Oligo metastatic renal cell carcinoma: stereotactic body radiation therapy, if, when and how?

BACKGROUND AND PURPOSE: Renal cell carcinoma (RCC) has traditionally been considered radioresistant with a limited role for conventional fractionation as a local approach. Nevertheless, since the appearance of stereotactic body radiation therapy (SBRT), radiotherapy (RT) has been increasingly employed in the management of metastatic RCC (mRCC). The aim of this study was to evaluate the role of SBRT for synchronous and metachronous oligo metastatic RCC patients in terms of local control, delay of systemic treatment, overall survival and toxicity. PATIENTS AND METHODS: A Monocentric single institution retrospective data collection was performed. Inclusion criteria were: (1) oligo-recurrent or oligo-progressive disease (less than 5 metastases) in mRCC patients after radical/partial nephrectomy or during systemic therapy, (2) metastasectomy or other metastasis-directed, rather than SBRT not feasible, (3) any contraindication to receive systemic therapy (such as comorbidities), (4) all the histologies were included, (5) available signed informed consent form for treatment. Tumor response and toxicity were evaluated using the response evaluation criteria in solid tumors and the Common Terminology Criteria for Adverse Events version 4.03, respectively. Progression-free survival in-field and out-field (in-field and out-field PFS) and overall survival (OS) were calculated via the Kaplan-Meier method. The drug treatment-free interval was calculated from the start of SBRT to the beginning of any systemic therapy. RESULTS: From 2010 to December 2018, 61 patients with extracranial and intracranial metastatic RCC underwent SBRT on 83 lesions. Intracranial and extracranial lesions were included. Forty-five (74%) patients were treated for a solitary metastatic lesion. Median RT dose was 25 Gy (range 10-52) in 5-10 fractions. With a median follow-up of 2.3 years (range 0-7.15), 1-year in-field PFS was 70%, 2-year in-field PFS was 55%. One year out-field PFS was 39% and 1-year OS was 78%. Concomitant systemic therapy was employed for only 11 (18%) patients, for the others 50 (82%) the drug treatment-free rate was 70% and 50% at 1 and 2 years, respectively. No > G1 acute and late toxicities were reported. CONCLUSION: The pattern of failure was pre-dominantly out-of-field, even if the population was negatively selected and the used RT dose could be considered palliative. Therefore, SBRT appears to be a well-tolerated, feasible and safe approach in oligo metastatic RCC patients with an excellent in-field PFS. SBRT might play a role in the management of selected RCC patients allowing for a delay systemic therapy begin (one out of two patients were free from new systemic therapy at 2 years after SBRT). Further research on SBRT dose escalation is warranted.

A novel nomogram predicting lymph node invasion among patients with prostate cancer: The importance of extracapsular extension at multiparametric magnetic resonance imaging.

PURPOSE: To develop a novel risk tool that allows the prediction of lymph node invasion (LNI) among patients with prostate cancer (PCa) treated with robot-assisted radical prostatectomy (RARP) and extended pelvic lymph node dissection (ePLND). METHODS: We retrospectively identified 742 patients treated with RARP + ePLND at a single center between 2012 and 2018. All patients underwent multiparametric magnetic resonance imaging (mpMRI) and were diagnosed with targeted biopsies. First, the nomogram published by Briganti et al. was validated in our cohort. Second, three novel multivariable logistic regression models predicting LNI were developed: (1) a complete model fitted with PSA, ISUP grade groups, percentage of positive cores (PCP), extracapsular extension (ECE), and Prostate Imaging Reporting and Data System (PI-RADS) score; (2) a simplified model where ECE score was not included (model 1); and (3) a simplified model where PI-RADS score was not included (model 2). The predictive accuracy of the models was assessed with the receiver operating characteristic-derived area under the curve (AUC). Calibration plots and decision curve analyses were used. RESULTS: Overall, 149 patients (20%) had LNI. In multivariable logistic regression models, PSA (OR: 1.03; P= 0.001), ISUP grade groups (OR: 1.33; P= 0.001), PCP (OR: 1.01; P= 0.01), and ECE score (ECE 4 vs. 3 OR: 2.99; ECE 5 vs. 3 OR: 6.97; P< 0.001) were associated with higher rates of LNI. The AUC of the Briganti et al. model was 74%. Conversely, the AUC of model 1 vs. model 2 vs. complete model was, respectively, 78% vs. 81% vs. 81%. Simplified model 1 (ECE score only) was then chosen as the best performing model. A nomogram to calculate the individual probability of LNI, based on model 1 was created. Setting our cut-off at 5% we missed only 2.6% of LNI patients. CONCLUSIONS: We developed a novel nomogram that combines PSA, ISUP grade groups, PCP, and mpMRI-derived ECE score to predict the probability of LNI at final pathology in RARP candidates. The application of a nomogram derived cut-off of 5% allows to avoid a consistent number of ePLND procedures, missing only 2.6% of LNI patients. External validation of our model is needed.

