A. Lapini

Simple Enucleation for the Treatment of Renal Cell Carcinoma Between 4 and 7 cm in Greatest Dimension: Progression and Long-Term Survival

PURPOSE We present our findings in a series of patients treated with simple enucleation for RCC 4 to 7 cm in greatest dimension. We specifically report the incidence of local and systemic recurrence, and the disease specific survival rate. MATERIALS AND METHODS We retrospectively reviewed clinical and pathological data on 71 patients who underwent nephron sparing surgery by simple enucleation between 1986 and 2004 for sporadic, unilateral, pathologically confirmed, 4 to 7 cm RCC. Patients with a solitary kidney due to previous RCC treated with radical nephrectomy were excluded from study. None of the patients had preoperative or intraoperative suspicion of positive nodes. All patients were free of distant metastases before surgery (M0). Patient status was last evaluated in May 2005. Mean followup was 74 months (median 51, range 12 to 225). RESULTS Pathological review according to the 2002 TNM classification showed that 42% of the tumors (30 of 71) were pT1a, 44% (31 of 71) were pT1b and 14% (10 of 71) were pT3a. Mean tumor greatest dimension +/- SD was 4.7 +/- 0.81 cm (median 4.5, range 4.0 to 7.0) cm. None of the patients died within the first 30 days of surgery. There were no major complications requiring open reoperation, such as bleeding and urinary leakage/urinoma. Five and 8-year cancer specific survival was 85.1% and 81.6%, respectively. Five-year cancer specific survival in patients with pT1a (4 cm), pT1b and pT3a disease was 95.7%, 83.3% and 58.3%, respectively (pT1a vs pT1b p = 0.254, pT1a vs pT3a p = 0.006 and pT1b vs pT3a p = 0.143). Overall 10 patients experienced progressive disease (14.9%), of whom 3 had local recurrence (4.5%) alone or local recurrence associated with distant metastases. CONCLUSIONS Simple tumor enucleation is a useful and acceptable approach to nephron sparing surgery for 4 to 7 cm RCC. It provides long-term cancer specific survival rates similar to those of radical nephrectomy and is not associated with a greater risk of local recurrence than partial nephrectomy for RCC less than 4 cm in greatest dimension.

Histopathologic Analysis of Peritumoral Pseudocapsule and Surgical Margin Status after Tumor Enucleation for Renal Cell Carcinoma

BACKGROUND The oncologic safety of blunt tumor enucleation (TE) of renal cell carcinoma (RCC) depends on the presence of a continuous pseudocapsule (PS) around the tumor and on the possibility of obtaining negative surgical margins (SMs). OBJECTIVE To investigate the PS and SMs after TE to define the real need to take a rim of healthy parenchyma around the tumor to avoid the risk of positive SMs. The risk of PS invasion related to other clinical and pathologic variables was also evaluated. DESIGN, SETTING, AND PARTICIPANTS Between September 2006 and December 2007, data were gathered prospectively from 187 consecutive patients who had kidney surgery. Overall, 90 consecutive patients who had TE for RCC were eligible for the study. All specimens were evaluated using an image analyzer by a dedicated uropathologist. INTERVENTION TE was done by blunt dissection using the natural cleavage plane between the tumor and the normal parenchyma. MEASUREMENTS PS, SM, and routinely available clinical and pathologic variables were recorded. RESULTS AND LIMITATIONS In 60 RCC tumors (67%) the PS was intact and free from invasion (PS-) while in 30 (33%) there were signs of penetration within its layers, with or without invasion beyond it. Indeed, 26.6% had PS that had been penetrated on the parenchymal side and 6.6% had penetration on the perirenal fat tissue side. The odds of having PS penetration increased significantly with an increase in clinical tumor size. PS penetration was also significantly associated with pathologic tumor dimensions and grade. In all cases the SMs were negative after TE. The present patients, followed for >2 yr, will enable us to correlate the risk of local recurrence with PS status. CONCLUSIONS The risk of PS penetration is associated with clinical and pathologic tumor dimensions and grade. If there is PS invasion into normal parenchyma, the presence of a thin layer of tissue allows for negative SM even if a TE is performed.

