Eugenio Brunocilla

Early Biochemical Relapse After Radical Prostatectomy: Which Prostate Cancer Patients May Benefit from a Restaging 11C-Choline PET/CT Scan Before Salvage Radiation Therapy?

The aim of the study was to assess which factors may influence 11C-choline PET/CT detection rate in a population of recurrent prostate cancer (PCa) patients listed for salvage radiation therapy (S-RT) in an early phase of biochemical relapse, to select which patients could obtain the most benefit by performing restaging 11C-choline PET/CT before S-RT. Methods: The study comprised 605 patients, treated with radical prostatectomy (RP) with curative intent for PCa who showed rising PSA levels after primary therapy and listed for S-RT. Prostate-specific antigen (PSA) values were >0.2 ng/mL and <2 ng/mL (mean, 1.05 ng/mL; median, 1.07 ng/mL; range, 0.2–2 ng/m; SD, ±0.59). All patients were classified as N0 after RP. Seventeen of 605 patients received adjuvant RT together with RP, whereas 148 of 605 patients received androgen-deprivation therapy (ADT) at the time of PET/CT. PSA, PSA kinetics, Gleason score, age, time to biochemical relapse, ADT, and initial tumor stage were statistically analyzed to assess which factor could influence PET/CT positivity and the detection of local versus distant relapse. Results: 11C-choline PET/CT was positive in 28.4% of patients (172/605). Eighty-three of 605 patients were positive in the pelvis (group A), distant metastasis (group B) were detected in 72 of 605 patients, and local and distant sites of relapse were detected in 17 of 605 patients (group C). At multivariate analysis, PSA, PSA doubling time (PSAdt), and ongoing ADT were significant predictors for positive scan results, whereas PSA and PSAdt were significantly related to distant relapse detection (P < 0.05). At the receiver-operating-characteristic analysis, a PSA value of 1.05 ng/mL and PSAdt of 5.95 mo were determined to be the optimal cutoff values in the prediction of a positive 11C-choline PET/CT scan, with an area under the curve (AUC) of 0.625 for PSA and 0.677 for PSAdt. Conclusion: 11C-choline PET/CT may be suggested before S-RT during the early phase of biochemical relapse, to select patients who may benefit from this aggressive treatment. Particularly, patients showing fast PSA kinetics or PSA increasing levels despite ongoing ADT should be studied with 11C-choline PET/CT before S-RT, considering the higher probability to detect positive findings outside the pelvis.

18F-FACBC compared with 11C-choline PET/CT in patients with biochemical relapse after radical prostatectomy: a prospective study in 28 patients.

INTRODUCTION The aim of our study was to compare the detection rate of anti-3-18F-FACBC PET/CT in comparison with 11C-choline PET/CT in the evaluation of disease recurrence of PCa after radical prostatectomy. PATIENTS AND METHODS Twenty-eight consecutive patients with biochemical relapse after radical prostatectomy were submitted to anti-3-18F-FACBC PET/CT and 11C-choline PET/CT to evaluate the site of disease recurrence. Androgen deprivation therapy was avoided in all cases. The primary end point was the overall detection rate of the 2 radiotracers. A patient-based analysis and a lesion-based analysis was performed. The target to background ratio (TBR) of each lesion was reported. RESULTS At the time of PET scan, mean age was 67 years and mean prostate specific antigen (PSA) relapse was 2.9 ng/mL (range: 0.2-14.6). In patient-based analyses, 11C-choline PET/CT was positive in 5 patients and negative in 23 (detection rate = 17.8%) and anti-3-18F-FACBC PET/CT was positive in 10 patients and negative in 18 (detection rate = 35.7%). All lesions that were positive using 11C-choline were positive using anti-3-18F-FACBC PET/CT but with the latter radiotracer, 11 (61.1%) additional tumors were identified including 5 (17.8%) additional patients. The TBR of anti-3-18F-FACBC was greater than 11C-choline in 15 of 18 lesions, confirming a better image quality and contrast. CONCLUSION This preliminary study demonstrated that the detection rate of anti-3-18F-FACBC PET/CT is greater in comparison with 11C-choline, with approximately 20% of additional patients and approximately 60% additional lesions detected. Further studies, however, are required to assess the exact added value of this new tracer.

