Andrea B. Galosi

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.

Molecular pathology of non-invasive urothelial carcinomas (part I)

An international consultation on the diagnosis of non-invasive urothelial neoplasms was held in Ancona, Italy in May 2001. Besides histology and problems of classification, one group of experts (Committee no. 3) discussed the molecular pathology and cytometry of non-invasive urothelial carcinomas. In the following first part, special immunohistochemical and molecular markers for stratifications in bladder cancer were discussed including different cytokeratins (clone 34βE12, CK 20), cell proliferation markers (Ki67/MIB-1, PCNA, AgNOR, DNA-cytometry), tumor suppressor genes and oncogenes (p53, p21, erb-B2, bcl-2), different receptor expressions of epidermal growth factor and vascular endothelial growth factor and others. These molecular markers were analyzed in diagnosis of urothelial carcinomas, recurrences, progression and response to treatment.

Pressure-Flow Studies in Men with Benign Prostatic Hypertrophy before and after Treatment with Transurethral Needle Ablation

Background/Aims: In this study we wanted to examine the effects that transurethral needle ablation (TUNA) might have on the urodynamic characteristics of bladder outlet obstruction and to evaluate the clinical changes and the safety profile in patients undergoing the TUNA procedure, including the effects on erectile and ejaculatory function. Materials and Methods: We evaluated 24 patients, aged between 66 and 81 (mean 73.4) years with a mean prostatic volume of 57 ± 15 ml. Before treatment, the clinical history was collected, then prostate-specific antigen (PSA) analysis, digital rectal examinations, I-PSS and quality-of-life (QOL) tests, uroflowmetry with residual volume, and pressure-flow studies were performed in all patients. After treatment, all the patients were evaluated at 6, 12 and 24 months by the same parameters. Results: After treatment, the I-PSS and QOL scores were considerably improved, and the mean flow rate and the residual volume were also improved. The serum PSA level remained unchanged. The prostatic volume was almost unchanged, and pressure-flow studies showed a reduction in the mean opening pressure and detrusor pressure at maximum flow after treatment. None of the patients complained of alterations in sexual activity nor retrograde ejaculation. Conclusions: Our study confirms that in patients with benign prostatic hyperplasia, the TUNA procedure results in no major complications and in significant clinical improvements. There was an improvement in the subjective and objective variables, such as symptom scores and frequency-volume charts and, in the majority of patients, subjective and objective improvements were sustained for the duration of this study, which included a 2-year follow-up with pressure-flow studies. From our experience we can say that the ideal candidate for TUNA treatment should be younger than 70 years, with a prostatic volume of <60 cm H2O, with a baseline detrusor pressure at maximum flow of <60 cm H2O, with a pretreatment residual volume of <100 ml and with a QOL score of <5.

Bicalutamide 50 mg monotherapy in patients with isolated high‐grade PIN: findings in repeat biopsies at 6 months

Objectives: To evaluate morphological findings in repeat biopsies in patients with isolated high-grade prostatic intraepithelial neoplasia (HGPIN) after a 6-month course of bicalutamide (Casodex) 50 mg/day. Methods: 20 consecutive patients with isolated HGPIN in prostate biopsies were treated for 6 months with bicalutamide 50 mg/day. After treatment, the patients were resubmitted to prostate biopsy mapping. The control group included 22 untreated consecutive patients with isolated high-grade PIN with repeat biopsies taken 6 months after the initial biopsies. Results: In the initial biopsies of the treated group, HGPIN was monofocal in 12 patients and plurifocal in 8. In the repeat biopsies HGPIN was present in 2 patients, monofocal in both, whereas prostate adenocarcinoma (PCa) was discovered in one. In the control group, HGPIN was monofocal in 15 and plurifocal in 7. In the repeat biopsies HGPIN was present in six patients, being monofocal in three and plurifocal in the other three. PCa was present in one. Conclusions: There was a lower incidence of HGPIN (treated group vs control: 10% vs 27.2%) after 6 months of bicalutamide. Reduction in its extent was also observed (treated group vs control: monofocal 100% vs 50%). Treatment did not affect the incidence of cancer (treated vs control: 5% vs 4.5%).