Local staging of prostate carcinoma with endorectal coil MRI: correlation with whole-mount radical prostatectomy specimens

The purpose of this study was to investigate the accuracy of endorectal coil MRI in the local staging of prostate carcinoma. A total of 73 patients with biopsy-proven prostate carcinoma were examined at 0.5 T prior being submitted to radical prostatectomy. The gold standard was provided in all patients by findings at whole-mount sectioning of the surgical specimens. At pathology 28 patients had stage T2, 30 had stage T3a/b, and 15 had stage T3c lesions. Overall accuracy of endorectal coil MRI in defining local tumor stage was 82% (60 of 73 patients). Of 73 patients, 5 (7%) were underestimated and 8 (11%) overestimated. The sensitivity and the specificity of endorectal coil MRI in diagnosing capsular penetration were 95% and 82%, respectively. Seminal vesicle invasion was detected with 80% sensitivity and 93% specificity. Our data indicate that endorectal coil MRI is an accurate method for local staging of prostate cancer.

Conservative Surgical Treatment of Renal Cell Carcinoma: Clinical Experience and Reappraisal of Indications

During a 14-year period 36 patients who presented with renal cell carcinoma underwent conservative surgical treatment. The patients were divided into 3 groups according to treatment indications and condition of the contralateral kidney: group 1 included patients with a solitary kidney or bilateral tumors, group 2 patients had a damaged contralateral kidney and group 3 patients were without abnormalities of the contralateral kidney. Cumulative 6-year survival rates were 58 per cent for group 1, and 90 per cent for groups 2 and 3 combined. The over-all cumulative 6-year survival rate was 74 per cent. Based on these data extension of the indication for conservative surgical treatment seems to be justified in patients who present with low stage tumors and partial or potential damage to the contralateral organ.

Frequency of regulatory T cells in peripheral blood and in tumour-infiltrating lymphocytes correlates with poor prognosis in renal cell carcinoma

What’s known on the subject? and What does the study add?

A Randomized, Placebo-Controlled Study to Assess Safety and Efficacy of Vardenafil 10 mg and Tamsulosin 0.4 mg vs. Tamsulosin 0.4 mg Alone in the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia

INTRODUCTION Safety and efficacy of tamsulosin and vardenafil are well established: however, there is no report regarding combined therapy with these drugs for lower urinary tract symptoms (LUTSs) secondary to benign prostatic hyperplasia (BPH). AIM To compare the safety and efficacy of tamsulosin 0.4 mg/day vs. tamsulosin 0.4 mg/day plus vardenafil 10 mg/day in patients with LUTS/BPH in a randomized trial with 12-week follow-up. METHODS We conducted a randomized, double-blind, placebo-controlled study on 60 men with persistent storage LUTS after 2-week run-in with tamsulosin. MAIN OUTCOME MEASURES International Prostate Symptom Score (IPSS), IPSS-bother, International Index of Erectile Function, Version 5 (IIEF-5) and Over Active Bladder questionnaire (OAB-q) scores, uroflowmetry data (Qmax, Qave), and postvoiding residual urine were recorded after run-in (baseline), and 2 and 12 weeks after treatment. Differences between vardenafil and placebo at different times were calculated with unpaired samples t-test. Between-group differences in change from baseline to 2 and 12 weeks were evaluated with analysis of variance. RESULTS We found a between-group significant difference from baseline to 12 weeks in the following: (i) Qmax (placebo: +0.07, vardenafil: +2.56, P = 0.034); (ii) Qave (placebo: -0.15, vardenafil: +1.02, P = 0.031); (iii) irritative-IPSS subscores (placebo: -1.67, vardenafil: -3.11, P = 0.039); and (iv) IIEF (placebo: +0.06, vardenafil: +2.61, P = 0.030). No patient reported any serious (grade ≥ 2) adverse event (AE). There were no differences in the incidence of common, treatment-related AEs between men undergoing combined therapy or tamsulosin alone. CONCLUSIONS The combination of tamsulosin and vardenafil for 12 weeks was well tolerated and more effective to improve both LUTS and erectile function, as compared with tamsulosin alone. Further studies are needed to assess the role of combined therapy of phosphodiesterase type 5 inhibitors and alpha blockers in treating LUTS/BPH.