Can Testis-Sparing Surgery for Small Testicular Masses Be Considered a Valid Alternative to Radical Orchiectomy? A Prospective Single-Center Study

BACKGROUND The aim of this study was to evaluate the incidence of malignancy in small testicular masses (STMs) treated with testis-sparing surgery (TSS) with intraoperative frozen section analysis and to assess the safety of this surgical procedure. PATIENTS AND METHODS From January 2009 to January 2013, 15 consecutive patients underwent TSS for STMs in a third-referral academic institution. Every patient was preoperatively evaluated with clinical examination and scrotal ultrasonography (US) performed by the same radiologist. Tumor markers were assessed in all cases. All the procedures were performed through inguinal access; the small mass was identified by straight palpation of the testis or with intraoperative ultrasonography (IUS). Frozen-section examination (FSE) was performed in all patients in association with multiple biopsies of the surrounding tissue. Follow-up was carried out in all patients with an ultrasonographic exploration at 6 and 12 months. RESULTS Preoperative tumor markers were normal in all patients. The mean operative time was 90 ± 31 minutes. The warm ischemia time was 18 ± 3 minutes. The mean size on US was 9.5 ± 4.4 mm. FSE results were confirmed by the final pathologic analysis in 14 patients. At final pathologic analysis, 6 patients (40%) were found not to have tumors, another 7 patients (46.7%) had benign neoplasms, and malignant tumor was found in only 2 patients (13.3%). There was no disease recurrence after a mean follow-up of 19.2 ± 11.5 months. CONCLUSION Our experience shows that TSS performed for STMs may represent a safe procedure with optimal results in terms of functional and oncologic end points.

Small Renal Masses Initially Managed Using Active Surveillance: Results From a Retrospective Study With Long-Term Follow-Up

BACKGROUND The purpose of this study was to provide outcomes of patients managed using active surveillance (AS) for small renal masses (SRMs). PATIENTS AND METHODS We retrospectively reviewed data of 62 patients diagnosed with 64 contrast enhancing SRMs suspicious for renal cell carcinoma. We evaluated the differences between patients who remained on AS and those who underwent delayed surgical intervention. RESULTS The mean age of patients was 75 years and the mean follow-up was 91.5 months. The median tumor size and the median estimated tumor volume were 2.6 cm and 8.7 cm(3), respectively. The median linear growth rate and the median volumetric growth rate were 0.7 cm/y and 8.8 cm(3)/y, respectively. The mean linear and volumetric growth rates of the group of patients who underwent surgery was higher than in those who remained on surveillance (1.9 vs. 0.4 cm/y and 16.1 vs. 4.6 cm(3)/y, respectively; P < .001). CONCLUSION Most SRMs show an indolent course, with low metastatic potential. Faster linear and volumetric growth rates could be the expression of malignant disease, thus suggesting the need for a delayed surgical intervention. AS is a reasonable option for the management of SRMs in properly selected patients with low life expectancy.

Diagnostic Accuracy of 11C-Choline PET/CT in Preoperative Lymph Node Staging of Bladder Cancer: A Systematic Comparison With Contrast-Enhanced CT and Histologic Findings

