic searches were limited to the English language, using the MEDLINE database. The key words ‘saturation prostate biopsy’ and ‘repeated prostate biopsy’ were used. Results: SPBx improves PCa DR if clinical suspicion persists after previous biopsy with negative findings and provides an accurate prediction of prostate tumor volume and grade, even if the issue about the number and locations of the cores is still a matter of debate. Conclusions: At present, SPBx seems to be really necessary in men with persistent suspicion of PCa after negative initial biopsy and probably in patients with a multifocal high-grade prostatic intraepithelial neoplasia or atypical small acinar proliferation. In the remaining situations, adopting an individualized scheme is preferable.

Anaesthesia in Transrectal Prostate Biopsy: Which Is the Most Effective Technique?

Background: Prostate biopsy (PBx) techniques have changed significantly since the original Hodge’s scheme, with an increase in the number and location of cores. These improvements have been realized in part because of the introduction of different local anaesthesia techniques. We critically analysed the literature discussing the role of anaesthesia techniques for use during PBx to find which technique provides the best pain relief for the patient and safety for the urologist. Methods: We performed a literature review by searching the Medline database for articles published between January 2000 and March 2010. Electronic searches were limited to the keywords ‘transrectal prostate biopsy’ and ‘anaesthesia’. Results: Pain and discomfort perceived during PBx are the result of different anatomic factors: the introduction to and movement of the transrectal ultrasound probe in the rectum and the needle piercing the rectum and the prostate capsule. The anaesthesia techniques currently available can be divided into two groups: local (i.e. intrarectal lubricant agents, periprostatic nerve blocks, caudal blocks, pudendal nerve blocks, and their different combinations) and systemic (i.e. oral/intravenous drug administration and sedoanalgesia). Conclusions: The most effective anaesthesia technique for transrectal PBx performed in outpatient settings is the periprostatic nerve blocks with 1 or 2% lidocaine 10 ml, which is associated with intrarectal lubricant agents, especially in younger people. Nevertheless, the current choice of the anaesthesia technique still depends both on patient characteristics (age, prostate size, number and location of cores, anxious personality, need for re-biopsy) and, above all, the urologist’s experience and habits.