Riccardo Schiavina

11C-Choline Positron Emission Tomography/Computerized Tomography for Preoperative Lymph-Node Staging in Intermediate-Risk and High-Risk Prostate Cancer: Comparison with Clinical Staging Nomograms

BACKGROUND Conventional imaging (CI) techniques are inadequate for lymph node (LN) staging in prostate cancer (PCa). OBJECTIVES To assess the accuracy of (11)C-Choline positron emission tomography/computerized tomography (PET/CT) for LN staging in intermediate-risk and high-risk PCa and to compare it with two currently used nomograms. DESIGN, SETTING, AND PARTICIPANTS From January 2007 to September 2007, 57 PCa patients at intermediate risk (n=27) or high risk (n=30) were enrolled at two academic centres. All patients underwent preoperative PET/CT and radical prostatectomy with extended pelvic LN dissection (PLND). Risk of LN metastasis (LNM) was assessed using available nomograms. MEASUREMENTS Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and number of correctly recognized cases for LNM detection at PET/CT were assessed. The accuracy of PET/CT for LNM detection was compared with the accuracy of nomograms for LNM prediction by using receiver operating characteristic (ROC) analysis. RESULTS AND LIMITATIONS Fifteen patients (26%) had LNMs, and a total of 41 LNMs were identified. On a patient analysis, sensitivity, specificity, PPV, NPV, and number of correctly recognized cases at PET/CT were 60.0%, 97.6%, 90.0%, 87.2%, and 87.7% while, on node analysis, these numbers were 41.4%, 99.8%, 94.4%, 97.2%, and 97.1%. The mean diameter (in mm) of the metastatic deposit of true-positive LNs was significantly higher than that of false-negative LNs (9.2 vs 4.2; p=0.001). PET/CT showed higher specificity and accuracy than the nomograms; however, in pairwise comparison, the areas under the curve (AUCs) were not statistically different (all p values >0.05). CONCLUSIONS In patients with intermediate-risk and high-risk PCa, (11)C-Choline PET/CT has quite a low sensitivity for LNM detection but performed better than clinical nomograms, with equal sensitivity and better specificity.

Simple Enucleation is Equivalent to Traditional Partial Nephrectomy for Renal Cell Carcinoma: Results of a Nonrandomized, Retrospective, Comparative Study

PURPOSE The excision of the renal tumor with a substantial margin of healthy parenchyma is considered the gold standard technique for partial nephrectomy. However, simple enucleation showed excellent results in some retrospective series. We compared the oncologic outcomes after standard partial nephrectomy and simple enucleation. MATERIALS AND METHODS We retrospectively analyzed 982 patients who underwent standard partial nephrectomy and 537 who had simple enucleation for localized renal cell carcinoma at 16 academic centers between 1997 and 2007. Local recurrence, cancer specific survival and progression-free survival were the main outcomes of this study. The Kaplan-Meier method was used to calculate survival functions and differences were assessed with the log rank statistic. Univariable and multivariable Cox regression models addressed progression-free survival and cancer specific survival. RESULTS Median followup of the patients undergoing traditional partial nephrectomy and simple enucleation was 51 ± 37.8 and 54.4 ± 36 months, respectively (p = 0.08). The 5 and 10-year progression-free survival estimates were 88.9 and 82% after standard partial nephrectomy, and 91.4% and 90.8% after simple enucleation (p = 0.09). The 5 and 10-year cancer specific survival estimates were 93.9% and 91.6% after standard partial nephrectomy, and 94.3% and 93.2% after simple enucleation (p = 0.94). On multivariable analysis the adopted nephron sparing surgery technique was not an independent predictor of progression-free survival (HR 0.8, p = 0.55) and cancer specific survival (HR 0.7, p = 0.53) when adjusted for the effect of the other covariates. CONCLUSIONS To our knowledge this is the first multicenter, comparative study showing oncologic equivalence of standard partial nephrectomy and simple enucleation.

Role of 11C-choline PET/CT in the re-staging of prostate cancer patients with biochemical relapse and negative results at bone scintigraphy

AIM to evaluate the utility of (11)C-choline PET/CT in prostate cancer (PC) patients who have demonstrated a biochemical recurrence and a negative bone scintigraphy (BS). MATERIALS AND METHODS 123 consecutive PC patients (mean age 67.6 years; range 54-83) with a biochemical relapse (mean PSA value 3.3ng/mL; range 0.2-25.5) after radical prostatectomy (RP) were included in our retrospective study. Patients underwent a BS that resulted negative and a (11)C-choline PET/CT within 4 months from BS (range: 1 day to 4 months; mean: 2.5 months). Validation of results was established by: (1) a positive biopsy, (2) a positive subsequent BS, CT or MR and (3) a normalization of (11)C-choline uptake after systemic therapy or a progression of the disease. RESULTS (11)C-choline PET/CT was positive in 42/123 patients (34.1%). (11)C-choline PET/CT detected lesions in: bone (10 patients), lymph-nodes (20 patients), bone and lymph nodes (7 patients), bone and lung (1 patient), lymph-nodes and lung (1 patient), local relapse (3 patients). Overall, (11)C-choline PET/CT showed a total of 30 unknown bone lesions in 18/123 (14.6%) patients. CONCLUSION (11)C-choline PET/CT showed a better sensitivity than BS in patients with biochemical relapse after RP: (11)C-choline PET/CT detected unknown bone lesions in 18/123 (14.6%) patients.

