Surgical treatment of atypical metastasis from renal cell carcinoma (RCC).

UNLABELLED: What's known on the subject? and What does the study add? The interest in metastatic renal cell carcinoma has increased in the last few years, mainly due to the advent of targeted therapies, but metastasectomy remains the sole therapy that can lead to a complete and durable regression, even if only in a minority of patients. The literature reports quite large series of metastasectomies for the most common sites of metastasis, e.g. lung, liver, bone, adrenal and brain, whereas little is known about the management of metastasis in 'atypical' sites. The prognosis of patients submitted to metastasectomy for a metastasis in an atypical site is equivalent to patients with lung metastasis. The characteristics of the primary tumour in these patients are not indicative, but atypical metastasis (AM) are often located in superficial sites and frequently associated with other metastases. So, physical examination should be included in all follow-up regimens and a complete re-staging should be performed after the diagnosis of an AM. OBJECTIVE: • To review the clinical characteristics and oncological results in patients submitted to surgical removal of metastasis from renal cell carcinoma (RCC) in atypical sites (atypical metastasis [AM], i.e. metastasis in sites other than the chest, liver, bone, adrenal, brain, kidney, and lymph nodes), compared with patients submitted to metastasectomy due to a lung metastasis (LM). PATIENTS AND METHODS: • From an institutional database of ≈1800 patients surgically treated for a RCC, we retrospectively identified 37 cases that had undergone metastasectomy for AM and 57 operated for LM. • Clinicopathological features of the primary RCC and metastasis, and cancer-specific survival (CSS) computed from the time of metastasectomy of patients with AM and LM, were compared. • A univariate and multivariable analysis applying a Cox regression model was used to evaluate CSS. RESULTS: • The patients with AM and LM were followed for an average of 40.8 and 50.7 months from metastasectomy, respectively (P= 0.372). • There were no significant differences in the characteristics of the primary tumour between patients with AM and LM. • In the cases with AM and LM the diagnosis was simultaneous with that of the primary tumour in 32.4% and 24.6%, (P= 0.40) respectively, and, when metachronous, occurred at an average delay of 53.4 and 44.3 months (P= 0.370). • More frequently in the cases with AM other metastases had been diagnosed in the previous medical history (35.2 vs 8.8%, P= 0.001) or simultaneously (48.6 vs 8.8%, P= 0.001). • CSS from metastasectomy was affected by the synchronicity in diagnosis between metastasis and primary tumour, and by the simultaneous presence of other metastases, while the type of metastasis (AM vs LM) did not affect CSS. In fact, metastasectomy in AM was as effective as in LM. CONCLUSION: • AM are an exceptional presentation of metastatic RCC, but the role of surgery is similar to that of pulmonary metastasis. In these cases, metastasectomy is accepted as possible care, and in AM the CSS after metastasectomy is similar.

[T&G: an elementary integrated prognostic system for renal carcinoma N0 M0]. / T&G: un sistema prognostico integrato elementare per il carcinoma renale N0 M0.

INTRODUCTION: 25-30% of patients with renal cell carcinoma (RCC) develop metastatic progression during follow up. For this reason many prognostic systems have been developed to try to predict the possibility of recurrence. Unfortunately these systems are often complex in daily use. PATIENT AND METHODS: 1089 were selected from a total of 1985 patients undergoing surgery for renal cell cancer. We have excluded patients with a benign diagnosis, lymph node or distant metastases at diagnosis, with no radical surgery (R1) and those with follow up judged insufficient (<24 months). For each patient a score was defined after evaluating the histological examination of surgical specimens. This score was called T&G and it was equal to the sum of the T pathological (1 for T1, 2 for T2, 3 for T3a, b, c, 4 for T4) and the G according to Fuhrman (1 for G1, 2 for G2, etc.). The range is between 2 and 8. It was then evaluated the disease-free survival according to T & G score to stratify patients into risk classes. RESULTS: During follow-up we had recurrent disease in 246 cases (22.6%; 167 metastases in a single location, 34 local recurrences, 45 metastases) after surgery at a mean distance of 35.6 months (2-205). After comparing each one of the disease free survival curves, we have identified three classes of risk: low risk (T & G 2 and 3), intermediate risk (T & G 4-5), high risk (T & G 6-7-8). We have obtained statistically significant differences between the three classes of risk. The rate of progression was 8.9% for the class of low risk to 48% of the high risk class. The average time (in months) of disease progression decrease from 47 for LR class to 37 for IR up to 29 for a HR Class. DISCUSSION: The T & G score is an extremely basic prognostic system but at the same time it allows an accurate prognostic discrimination in patients with N0 M0 RCC, as demonstrated by the significant differences in the rates and time of progression and disease-free survival.

[Results of targeted therapies for m1 renal cell carcinoma: our experience]. / Risultati della target therapy nel carcinoma renale a cellule chiare m1: la nostra esperienza.

INTRODUCTION: Since a few years ago no effective medical therapies were available to cure metastatic renal cell carcinoma (RCC). Nowadays, encouraging preliminary results support some new therapeutic agents, collectively named as targeted therapies (TT). This paper reviews our experience with the use of TT in the setting of RCC with metastasis at the diagnosis. MATERIAL AND METHODS: Retrospective evaluation of the data of 24 patients (7 females, 17 males, median age: 59aa) affected by clear cell RCC with distant metastatis at diagnosis, treated with TT from 2005 to 2012.20 of the 24 patients (83,3%) underwent preliminary cytoreductive nephrectomy, whereas for the others a percutaneous biopsy of the renal tumor was obtained. 5 (20.8%) patients received an immunotherapy with IL-2 or IFN and then a TT due to a progression. Schedules were applied following heterogeneous regimens along the period of data collection (randomized clinical trial, expanded access, standard indication). Response has been evaluated by RECIST criteria. RESULTS: As first-line therapy of TT 18 patients received Sunitinib, 4 Sorafenib, 2 Temsirolimus; 11 received a second-line (8 Sorafenib, 2 Sunitinib, 1 Everolimus); 6 received also a third-line (5 Everolimus, 1 Tensirolimus). At last available control, after a mean follow up time of 13,7 months (1-29) a progressive disease was present in 12 cases (50%), a stable disease in 6 (25%), a reduction of the disease in 4 (16.5%); 7 patients (29.5%) died; overall mean survival of the entire group was 14,7 months. Even if the study suffers from the limitations related to the small number of cases and the retrospective design, seems that no factors played a role in determining the response to theraphy. CONCLUSIONS: The results of TT in clinical practice resemble the ones from randomised clinical trials. It's extremely hard to predict the response to treatment.