Aim The aim of this study was to evaluate the role of 11C-choline PET/CT in the preoperative evaluation of the nodal involvement of patients with bladder carcinoma (BC) suitable for radical cystectomy and extended pelvic lymph node dissection in comparison with contrast-enhanced CT (CECT) using the pathologic specimen as reference standard. Patients and Methods Twenty-six consecutive patients (69.5 ± 9.3 years; range, 49–84) with histologically proven transitional cell BC were treated with radical cystectomy and pelvic lymph node dissection and were enrolled from April 2011 to January 2013. In all patients, paravesical, internal, eternal, and common iliac nodes as well as obturatory, presacral, preaortic, and precaval lymph nodes (LNs) were dissected up to the origin of the inferior mesentery artery. The areas of the LN dissection were grouped as follow: region A included preaortic and precaval LNs; region B included paravesical, common, internal and external iliac, obturatory, and presacral LNs in the right pelvis; region C included paravesical, common, internal and external iliac, obturatory, and presacral LNs in the left pelvis. 11C-choline PET/CT and abdominal CECT were used to assess the presence of lymph node metastases on a per patient, region, and lesion analysis using the results of surgical specimens obtained at operation as criterion standard. Results Seven of 26 patients (26.9%) showed nodal metastases at pathologic analysis. Overall, 844 LNs were evaluated, and 38 of them (4.5%) showed metastatic involvement. On a patient-based analysis, 11C-choline PET/CT showed a sensitivity of 42% and specificity of 84%, whereas, CECT showed a sensitivity of 14% and specificity of 89%. On a region-based analysis, 11C-choline PET/CT showed a sensitivity of 11% and specificity of 82%, whereas CECT showed a sensitivity of 5% and specificity of 80%. On a lesion (LN)-based analysis, 11C-choline PET/CT showed a sensitivity of 10% and specificity of 64%, whereas CECT showed a sensitivity of 2% and specificity of 63%. Conclusions 11C-choline PET/CT could provide additional diagnostic information in preoperative nodal staging of patients with invasive BC in comparison with CECT. A study with a larger population should determine if 11C-choline PET/CT could be recommended as a routine technique in high-risk patients with BC.

Positron-emission tomography in imaging and staging prostate cancer

With increasing application of positron-emission tomography (PET) imaging, familiarity with the applications of PET in genitourinary oncology, especially prostate-cancer (PCa) imaging, becomes important. PET studies provide functional information using radiolabeled tracers, with fluoro-dexoxy-glucose (FDG) being the most commonly used. Nevertheless FDG has limitations for evaluation of PCa patients and therefore alternative tracers are being investigated. To date, the best results have been obtained with 11C-choline and 11C-acetate PET, which seem to demonstrate similar values in this field. We review the current role of PET in PCa patients based on data published in the literature as well as our own experience. Most studies of PET imaging of PCa address three goals: a) detecting primary PCa; b) staging PCa; and c) assessing PCa recurrence. From available results, routine clinical use of 11C-choline PET cannot be recommended for detecting and staging primary PCa. At present, the only clinical indication for imaging PCa with 11C-choline-PET is evaluation of suspected recurrence after treatment.

Differing risk of cancer death among patients with lymph node metastasis after radical prostatectomy and pelvic lymph node dissection: identification of risk categories according to number of positive nodes and Gleason score

Lymph node (LN) status is one of the most important prognostic variables in patients undergoing radical prostatectomy, but not all patients with node‐positive PCa are at the same risk of recurrence and cancer‐specific death. In this study we evaluated the role of pathological variables in stratifying the risk of cancer death in patients with prostate cancer. Patients with 1–3 positive LNs and Gleason score (GS) ≤7 experienced better CSS and OS than those with >3 metastatic LNs and/or GS >7. This evidence could allow urologists to better predict oncological outcomes of patients and select more appropriate therapeutic management.

PADUA and R.E.N.A.L. nephrometry scores correlate with perioperative outcomes of robot-assisted partial nephrectomy: analysis of the Vattikuti Global Quality Initiative in Robotic Urologic Surgery (GQI-RUS) database.