The impact of sunitinib-induced hypothyroidism on progression-free survival of metastatic renal cancer patients: a prospective single-center study.

BACKGROUND Several studies have reported unexpected rates of hypothyroidism in patients treated with sunitinib. The biochemical basis of this impairment is unknown. A relationship between hypothyroidism and improved outcome has been suggested in some cancer patients. Here we describe the incidence of newly onset hypothyroidism and its relationship with progression-free survival in metastatic renal cell carcinoma patients undergoing sunitinib treatment at our institution. PATIENTS AND METHODS Between July 2007 and June 2009, 22 patients received a first line sunitinib for metastatic renal cell carcinoma. Thyroid function tests were prospectively evaluated as routine laboratory assessment in every patient, at baseline and on the first and last day of every ON and OFF sunitinib period. RESULTS The median duration of treatment was 39.5 weeks. During sunitinib therapy, 13 patients (59.1%) showed at least one elevated TSH level. No reductions of TSH below normal ranges were observed. L-thyroxine replacement therapy was required in 2 patients. Based on thyroid function, median progression-free survival was 8.55 months for hypothyroid compared with 7.03 months for euthyroid patients (P < 0.05). CONCLUSION Patients administered sunitinib have an high incidence of hypothyroidism. The improved outcome of hypothyroid patients suggests an important relationship between sunitinib and this uncommon side effect.

Pathological characteristics and prognostic effect of peritumoral capsule penetration in renal cell carcinoma after tumor enucleation

OBJECTIVE To evaluate the pathological characteristics of peritumoral capsule (PC) and the prognostic effect of capsule penetration on tumor recurrence in patients treated with tumor enucleation for clinically intracapsular renal cell carcinomas (RCCs). METHODS AND MATERIALS PC status was analyzed in 304 consecutive patients with single intracapsular RCC. Degree and side of capsule penetration if present were evaluated. Mean (median, range) follow-up was 49 months (46, 25-69). Local recurrence rate, progression-free survival (PFS), and cancer-specific survival were the main outcomes. Statistical analyses included the Kaplan-Meier method, log-rank test, and univariate and multivariate Cox regression models. RESULTS Overall, 51% of RCCs had intact PC and free from neoplastic invasion (PC-), 34.9% had capsular penetration on the parenchymal side (PCK), and 14.1% had tumor invasion on the perirenal fat tissue side (PCF). None of the patients had positive surgical margins. The 5-year PFS rates for tumors PC-, PCK, and PCF were 97.5%, 96.7%, and 77.1%, respectively (P<0.0001). The multivariate Cox model showed PCF to be the sole significant independent predictor of PFS, whereas patients who had PCK did not present a significant increased risk in developing recurrence. CONCLUSIONS Tumor enucleation is an oncologically safe nephron-sparing surgery technique. PCF is a significant and independent predictor of tumor recurrence in patients with clinically intracapsular RCCs scheduled for nephron-sparing surgery. PCK does not predict the risk of recurrence.

