Results from phase 3 study of 89Zr-DFO-girentuximab for PET/CT imaging of clear cell renal cell carcinoma (ZIRCON).
Brian ShuchAllan J. PantuckJean‐Christophe BernhardMichael A. MorrisViraj A. MasterAndrew M. ScottCharles Van PraetClément BaillyTamer AksoyRobin MerkxDavid M. SchusterSze Ting LeeNeeta Pandit‐TaskarAlice C. FanLibuse TauchmanovàPhillip AllmanKavita VadaliColin HaywardPeter Mulders
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LBA602 Background: The increasing detection of renal masses presents a significant patient management challenge. Diagnostic options include cross-sectional imaging, which cannot reliably differentiate benign and malignant renal masses, and biopsy, which is invasive and subject to sampling errors. These limitations highlight the unmet need for accurate noninvasive techniques to guide patient management. Girentuximab is a monoclonal antibody that targets carbonic anhydrase IX (CAIX), an enzyme highly expressed in clear cell renal carcinoma (ccRCC). Radiolabeled 89 Zr-DFO-girentuximab (TLX250-CDx) is highly specific for CAIX and can aid differentiation between ccRCCs and other renal lesions. The ZIRCON study evaluated the performance of TLX250-CDx PET/CT for detection of ccRCC in adult patients with indeterminate renal masses (IDRM). Methods: ZIRCON was an open-label, multicenter clinical trial. Patients with an IDRM (≤ 7 cm; tumor stage cT1) who were scheduled for partial nephrectomy within 90 days from planned TLX250-CDx administration were eligible. Enrolled patients received a single dose of TLX250-CDx IV (37 MBq ± 10%; 10 mg girentuximab) on Day 0 and underwent PET/CT imaging on Day 5 (± 2 days) prior to surgery. Blinded central histology review determined ccRCC status. The coprimary objectives were to evaluate both the sensitivity and specificity of TLX250-CDx PET/CT imaging in detecting ccRCC in patients with IDRM, using histology as the standard of truth. Key secondary objectives included sensitivity and specificity of TLX250-CDx PET/CT imaging in the subgroup of patients with IDRM ≤ 4 cm (cT1a). Other secondary objectives included positive and negative predictive values, safety, and tolerability. The Wilson 95% confidence intervals (CI) lower bound for sensitivity and specificity had to be > 70% and 68% respectively for ≥ 2 independent readers to declare the study successful. Results: 300 patients received TLX250-CDx; mean age was 62 ± 12 y; 71% were males. Of 288 patients with central histopathology of surgical samples, 193 (67%) had ccRCC, and 179 (62%) had CT1a; Of 284 evaluable patients included in primary analysis, the average across all 3 readers for sensitivity and specificity was 86% [80%, 90%] and 87% [79%, 92%] respectively for coprimary endpoints; and 85% [77%, 91%] and 90% [79%, 95%] respectively for key secondary endpoints. For all readers, the lower boundaries of 95% CI for coprimary and key secondary endpoints were > 75%. For all evaluable patients, positive and negative predictive values were ≥ 91.7% and ≥ 73.7%, respectively. Of 263 treatment-emergent adverse events (TEAEs), 2 TEAEs were treatment related. Conclusions: This study confirms that TLX250-CDx PET/CT is well tolerated and can accurately and noninvasively identify ccRCC, with promising utility for designing best management approaches for patients with IDRM. Clinical trial information: NCT03849118 .Keywords:
Histology
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Objectives To compare the recurrence‐free survival of partial nephrectomy and radical nephrectomy in patients with non‐metastatic pathological T3a renal cell carcinoma. Methods We reviewed the records of 3567 patients who had undergone a nephrectomy for renal cell carcinoma at five institutions in K orea from J anuary 2000 to D ecember 2010. The clinical data of 45 patients with pathological T3a renal cell carcinoma in the partial nephrectomy group were compared with 298 patients with pathological T3a renal cell carcinoma in the radical nephrectomy group. The effects of surgical methods on recurrence‐free survival were assessed by a multivariate C ox proportional hazard analysis. All comparisons were repeated in subgroup analysis on 63 clinical T1a patients with tumors ≤4 cm. Results During a median 43‐month follow‐up period, disease recurrence occurred in two patients (4.4%) in the partial nephrectomy group, and 94 patients (31.5%) in the radical nephrectomy group. The results from a multivariate model showed that radical nephrectomy was a significant predictor of recurrence. However, in subgroup analysis that included 63 clinical T1a pathological T3a patients, the recurrence‐free survival rates were not significantly different between the two cohorts. The renal function was significantly better preserved in the partial nephrectomy cohort than in the radical nephrectomy cohort. Conclusions Partial nephrectomy provides similar recurrence‐free survival outcomes compared with radical nephrectomy in patients with clinical T1a pathological T3a renal cell carcinoma. However, there seems to be a higher risk of recurrence for large pathological T3a tumors treated by radical nephrectomy compared with small tumors treated by partial nephrectomy. Thus, large tumors with the same pathological T3a renal cell carcinoma grade could have hidden aggressive features.
