Treatment of Advanced Renal Cell Carcinoma.pptx

Advanced RCC Surgical approach

1. T reatment of Advanced Renal Cell Carcinoma Dr. Akshay Sarraf 2nd Year Resident Dept. of General surgery

2. Introduction Renal cell carcinomas (RCCs) a re adenocarcinoma arising from the proximal renal tubular epithelium . Accounts for around 90% of renal tumours and constitutes 2–5% of all cancers in adult men and 1–3% in adult women. May be sporadic or familial.  Most commonly associated familial syndrome- von Hippel–Lindau (VHL). 

3. Risk factors- Cigarette smoking, obesity and hypertension. Diuretics, occupational exposure to petrochemicals and dyes and ARCD in patients on long-term haemodialysis .  C linical Presentation- Classic triad of flank pain, haematuria (m/c) and a palpable mass. Constitutional symptoms such as fever, malaise and weight loss in advanced disease.  Bilateral lower limb oedema or recent-onset non-reducing right-sided varicocele 

4. RCC can be classified as: Localized disease  – This includes stage I, II, and III. Advanced disease  – This includes tumor invading beyond Gerota's fascia or extending into the ipsilateral adrenal gland (T4) and metastatic disease (M1). Either of these findings constitutes stage IV RCC.

5. Treatment of Locally Advanced RCC Inferior Vena Cava Involvement Frequent pattern of growth intraluminally into the renal venous circulation. May extend into the IVC with cephalad migration as far as the right atrium or beyond. Involvement of the venous system with RCC occurs in 4% to 10% of patients. 45%-70% of patients with RCC and IVC thrombus can be cured with an aggressive surgical approach, including RN and IVC thrombectomy

6. Suspected in patients with a renal tumor who also have Lower extremity edema, Isolated right-sided varicocele or one that does not collapse with recumbency, Dilated superficial abdominal veins, Proteinuria, Pulmonary embolism, Right atrial mass, or Nonfunction of the involved kidney. Studies confirm tumor thrombus level as an independent predictor of survival and recurrence ( Martinez-Salamanca et al., 2011 ).

7. AJCC TNM staging distinguishes tumors with thrombi above the diaphragm (stage T3c) from those with IVC thrombi below the diaphragm (stage T3b) and those with thrombi only within the renal vein or its major branches (stage T3a). Staging of the level of IVC thrombus: I, adjacent to the ostium of the renal vein; II, extending up to the lower aspect of the liver and below the hepatic veins; III, involving the intrahepatic portion of the IVC but below the diaphragm; and IV, extending above the diaphragm.

8. Patients with level IV IVC thrombi are cured with surgical resection, typically in the absence of metastases and other adverse features Predictor of cancer-specific survival- Microscopic invasion of the wall of the IVC Nodal or metastatic involvement, Tumor grade, Non–clear cell histology, Preoperative anemia, and Body mass index Along with contemporary systemic therapies, overall survival can reach 40% at 5 years ( Dashkevich et al., 2016).

9. MRI, CT, and echocardiography are useful adjuncts in the pre- and perioperative planning settings. MRI is the preferred diagnostic study; CT can provide essentially equivalent information. Imaging should be obtained as close as possible to the date of surgery as progression of the tumor thrombus may mandate important changes in intraoperative management Intraoperative echocardiography can be a valuable adjunct in the operating room to evaluate thrombus extent, monitor embolic phenomenon and cardiac function, and recognize residual tumor during and after resection

10. Treatment Preoperative renal artery embolization is not essential nor recommended; current data suggest an increased risk of major complications and mortality. The surgical approach is tailored to the level of IVC thrombus but uniformly begins with early ligation of the arterial blood supply. Kidney is gently mobilized, leaving it only attached via the renal vein Alternatively addressing IVC thrombus before mobilization of the kidney can be considered and may reduce the risk of tumor embolism.

11. Vascular control for level III and level IV IVC thrombi requires more extensive dissection, venovenous bypass, or cardiopulmonary bypass and hypothermic circulatory arrest. For level III thrombi, mobilization of the liver and exposure of the intrahepatic IVC often allows the thrombus to be mobilized caudad to the hepatic veins. The risk of morbidity can be substantial for thrombi extendin g above the diaphragm, and mortality rates associated with RN and IVC thrombectomy as high as 5% to 10% I n metastatic disease, surgery can impart a significant palliative benefit by preventing pulmonary emboli and minimizing disability from intractable edema, ascites, cardiac dysfunction, or associated local symptoms such as abdominal pain and hematuria.