Prognostic Role of Histological Necrosis for Nonmetastatic Clear Cell Renal Cell Carcinoma: Correlation With Pathological Features and Molecular Markers

PURPOSE We defined the prognostic role of tumor necrosis and its extent in nonmetastatic clear cell renal cell carcinoma. Also, we further investigated its pathogenesis by correlating this tumor feature with other pathological characteristics and molecular markers related to the von Hippel Lindau-hypoxia inducible factor pathway and to tumor proliferation. MATERIALS AND METHODS A total of 213 patients with nonmetastatic clear cell renal cell carcinoma were evaluated. Mean followup was 66 months. The presence and extent of histological necrosis were correlated with clinicopathological factors, Ki-67 antigen expression calculated by the MIB-1 (Ki-67 antibody) index, pVHL, HIF-1alpha, the tumor infiltrating lymphocyte subset and cancer specific survival. RESULTS Histological necrosis was present in 63.8% of clear cell renal cell carcinoma cases. Necrosis was significantly associated with grade and the degree of tumor infiltrating lymphocytes, while its extent correlated significantly with grade, the degree of tumor infiltrating lymphocytes and stage. Tumor necrosis was a significant prognostic factor, which was confirmed even when limiting analysis to patients with intracapsular renal cell carcinoma. On multivariate analysis histological necrosis was not an independent predictor of cancer specific survival. The extent of tumor necrosis was not a significant prognostic factor. The presence and extent of histological necrosis was not associated with high Ki-67 expression and it did not correlate with pVHL expression or with nuclear and cytoplasmic HIF-1alpha expression. CONCLUSIONS Based on our results we cannot support histological necrosis and its extent as prognostic factors for clear cell renal cell carcinoma. Efforts should be made to develop nomograms that use routinely available and objective predictor variables. The precise mechanism that causes tumor necrosis remains unknown but the host immune response might significantly contribute to its development.

An Open, Randomised, Multicentre, Phase 3 Trial Comparing the Efficacy of Two Tamoxifen Schedules in Preventing Gynaecomastia Induced by Bicalutamide Monotherapy in Prostate Cancer Patients

BACKGROUND Bicalutamide monotherapy is a valuable option for prostate cancer (PCa) patients who wish to avoid the consequences of androgen deprivation; however, this treatment induces gynaecomastia and mastalgia in most patients. Tamoxifen is safe and effective in preventing breast events induced by bicalutamide monotherapy without affecting antitumor activity, but possible interference between bicalutamide and tamoxifen remains a matter of concern. To reduce the exposure to tamoxifen, we considered the putative advantages of weekly administration. OBJECTIVE To compare the efficacy of two different schedules of tamoxifen in preventing breast events. Toxicity, prostate-specific antigen behaviour, and sexual-functioning scores were also evaluated. DESIGN, SETTING, AND PARTICIPANTS This was a noninferiority trial. From December 2003 to February 2006, 80 patients with localised/locally advanced or biochemically recurrent PCa who were also candidates for bicalutamide single therapy were randomised to receive two different schedules of tamoxifen: daily (n=41) and weekly (n=39). Median follow-up was 24.2 mo. INTERVENTION Daily bicalutamide (150 mg) plus daily tamoxifen 20mg continuously (daily group) or the same but with tamoxifen at 20mg weekly after the first 8 wk of daily treatment (weekly group). Three patients in the weekly group and one in the daily group were discontinued for adverse events. MEASUREMENTS For gynaecomastia, we used ultrasonography. For mastalgia and sexual functioning, we used questionnaires. RESULTS AND LIMITATIONS Gynaecomastia developed in 31.7% of patients in the daily group and in 74.4% of patients in the weekly group (p<0.0001), and it was more severe in patients who switched to weekly tamoxifen (p=0.001). Mastalgia occurred in 12.2% and 46.1% of patients, respectively (p=0.001). There were no major differences among treatment schedules relative to sexual functioning scores and incidence and severity of adverse events. No differences between groups in PSA behaviour and disease progression have been detected so far. CONCLUSIONS This study demonstrated that tamoxifen 20mg/wk is inferior to tamoxifen 20mg/d in preventing the incidence and severity of bicalutamide-induced breast events. The safety and efficacy of tamoxifen at the common daily dose of 20mg for the prophylaxis of bicalutamide-induced breast events were confirmed.