Twenty-year survival after iterative surgery for metastatic renal cell carcinoma: A case report and review of literature

Table 1 Timeline of interventions and outcomes

1998 December	Sudden macroscopic hematuria with pain. Diagnosis of neoplasm of the left kidney without distant metastases. Radical left nephrectomy, with uneventful postoperative course. At pathological examination: Clear cell type, infiltrating RCC, measuring 95 mm × 55 mm × 50 mm, without LyMs, without involvement of the perirenal adipose tissue, Fuhrman grade 3, with negative surgical margins. No adjuvant systemic therapy
1999 January to 2004 October	Regular, uneventful follow-up
2004, November to December	At periodic surveillance CECT scan: LuM in the inferior lobe of the right lung, measuring 15 mm, with LyMs measuring up to 45 mm. CT guided biopsy of an enlarged mediastinal lymph node: Recurrence of ccRCC. IMDC Risk Score: 0. Multiple pulmonary metastasectomies of the right lung and radical mediastinal lymphadenectomy, with uneventful postoperative course. At pathological examination: 9 LuMs measuring up to 15 mm, with mediastinal LyMs
2005, January to April	Postoperative chemo-immunotherapy with 5-FU, 200 mg/m2 per day intravenously for 3 wk every 4 wk, IFN-α, 3 MU subcutaneously on day 1, 2, 8, 9, 15, 16, and IL-2, 3 MU subcutaneously on day 2, 3 ,4, 5, 6, 9, 10, 11, 12, 13, 15, 17, 18, 19, 20
2005 May to 2006 March	IL-2, 3 MU subcutaneously thrice weekly
2006 April to 2007 January	Regular, uneventful follow-up
2007, February to March	At surveillance CECT scan: Multiple, bilateral millimetric pulmonary nodules suggestive of metastasis; PaM in the body of the pancreas, measuring 55 mm × 35 mm (Figure 1A). Systemic therapy with oral sunitinib 50 mg/d, subsequently reduced to 37.5 mg/d because of severe stomatitis and dental pain
2007 July to August	At CECT scan: Significant volumetric reduction of the pulmonary nodules and of the PaM (Figure 1B). Distal pancreatectomy with splenectomy (Figure 1C), with uneventful postoperative course. At pathological examination: Metastatic ccRCC, Fuhrman grade 1-2, with intratumoral necrosis and calcifications, infiltrating the splenic vein, without LyMs and with negative surgical margins. Maintenance of systemic therapy with oral sunitinib, 37.5 mg/d
2007 October	At CECT scan: Disappearance of the multiple, bilateral millimetric pulmonary nodules
2007 October to 2010 October	Maintenance of systemic therapy with oral sunitinib, 37.5 mg/d. Regular, uneventful follow-up
2010, November to December	At CECT scan and subsequent MRI with Gd-EOB-DTPA: 3 millimetric liver nodules suggestive of metastasis. Systemic therapy shifted to oral everolimus, 10 mg/d
2011, January to June	Maintenance of systemic therapy with oral everolimus, 10 mg/d
2011 July	At CECT scan: Progression of the LiMs. Systemic therapy shifted to oral sorafenib, 800 mg/d
2011 August to 2012 June	Further slow progression of the LiMs. Maintenance of systemic therapy with oral sorafenib, 800 mg/d
2012 July	Multidisciplinary evaluation suggests liver surgery. At preoperative MRI with Gd-EOB-DTPA: 23 LiMs involving all liver segments except S1 (Figure 2A). Liver resection consisting of left lobectomy extended to segment 4a, multiple wedge resections in all the remnant liver segments, except S1 (Figure 2B), and RFTA of 3 LiMs deeply located in S7, S8 and S1-S8, respectively, with uneventful postoperative course. At pathological examination all the resected nodules were metastatic ccRCC, with negative surgical margins
2012 August to 2013 February	Systemic therapy with IFN-α, 9 MU subcutaneously thrice weekly
2013 March	At CECT scan: PaM in the head of the pancreas, measuring 10 mm (Figure 3A), without evidence of further distant metastases. Multidisciplinary evaluation suggests pancreatic resection. Pancreatoduodenectomy (Figure 3B), with postoperative course complicated by pneumonia, treated with antibiotics. At pathological examination: Multiple PaMs of ccRCC, without LyMs and with negative surgical margins
2013, April to November	Maintenance of systemic therapy with IFN-α, 9 MU subcutaneously thrice weekly
2013 November	At CECT scan: Enlarged left mediastinal lymph nodes suggestive of LyMs
2013 December to 2014 November	Systemic therapy with oral sunitinib, 50 mg/d
2014 November	At CECT scan: Progression of mediastinal LyMs up to 40 mm × 36 mm, detection of single LuM, measuring 10 mm, in the superior lobe of the right lung
2014 December	Multidisciplinary evaluation suggests pulmonary resection. Left lower lobectomy and radical mediastinal lymphadenectomy, with uneventful postoperative course. At pathological examination: One nodule of metastatic ccRCC infiltrating the lung parenchyma, measuring 32 mm, without further LyMs, and with negative surgical margins
2015 February	At CECT scan: 2 LuMs, measuring 10 mm each, in the superior lobe of the right lung, single LiM measuring 8 mm in segment S6 (Figure 4A). SBRT of the 2 LuMs
2015 March	Percutaneous RFTA of the LiM in segment S6 (Figure 4B), with uneventful postoperative course
2015 April to 2019 June	No adjuvant systemic therapy. Regular follow-up (Figure 4C). No evidence of recurrence

RCC: Renal cell carcinoma; LyMs: Lymph nodes metastases; CECT: Contrast-enhanced computerized tomography; LuMs: Lung metastasis; CT: Computed tomography; ccRCC: Clear-cell renal cell carcinoma; IMDC: International Metastatic RCC Database Consortium; 5-FU: Fluorouracil; IFN-α: Interferon-alpha; IL-2: Interleukin-2; PaM: Pancreatic metastasis; MRI: Magnetic resonance imaging; Gd-EOB-DTPA: Gadolinium ethoxybenzyl dimeglumine; LiMs: Liver metastases; RFTA: Radiofrequency thermal ablation; SBRT: Stereotactic body radiotherapy.