12. Locally Invasive RCC Locally advanced and invasive (stage T4) RCC are uncommon, accounting for less than 2% of surgical series. Usually experience pain, generally from invasion of the posterior abdominal wall, nerve roots, or paraspinous muscles Large tumors are more likely to metastasize than invade adjacent structures D/D- adrenocortical carcinoma, urothelial carcinoma, sarcoma, and lymphoma

13. Because surgical therapy is the only potentially curative management for RCC, extended operations with en bloc resection of adjacent organs are occasionally indicated. Careful perioperative management is essential including proper bowel preparation, vaccinations for splenectomized patients, and the need for endocrine replacement for patients with bilateral adrenal involvement. However, even with an aggressive surgical approach, the prognosis remains poor.

14. Although negative surgical margins were achieved in 63% of patients in a series, 34 of 38 patients (90%) ultimately died of disease at a median of 12 months after surgery ( Karellas et al., 2009). Incomplete excision of a large primary tumor, or debulking, is rarely indicated because 1-year survival estimates are only 10% to 20%. Radiation therapy has traditionally played little role in the management of locally extensive RCC.

15. Lymph Node Dissection The presence of lymph node metastasis is an important prognostic factor Lymphadenectomy for RCC provides accurate staging; the therapeutic benefits of routine lymphadenectomy are controversial. Only 30% to 43% of clinically enlarged lymph nodes contain metastatic disease. The rates of metastatic nodes a re 20%, 29%, and 90% for nodes 7, 10 and 30 mm in size, respectively (Gershman et al., 2016 ).

16. High-risk features a/w increased risk (greater than 40%) for nodal involvement- (1) Large primary tumor ( > 10 cm); (2) Clinical stage T3/T4; (3) High tumor grade (grade 3/4); (4) Sarcomatoid features; or (5) Histologic tumor necrosis. The EORTC 30881 randomized trial of lymphadenectomy at RN failed to show a survival advantage for most patients undergoing lymphadenectomy

17. Better cancer-specific survival was noted in patients with large, bulky tumors and sarcomatoid features when a more extensive lymph node dissection was performed ( Capitanio et al., 2014). Lymphadenectomy may be performed in patients with clinically suspicious (radiographic or intraoperative) lymphadenopathy for staging purposes. It need not be performed routinely in patients with localized kidney cancer and clinically negative nodes.

18. Neoadjuvant and Adjuvant Therapy Recurrence develops in a significant proportion of patients thought to be rendered disease free after surgical resection. It is primarily because of occult micrometastatic disease. Locally advanced RCC and RCC with other adverse histopathologic features carry a significant risk of recurrence. Distant metastases develop in 20% to 35% and local recurrence in 2% to 5% of patients

19. Randomized trials of adjuvant therapy failed to demonstrate any survival benefit using a variety of agents including IL-2 (Clark et al., 2003), interferon alpha (Messing et al., 2003; Pizzocaro et al., 2001), medroxyprogesterone acetate ( Pizzocaro et al., 1987), and radiation therapy (van der Werf-Messing, 1973). Autologous tumor vaccine–based approaches have also been used to immunize RCC patients in the postoperative setting, again with essentially negative results The emergence of targeted molecular agents and subsequent responses in metastatic disease led to great enthusiasm for new adjuvant trials in high-risk populations. By 2012 six ongoing adjuvant trials were enrolling worldwide, and, as of early 2019, four had been reported

20. In all of these trials patients receiving therapy experienced significantly higher rates of adverse events and there were no differences in overall survival. Given these results, none of the adjuvant studies in this field is convincingly positive, and the standard of care remains observation if the patient will not consider an adjuvant trial Neoadjuvant therapy, with either VEGF-targeted agents or checkpoint inhibitors, represents a new and promising treatment paradigm. Th e potential advantages are tumor cytoreduction and eradication of micrometastatic disease.

21. Emerging data from phase 2 studies using pazopanib, sunitinib, sorafenib, or axitinib indicate average tumor volume reductions of 10% to 31% ( Bindayi et al., 2018). May facilitate tumor resection in patients with imperative indications for nephron-sparing in whom surgery is felt to be unsafe, unfeasible, or not optimized. Six ongoing, early phase neoadjuvant therapy trials are investigating checkpoint inhibitors or other immunomodulatory compounds ( Bindayi et al., 2018).

22. References 1. Bailey & Love’s Short Practice of Surgery, 28 th Edition. 2. Campbell-Walsh-Wein Urology, 12 th Edition. 25

23. THANK YOU 26