To evaluate and compare the correlations between Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) and R.E.N.A.L. [Radius (tumour size as maximal diameter), Exophytic/endophytic properties of the tumour, Nearness of tumour deepest portion to the collecting system or sinus, Anterior (a)/posterior (p) descriptor and the Location relative to the polar line] nephrometry scores and perioperative outcomes and postoperative complications in a multicentre, international series of patients undergoing robot‐assisted partial nephrectomy (RAPN) for masses suspicious for renal cell carcinoma (RCC).

Neutrophil Gelatinase-Associated Lipocalin Increases HLA-G+/FoxP3+ T-Regulatory Cell Population in an In Vitro Model of PBMC

Background Neutrophil gelatinase-associated lipocalin (NGAL) is emerging as a mediator of various biological and pathological states. However, the specific biological role of this molecule remains unclear, as it serves as a biomarker for many conditions. The high sensitivity of NGAL as a biomarker coupled with relatively low specificity may hide important biological roles. Data point toward an acute compensatory, protective role for NGAL in response to adverse cellular stresses, including inflammatory and oxidative stress. The aim of this study was to understand whether NGAL modulates the T-cell response through regulation of the human leukocyte antigen G (HLA-G) complex, which is a mediator of tolerance. Methodology/Principal Findings Peripheral blood mononuclear cells (PBMCs) were obtained from eight healthy donors and isolated by centrifugation on a Ficoll gradient. All donors gave informed consent. PBMCs were treated with four different concentrations of NGAL (40–320 ng/ml) in an iron-loaded or iron-free form. Changes in cell phenotype were analyzed by flow cytometry. NGAL stimulated expression of HLA-G on CD4+ T cells in a dose- and iron-dependent manner. Iron deficiency prevented NGAL-mediated effects, such that HLA-G expression was unaltered. Furthermore, NGAL treatment affected stimulation of regulatory T cells and in vitro expansion of CD4+ CD25+ FoxP3+ cells. An NGAL neutralizing antibody limited HLA-G expression and significantly decreased the percentage of CD4+ CD25+ FoxP3+ cells. Conclusions/Significance We provide in vitro evidence that NGAL is involved in cellular immunity. The potential role of NGAL as an immunomodulatory molecule is based on its ability to induce immune tolerance by upregulating HLA-G expression and expansion of T-regulatory cells in healthy donors. Future studies should further evaluate the role of NGAL in immunology and immunomodulation and its possible relationship to immunosuppressive therapy efficacy, tolerance induction in transplant patients, and other immunological disorders.

Differing Risk of Cancer Death Among Patients With Pathologic T3a Renal Cell Carcinoma: Identification of Risk Categories According to Fat Infiltration and Renal Vein Thrombosis

OBJECTIVES The study objectives were to evaluate the prognostic impact of fat infiltration and renal vein thrombosis in patients with pT3a renal cell carcinoma (RCC) and to identify new prognostic groups. MATERIAL AND METHODS We analyzed 122 consecutive patients with pT3a who underwent radical nephrectomy for RCC between 2000 and 2011 at the University of Bologna. Cancer-specific survival (CSS) rates were estimated using Kaplan-Meier survival curves; univariable and multivariable analyses were performed with Cox analysis. RESULTS The mean follow-up was 41.7 ± 35.4 months. Patients with peritumoral/hilar fat infiltration (n = 63) and patients with renal vein thrombosis (n = 18) experienced comparable CSS rates, whereas patients with both fat infiltration plus renal vein thrombosis (n = 41) showed worse survival outcomes than the first group (P = .026). Patients were divided in 2 groups: group A, with fat invasion or renal vein thrombosis, and group B, with concomitant fat invasion and renal vein invasion. Group B showed worse cancer-specific survival than group A (P = .024). At multivariate analysis, this new risk-group stratification was found to be an independent prognostic predictor of CSS (P < .05). CONCLUSIONS Patients with T3a RCC with both fat invasion and renal vein thrombosis experience worse survival rates when compared with those patients with only 1 prognostic factor. The TNM classification should consider the concomitant presence of those parameters as a different prognostic predictor.