Diagnostic Accuracy of Percent Free Prostate-Specific Antigen in Prostatic Pathology and Its Usefulness in Monitoring Prostatic Cancer Patients

Introduction: The aim of our study was to evaluate the clinical usefulness of percent free prostate-specific antigen (PSA) [ratio of free PSA (fPSA) to total PSA (tPSA); f/tPSA] in prostatic pathology and its usefulness in monitoring prostatic cancer patients. Patients and Methods: Our prospective study was carried out on 470 consecutive male patients referred to our outpatient urological clinic for observation. We looked for relationships between tPSA, fPSA and percent free PSA and the patient’s age, prostatic volume and histologic diagnosis as assessed by prostatic biopsies or surgical specimens (benign prostatic hypertrophy, carcinoma, hypertrophy with inflammation). In all cases, we calculated the specificity, sensitivity and diagnostic accuracy of percent free PSA in the diagnosis of prostatic diseases, using cutoff values ranging from 14 to 20%. In prostatic cancer patients, we considered the relationships between the various PSA molecular forms and staging, grading and follow-up values. We also evaluated the effects of hormonosuppressive therapy on the serum markers and noted for which tPSA value percent free PSA possessed the greatest diagnostic accuracy. Results: While tPSA and fPSA values appeared to be correlated with patient age and prostatic volume, percent free PSA did not show a relationship with these parameters. The specificity, sensitivity and overall diagnostic accuracy were better assuming a 16% cutoff value for percent free PSA than with other cutoff values. Prostatic inflammation associated with benign hypertrophy can cause false positives in both tPSA and f/tPSA measurements, since 60% of these patients have an f/tPSA ratio below 16%. In diagnosing carcinoma, the diagnostic accuracy of percent free PSA is 100% when tPSA is between 2.5 and 4.0 ng/ml. Percent free PSA is not linked with staging in prostatic cancer, but it does appear to be related to the Gleason score. In patients receiving hormonosuppressive treatment, f/tPSA decreased significantly, and more so in patients with a higher Gleason score. In patients with disease in rapid progression, percent free PSA was lower than in patients in a stable condition. Conclusions: Based on our experience, 16% as the f/tPSA cutoff value for discriminating between benign and malignant pathologies is the best possible choice, as it provides the highest overall values of sensitivity, specificity and diagnostic accuracy (80, 61.5 and 84.5%, respectively) in the diagnosis of prostatic cancer. We believe that f/tPSA is not a definitive test for diagnosing prostatic cancer. Our observations on the behavior of percent free PSA in relation to prostatic carcinoma grading and staging and in the follow-up of carcinoma patients are interesting; however, further studies are needed to define the appropriate role of f/tPSA in patients with an established diagnosis of prostatic carcinoma and in the follow-up of patients with prostatic cancer.

Diagnosis of isolated high-grade prostatic intra-epithelial neoplasia: proposal of a nomogram for the prediction of cancer detection at saturation re-biopsy

Study Type – Diagnostic (case series)

Update on histopathological evaluation of lymphadenectomy specimens from prostate cancer patients.

BackgroundMetastases to lymph nodes (LNs) represent an unfavorable prognostic factor in patients with prostate cancer (PCa). Histological examination represents the gold standard in the evaluation of the lymphadenectomy (LND) specimens for the presence of secondary deposits.Methods and resultsThe metastatic detection rate can vary according to the approach adopted in the microscopic analysis of the LNs, which includes frozen-section examination, total inclusion of the tissue with and without whole-mount sections, serial sectioning, and the application of immunohistochemistry. The assessment of the sentinel LN, the search for micrometastases, and the evaluation of atypical LN metastatic sites further contribute to the detection of the metastatic spread.ConclusionIn this review, an update on the histopathological evaluation of LND specimens in patients with PCa is given, and focus is made on their clinical and prognostic significance.

