Andrea Minervini

Validation of the 2009 TNM Version in a Large Multi-Institutional Cohort of Patients Treated for Renal Cell Carcinoma: Are Further Improvements Needed?

BACKGROUND A new edition of the TNM was recently released that includes modifications for the staging system of kidney cancers. Specifically, T2 cancers were subclassified into T2a and T2b (< or =10 cm vs >10 cm), tumors with renal vein involvement or perinephric fat involvement were classified as T3a cancers, and those with adrenal involvement were classified as T4 cancers. OBJECTIVE Our aim was to validate the recently released edition of the TNM staging system for primary tumor classification in kidney cancer. DESIGN, SETTING, AND PARTICIPANTS Our multicenter retrospective study consisted of 5339 patients treated in 16 academic Italian centers. INTERVENTION Patients underwent either radical or partial nephrectomy. MEASUREMENTS Univariable and multivariable Cox regression models addressed cancer-specific survival (CSS) after surgery. RESULTS AND LIMITATIONS In the study, 1897 patients (35.5%) were classified as pT1a, 1453 (27%) as pT1b, 437 (8%) as pT2a, 153 (3%) as pT2b, 1059 (20%) as pT3a, 117 (2%) as pT3b, 26 (0.5%) as pT3c, and 197 (4%) as pT4. At a median follow-up of 42 mo, 786 (15%) had died of disease. In univariable analysis, patients with pT2b and pT3a tumors had similar CSS, as did patients with pT3c and pT4 tumors. Moreover, both pT3a and pT3b stages included patients with heterogeneous outcomes. In multivariable analysis, the novel classification of the primary tumor was a powerful independent predictor of CSS (p for trend <0.0001). However, the substratification of pT1 tumors did not retain an independent predictive role. The major limitations of the study are retrospective design, lack of central pathologic review, and the small number of patients included in some substages. CONCLUSIONS The recently released seventh edition of the primary tumor staging system for kidney tumors is a powerful predictor of CSS. However, some of the substages identified by the classification have overlapping prognoses, and other substages include patients with heterogeneous outcomes. The few modifications included in this edition may have not resolved the most critical issues in the previous version.

Outcome of penile prosthesis implantation for treating erectile dysfunction: experience with 504 procedures.

To evaluate the outcome of penile prosthesis surgery for different types of prosthesis.

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.

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.

Correlation of upper-tract cytology, retrograde pyelography, ureteroscopic appearance, and ureteroscopic biopsy with histologic examination of upper-tract transitional cell carcinoma.

PURPOSE To determine the accuracy of radiographic studies, ureteroscopy, biopsy, and cytology in predicting the histopathology of upper-tract transitional cell carcinoma (TCC). MATERIALS AND METHODS From 1998 to 2006, 46 upper-tract lesions were diagnosed ureteroscopically and underwent nephroureterectomy, and 30 of them were subjected to direct ureteroscopic inspection and biopsy. Fresh samples were delivered to the cytopathology laboratory and histology samples were prepared whenever visible tissue was present. Radiological, ureteroscopic, cytology, and biopsy data were compared to the actual grades and stages of these 30 surgical specimens. RESULTS Retrograde ureteropyelography was suggestive of malignancy in 29 of 30 cases, but did not predict the grade or stage accurately. Cytology was positive for malignancy in 21 of 30 cases (70%). Grading of ureteroscopic specimens was possible in all cases. At nephroureterectomy two cases were found to have no tumor (T(0)). Of the remaining 28 cases, the biopsy grade proved to be identical in 21 (75%). Grade 1 or 2 ureteroscopic specimens had a low-stage (T(0), T(a), or T(1)) tumor in 17 of 25 (68%); in contrast, 3 of 5 (60%) high-grade specimens had invasive tumor (T(2) or T(3)). For patients with grade 2 ureteroscopic specimens, combining exfoliated cell cytology and biopsy grade improved the accuracy in predicting high-stage and high-grade disease. CONCLUSIONS This study confirms previous findings that ureteroscopic inspection and biopsy provides accurate information regarding the grade and stage of upper-tract TCC. Combining exfoliated cell cytology improves the predictive power of biopsy grade 2 disease for high-risk specimen grade and stage. Our data suggest that ureteroscopic findings may predict muscle invasion.

Elective partial nephrectomy is equivalent to radical nephrectomy in patients with clinical T1 renal cell carcinoma: results of a retrospective, comparative, multi‐institutional study

Study Type – Therapy (cohort)

A multicentre matched‐pair analysis comparing robot‐assisted versus open partial nephrectomy

To compare the perioperative, pathological and functional outcomes in two contemporary, large series of patients in different institutions and who underwent open partial nephrectomy (OPN) or robot‐assisted PN (RAPN) for suspected renal tumours.

Chromophobe renal cell carcinoma (RCC): oncological outcomes and prognostic factors in a large multicentre series

Study Type – Outcomes (cohort)

Features associated with recurrence beyond 5 years after nephrectomy and nephron-sparing surgery for renal cell carcinoma: Development and internal validation of a risk model (PRELANE score) to predict late recurrence based on a large multicenter database (CORONA/SATURN Project)

BACKGROUND Approximately 10-20% of recurrences in patients treated with nephrectomy for renal cell carcinoma (RCC) develop beyond 5 yr after surgery (late recurrence). OBJECTIVE To determine features associated with late recurrence. DESIGN, SETTING, AND PARTICIPANTS A total of 5009 patients from a multicenter database comprising 13 107 RCC patients treated surgically had a minimum recurrence-free survival of 60 mo (median follow-up [FU]: 105 mo [range: 78-135]); at last FU, 4699 were disease free (median FU: 103 mo [range: 78-134]), and 310 patients (6.2%) experienced disease recurrence (median FU: 120 mo [range: 93-149]). INTERVENTIONS Patients underwent radical nephrectomy or nephron-sparing surgery. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Multivariable regression analyses identified features associated with late recurrence. Cox regression analyses evaluated the association of features with cancer-specific mortality (CSM). RESULTS AND LIMITATIONS Lymphovascular invasion (LVI) (odds ratio [OR]: 3.07; p<0.001), Fuhrman grade 3-4 (OR: 1.60; p=0.001), and pT stage >pT1 (OR: 2.28; p<0.001) were significantly associated with late recurrence. Based on accordant regression coefficients, these parameters were weighted with point values (LVI: 2 points; Fuhrman grade 3-4: 1 point, pT stage >1: 2 points), and a risk score was developed for the prediction of late recurrences. The calculated values (0 points: late recurrence risk 3.1%; 1-3 points: 8.4%; 4-5 points: 22.1%) resulted in a good-, intermediate- and poor-prognosis group (area under the curve value for the model: 70%; 95% confidence interval, 67-73). Multivariable Cox regression analysis showed LVI (HR: 2.75; p<0.001), pT stage (HR: 1.24; p<0.001), Fuhrman grade (HR: 2.40; p<0.001), age (HR: 1.01; p<0.001), and gender (HR: 0.71; p=0.027) to influence CSM significantly. Limitations are based on the multicenter and retrospective study design. CONCLUSIONS LVI, Fuhrman grade 3/4, and a tumor stage >pT1 are independent predictors of late recurrence after at least 5 yr from surgery in patients with RCC. We developed a risk score that allows for prognostic stratification and individualized aftercare of patients with regard to counseling, follow-up scheduling, and clinical trial design.