Diagnostic role of circulating free plasma DNA detection in patients with localized prostate cancer

To analyze the potential diagnostic relevance of free plasma DNA (FPDNA), we enrolled 64 patients with localized prostate cancer (CaP). FPDNA was quantified by real-time polymerase chain reaction assessment of the HTERT gene in blood samples from 64 patients with CaP and 45 healthy males. Methylation of the GSTP1 gene was used to confirm the neoplastic origin of FPDNA in selected cases. The mean +/- SD levels of FPDNA were higher in patients with CaP (15.4 +/- 10.9 ng/mL) than in control subjects (5.5 +/- 3.5 ng/mL; P <.001). By using the best cutoff value, the sensitivity of the test was 80%, the specificity was 82%, the area under the receiver operating characteristic curve, 0.881. High FPDNA values were significantly associated with pathologic T3 stage (P = . 035). Methylation of the GSTP1 gene was found in 4 (25%) of 16 FPDNA samples and 15 (94%) of 16 tissue samples. Quantification of FPDNA discriminates between patients with CaP and healthy subjects and correlates with pathologic tumor stage. FPDNA is a candidate biomarker for early diagnosis and monitoring of CaP.

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.

The role of 11C-choline PET imaging in the early detection of recurrence in surgically treated prostate cancer patients with very low PSA level <0.5 ng/mL.

Purpose This study aims to evaluate the role of 11C-choline PET/CT in patients with biochemical relapse after radical prostatectomy (RP) showing prostate-specific antigen (PSA) values lower than 0.5 ng/mL. Methods We performed 11C-choline PET/CT in 71 consecutive patients previously treated with RP showing PSA values lower than 0.5 ng/mL. 11C-Choline PET/CT was performed following standard procedure. 11C-Choline PET/CT–positive findings were validated by transrectal ultrasonography + biopsy, repeated 11C-choline PET/CT, other conventional imaging modality, and histology. Results 11C-Choline PET/CT was true positive in 15/71 (21.1%). 11C-Choline uptake was observed in pelvic lymph nodes (7/71; 9.9%), in the prostatic bed (7/71; 9.9%), and in bone (1/71; 1.4%). Mean PSA, PSA doubling time (PSAdt), and PSA velocity (PSAvel) values ± SD in 11C-choline PET/CT–positive patients was 0.37 ± 0.1 ng/mL, 3.4 ± 2.1 months, and 0.05 ± 0.1 ng/mL/yr, respectively. 11C-Choline PET/CT was false negative in 2 patients and false positive in 1 patient. Among all variables, only PSAdt and the ongoing hormonal treatment were statistically significant in the prediction of a positive 11C-choline PET/CT at multivariate analysis. Conclusions 11C-Choline PET/CT could be used early after biochemical failure even if PSA values are very low, preferentially in hormonal resistant patients showing fast PSA kinetics. An early detection of the site of relapse could lead to a personalized and tailored treatment.

Positive Surgical Margins After Nephron-Sparing Surgery for Renal Cell Carcinoma: Incidence, Clinical Impact, and Management

Nephron-sparing surgery (NSS) for renal cell carcinoma (RCC) offers comparable oncologic results but a lower risk of chronic kidney disease when compared with radical nephrectomy; however it can result in positive surgical margins (PSMs) and consequently to a possible risk of oncologic failure. The aim of this review is to evaluate the incidence of PSMs after nephron-sparing surgery, to assess their clinical and oncologic impact, and to provide an overview of the possible therapeutic management. We performed a nonsystematic review of the literature in the MEDLINE database using the following keywords: partial nephrectomy, nephron-sparing surgery, and positive margin. We reviewed articles published only in English from January 2002 to May 2012. The overall incidence of PSMs after NSS ranges from 0% to 7%, with no significant differences in open, laparoscopic, and robot-assisted techniques. Smaller tumor size could result in a higher risk of PSMs. Even if there is not a clear agreement in the clinical evidence, local recurrence seems to be more likely in patients with PSMs, especially in those with high-grade tumors. Development of metastases and cancer-specific survival, as seen in midterm follow-up studies, seems to be comparable to those in patients with negative surgical margins. Considering the globally low risk of local recurrence, development of metastasis, or cancer-specific mortality, careful surveillance could be the best management option for most patients with PSMs after NSS.

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.

The extent of pelvic lymph node dissection correlates with the biochemical recurrence rate in patients with intermediate- and high-risk prostate cancer

Study Type – Therapy (case series)

Simple enucleation versus standard partial nephrectomy for clinical T1 renal masses: Perioperative outcomes based on a matched-pair comparison of 396 patients (RECORd project)

OBJECTIVES To compare simple enucleation (SE) and standard partial nephrectomy (SPN) in terms of surgical results in a multicenter dataset (RECORd Project). MATERIALS AND METHODS patients treated with nephron sparing surgery (NSS) for clinical T1 renal tumors between January 2009 and January 2011 were evaluated. Overall, 198 patients who underwent SE were retrospectively matched to 198 patients who underwent SPN. The SPN and SE groups were compared regarding intraoperative, early post-operative and pathologic outcome variables. Multivariable analysis was applied to analyze predictors of positive surgical margin (PSM) status. RESULTS SE was associated with similar WIT (18 vs 17.8 min), lower intraoperative blood loss (177 vs 221 cc, p = 0.02) and shorter operative time (121 vs 147 min; p < 0.0001). Surgical approach (laparoscopic vs. open), tumor size and type of indication (elective/relative vs absolute) were associated with WIT >20 min. The incidence of PSM was significantly lower in patients treated with SE (1.4% vs 6.9%; p = 0.02). At multivariable analysis, PSM was related to the surgical technique, with a 4.7-fold increased risk of PSM for SPN compared to SE. The incidence of overall, medical and surgical complications was similar between SE and SPN. CONCLUSIONS Type of NSS technique (SE vs SPN) adopted has a negligible impact on WIT and postoperative morbidity but SE seems protective against PSM occurrence.