The surgical management of patients with clinical stage T4 bladder cancer: A single institution experience.

INTRODUCTION: Patients with clinical T4 (cT4) bladder cancer (BCa) infrequently undergo radical cystectomy (RC). We investigated the reliability of preoperative clinical staging, perioperative and survival outcomes in patients treated with RC due to cT4a-b BCa disease at a single tertiary care institution. METHODS: The study relied on 917 BCa patients treated with RC and pelvic lymph node dissection (PLND) at a single institution between January 1995 and December 2012. We compared the accuracy of the clinical assessment with final pathology results. Moreover, we evaluated perioperative outcomes, complication rates and survival after surgery. RESULTS: The median follow-up was 62 months. Overall, 74 (8.1%) patients presented cT4 stage at preoperative evaluation. Conversely, a pathological T4 disease was confirmed only in 68.9% patients staged initially as cT4. No differences were recorded in complications, 30 days readmission or 30 days death rates between cT1-T3 vs. cT4a vs. cT4b (p > 0.1). At multivariable Cox regression analyses predicting cancer specific mortality, clinical T4 stage vs. clinical T1-2, clinical T3 stage vs. clinical T1-2 and age were predictors of worst survival after RC (all p < 0.04). CONCLUSIONS: We recorded poor concordance between preoperative imaging and pathology in cT4 patients. No differences in major perioperative outcomes and acceptable survival expectancies were reported in patients treated for cT4 disease.

Determinants of long-term survival of patients with locally advanced prostate cancer: the role of extensive pelvic lymph node dissection.

BACKGROUND: The therapeutic effect of pelvic lymph node dissection (PLND) during radical prostatectomy (RP) due to prostate cancer (PCa) is still under debate. We aimed at assessing the impact of more extensive PLND on cancer-specific mortality (CSM) in patients treated with surgery for locally advanced PCa. METHODS: We examined data of 1586 pT3-T4 PCa patients treated with RP and extended PLND between 1987 and 2012 at a tertiary referral care center. Univariable and multivariable Cox regression analyses tested the relationship between the number of nodes removed and CSM rate, after adjusting for potential confounders. Survival estimates were based on the multivariable models. RESULTS: The average number of nodes removed was 19 (median: 17; interquartile range: 11-23). Mean and median follow-up were 80 and 72 months, respectively. At multivariable analyses, Gleason score 8-10 (hazard ratio (HR): 2.5) and a higher number of positive nodes (HR: 1.06) were independently associated with higher CSM rate (all P<0.05). Conversely, higher number of removed LNs (HR: 0.94) and adjuvant radiotherapy (HR: 0.54) were independent predictors of lower CSM rates (all P⩽0.03). CONCLUSIONS: In pT3-T4 PCa patients, removal of a higher number of LNs during RP was associated with higher cancer-specific survival rates. This supports the role of more extensive PLNDs in this patient group. Further prospective studies are needed to validate our findings.