Solitary Fibrous Tumour of the Prostate Identified on Needle Biopsy

The clinical and radical prostatectomy features of a case of solitary fibrous tumour (SFT) of the prostate identified on needle biopsy are presented. The main differential diagnoses are discussed. SFTs involving the prostate are relatively uncommon, with only isolated cases reported in the literature. Owing to their relative rarity and lack of long-term follow-up, the clinical behaviour of prostatic SFTs is difficult to predict. Complete resection of the tumour is currently the single main prognostic factor.

Immunohistochemical Detection and Localization of Somatostatin Receptor Subtypes in Prostate Tissue from Patients with Bladder Outlet Obstruction

Background and Aim of the Study: Scant information on the cellular distribution of the five somatostatin receptor (SSTR) subtypes in the normal prostate and in neoplasms of the prostate has been reported in very few studies in which techniques, such as in situ hybridization histochemistry, autoradiography, and more recently immunohistochemistry, have been applied. The aim of the study was to examine immunohistochemically the distribution and localization of these 5 subtypes in the various tissue components in normal prostate. Materials: The study was conducted in 14 surgical specimens of normal prostate tissue from adenomectomy specimens from patients with bladder outlet obstruction. The distribution and localization of the 5 somatostatin receptor (SSTR) subtypes was investigated with an immunohistochemical technique. Specificity of the antibodies against the 5 receptor subtypes was preliminarily investigated. Results: Close to 90% of secretory cells showed a weak positivity in the cytoplasm, the proportion ranging from 86.3% (SSTR4) to 89.9% (SSTR5). Strong immunoreactivity was seen in a small proportion of cells, ranging from 0.8% (SSTR3) to 3.2% (SSTR1). For the subtypes 1 and 3 the greatest proportion of basal cells showed a moderate intensity (42.5 and 41.4%, respectively), strong immunoreactivity being observed only in 18.1 and 15.8% of cells, respectively. For the subtypes 2, 4 and 5, the majority of cells showed a weak intensity (72.3, 65.7 and 65.1%, respectively). Subtype 1 showed a strong immunoreactivity in the cytoplasm in 60% of the smooth muscle cells. With subtypes 2, 3 and 4 the greatest proportion of cells showed a weak intensity (63.4, 89.8 and 81.7%, respectively). With the subtype 5 the majority of cells (59.8%) were negative. Subtype 1 showed a strong immunoreactivity in the cytoplasm in 98.6% of the endothelial cells. With subtypes 3 and 4 the greatest proportion of cells showed a weak intensity (73.5 and 56.4%, respectively). With the subtype 2 and 5 the majority of cells were negative (59.1 and 50.7%, respectively). Conclusions: Our immunohistochemical study on the SSTRs expands our knowledge in the distribution of these subtypes in the various tissue components in the prostate. Such an information may prove useful in developing further non-surgical strategies for the prevention and treatment of benign prostatic hyperplasia and, in particular, of preneoplastic and neoplastic lesions of the prostate.

Seminal Vesicle Intraepithelial Neoplasia Versus Basal Cell Hyperplasia in a Seminal Vesicle

In the examination of >3000 radical prostatectomy specimens and their seminal vesicles (SVs), we came across a unique case of an intraepithelial abnormality in preexisting ducts and acini in the left SV of a 73-yr-old patient with prostatic adenocarcinoma. At low magnification, the epithelial lining was thicker than the surrounding normal ducts with obliteration of the acinar lumen. At high magnification, there were varying degrees of cell stratification. Prostate-specific antigen, prostate-specific acid phosphatase, prostate-specific membrane antigen, prostein (P501S), alpha-methylacyl-CoA racemase, and GATA binding protein 3 (GATA3) were negative; p63, 34betaE12, cytokeratin 5/6, and p53 were positive in cells in basal and suprabasal positions, whereas CA-125 was expressed in the luminal cells. The case shows morphologic and immunohistochemical features similar to those of basal cell hyperplasia of the prostate and is different from the early neoplastic epithelial changes of the SV in the transgenic adenocarcinoma mouse prostate model (ie, SV intraepithelial neoplasia). To the best of our knowledge, there are no previous reports of such a change in a human SV. The clinical significance of this lesion is not known and is overshadowed by the presence of prostate cancer.