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Abstract Background Nephrectomy is considered the backbone of managing patients with localized and selected metastatic renal cell carcinoma (mRCC). The prognostic role of nephrectomy has been widely investigated with cytokines and targeted therapy, but it is still unclear in the immunotherapy era. Methods We investigated the Meet-URO-15 study dataset of 571 pretreated mRCC patients receiving nivolumab as second or further lines about the prognostic role of the previous nephrectomy (received in either the localized or metastatic setting) in the overall population and according to the Meet-URO score groups. Results Patients who underwent nephrectomy showed a significantly reduced risk of death (HR 0.44, 95% CI 0.32–0.60, p < 0.001) with a longer median overall survival (OS) (35.9 months vs 12.1 months), 1-year OS of 71.6% vs 50.5% and 2-years OS of 56.5% vs 22.0% compared to those who did not. No significant interaction between nephrectomy and the overall five Meet-URO score risk groups was observed ( p = 0.17). It was statistically significant when merging group 1 with 2 and 3 and group 4 with 5 ( p = 0.038) and associated with a longer OS for the first three prognostic groups ( p < 0.001), but not for groups 4 and 5 ( p = 0.54). Conclusions Our study suggests an overall positive impact of the previous nephrectomy on the outcome of pretreated mRCC patients receiving immunotherapy. The clinical relevance of cytoreductive nephrectomy, optimal timing and patient selection deserves further investigation, especially for patients with Meet-URO scores of 1 to 3, who are the once deriving benefit in our analyses. However, that benefit is not evident for IMDC poor-risk patients (including the Meet-URO score groups 4 and 5) and a subgroup of IMDC intermediate-risk patients defined as group 4 by the Meet-URO score.
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Parenchyma
Hilum (anatomy)
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Partial nephrectomy has been considered an effective and efficient method in the treatment of localized renal cell carcinoma. Herein, we retrospectively review our experience with partial nephrectomy in the treatment of localized renal cell carcinoma and compared it with patients who received radical nephrectomy.From 1982 to 2005, 35 patients who received partial nephrectomy for localized renal cell carcinoma were enrolled in this study. Ten patients were female (28.6%). The median age was 70 years (range, 42-82 years). Sixteen (45.7%) patients had pathologic T1a tumors; 17 (48.6%) patients had pathologic T1b tumors and 2 (5.7%) patients had pathologicT2 tumor (7cm). In the meantime, 128 patients who had T1N0M0 renal cell carcinoma and who received radical nephrectomy were assigned to a control group. Thirty-nine patients (30.5%) were female in this group. The median age was 62 years (range, 30-83 years). The tumor characteristics, location, surgical techniques and patient survival were subsequently compared.The median tumor size in the partial nephrectomy group was 3.9cm (range, 1.5-7.0cm), and it was 4.5cm (range, 1-6.5cm) in radical nephrectomy group. The tumor size was smaller in the partial nephrectomy group (p = 0.003). Themedian follow-up period was 4.38 years (range, 0.05-17.99 years) in the partial nephrectomy group and 5.66 years (range, 0.01-22.25 years) in the radical nephrectomy group. There was no local recurrence or distant metastasis in the partial nephrectomy group. The 5-year overall survival was 85.0% compared with 91.4% in the radical nephrectomy group (p = 0.126). The 5-year disease specific survival in the partial nephrectomy group was 100%. The postoperative serum creatinine level increased to >2.0mg/dL in 5 (14.3%) patients in the partial nephrectomy group, but no patient needed hemodialysis during follow-up.From our review, partial nephrectomy is safe and provides excellent disease control in the treatment of localized renal cell carcinoma in selected patients. Renal function preservation was observed in the partial nephrectomy group, while the operated kidney showed functioning in the follow-up nuclear medicine survey.
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Distant metastasis
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We used a large, population based registry to assess whether a difference in overall and cardiovascular survival may exist between radical nephrectomy and partial nephrectomy for renal cell carcinoma 2 cm or less.From the SEER (Surveillance, Epidemiology and End Results) registry we identified 4,216 patients with histologically confirmed renal cell carcinoma 2 cm or less who were treated with partial or radical nephrectomy. Patient and tumor characteristics were compared between the 2 patient groups. Multivariate logistic regression was done to predict the odds of undergoing radical nephrectomy. Cardiovascular survival and overall survival were compared between the 2 cohorts, adjusting for patient and tumor characteristics.Overall 2,301 patients (55%) underwent partial nephrectomy. Partial nephrectomy use steadily increased during the study period from 27% of all cases in 1998 to 66% in 2007. Patients who underwent partial nephrectomy were an average of 2.5 years younger than those treated with radical nephrectomy (56.4 vs 58.9 years, p <0.001). They were more likely to be white and from the western or northeastern United States. Older age was the only independent predictor of radical nephrectomy (OR 1.02, 95% CI 1.01-1.03). When controlling for patient characteristics and surgery year, radical nephrectomy was associated with worse overall mortality (HR 2.24, 95% CI 1.75-2.84) and cardiovascular mortality (HR 2.53, 95% CI 1.51-4.23).Radical nephrectomy is associated with worse overall and cardiovascular survival compared to partial nephrectomy in patients with localized renal cell carcinoma 2 cm or less. These findings justify the widespread application of nephron sparing techniques to treat localized kidney cancer.
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