Treatment of renal cell carcinoma
Evaluate cTNM staging based on comprehensive imaging findings and initially formulate treatment principles based on cTNM staging. Evaluate the pathological staging based on the invasion range determined by postoperative histology. If there is deviation between pTNM and cTNM staging, revise the postoperative treatment plan according to the pTNM staging results.
(i) Treatment of limited renal cancer
Surgery is the treatment of choice for limited renal cancer. When radical nephrectomy is performed, the addition of regional or expanded lymph node dissection is not recommended (evidence level IIb, recommendation grade A).
1. Radical nephrectomy is the only method that is currently recognized as a possible cure for kidney cancer. Classical radical nephrectomy includes: perinephric fascia, perinephric fat, affected kidney, ipsilateral adrenal gland, hilar lymph nodes and ureter above iliac vessel bifurcation. In modern opinion, if the clinical stage is I or II, the tumor is located in the middle or lower part of the kidney, the tumor is less than 8 cm, and the preoperative CT shows normal adrenal gland, radical nephrectomy with preservation of the ipsilateral adrenal gland can be chosen (evidence level IIIa). However, in this case, if the ipsilateral adrenal gland is found to be abnormal during surgery, the ipsilateral adrenal gland should be removed. Radical nephrectomy can be performed via open surgery or laparoscopic surgery. Open surgery can be performed with either a transabdominal or transumbilical approach, and there is no evidence to suggest which approach is more advantageous. Radical nephrectomy has a mortality rate of approximately 2% [28] and a local recurrence rate of 1% to 2%. Renal artery embolization prior to radical nephrectomy is not recommended (recommendation grade B).
2. nephron sparing surgery (NSS) NSS is recommended for various indications and has the same efficacy as radical nephrectomy (level of evidence IIIa). . NSS can be performed by open surgery or laparoscopic surgery. The local recurrence rate after surgery with preserved renal units is 0-10%, while the local recurrence rate after surgery with tumors ≤4 cm is 0-3%. The risk of potential recurrence after surgery needs to be explained to patients. the mortality rate of NSS is 1~2%.
Indications for NSS: Kidney cancer occurs in patients with anatomical or functional isolated kidney, radical nephrectomy will lead to renal insufficiency or uremia, such as congenital isolated kidney, contralateral renal insufficiency or non-functional person, and bilateral kidney cancer.
Relative indications for NSS: Patients with certain benign diseases in the contralateral kidney of kidney cancer, such as kidney stones, chronic pyelonephritis or other diseases that may lead to deterioration of kidney function (such as hypertension, diabetes, renal artery stenosis, etc.).
The indications and relative indications for NSS are not specifically limited to tumor size.
Indications for NSS can be selected: clinical stage T1a (tumor ≤4cm), tumor located in the periphery of the kidney, single asymptomatic kidney cancer, and normal contralateral kidney function can be selected for NSS (evidence level IIb).
3.Laparoscopic surgery The surgical approaches include laparoscopic radical nephrectomy and laparoscopic partial nephrectomy. The surgical route is divided into transabdominal, retroperitoneal and hand-assisted laparoscopic. The scope and standard of resection are the same as open surgery. Laparoscopic surgery is suitable for patients with limited renal cancer whose tumors are confined to the renal peritoneum, without surrounding tissue invasion and without lymphatic metastasis and venous tumor thrombosis, and its efficacy is comparable to that of open surgery (level of evidence IIIa). However, patients with stage ≥T3 renal cancer, a history of previous kidney surgery, and other non-surgical indications should be considered contraindications to laparoscopic surgery. Laparoscopic surgery also has a certain mortality rate.
4.Minimally invasive treatment Radio-frequency ablation (RFA), high-intensity focused ultrasound (HIFU) and cryoablation are in the clinical research stage, and there is no evidence-based medical grade I-III evidence for the treatment of kidney cancer. They should be selected carefully according to their indications and are not recommended as the first choice of surgical treatment. If such treatment is performed, it should be explained to the patient.
Indications: those who are not suitable for open surgery, those who need to preserve the function of the renal unit as much as possible, those who have contraindications to general anesthesia, those with renal insufficiency, and those who have a requirement for less invasive treatment. Most studies consider it suitable for renal cancer <4cm located in the periphery of the kidney.
5.Renal artery embolization can be used as a palliative treatment for patients who cannot tolerate surgical treatment. Preoperative renal artery embolization may be beneficial in reducing intraoperative bleeding and increasing the chance of radical surgery, but there is no evidence-based level I-III evidence to prove this. Renal artery embolization can cause complications such as puncture site hematoma, post-embolization infarction syndrome, and acute pulmonary infarction. It is not recommended for routine preoperative application.
6.Postoperative adjuvant therapy There is no standard adjuvant therapy plan after surgery for localized renal cancer. pT1a renal cancer has a 5-year survival rate of more than 90% with surgical treatment, and adjuvant therapy is not recommended after surgery. pT1b~pT2 stage renal cancer has metastasis in about 20%~30% of patients within 1-2 years after surgery. Radiotherapy and chemotherapy after surgery cannot reduce the metastasis rate, so the routine application of adjuvant radiotherapy and chemotherapy after surgery is not recommended.
(ii) Treatment of locally progressive renal cancer
The preferred treatment for locally progressive renal cancer is radical nephrectomy, while the metastatic lymph nodes or hemangioma plugs need to be removed or not according to the extent of the lesion. There is no standard treatment plan after surgery. For patients with residual tumor after surgery, immunotherapy or difluorodeoxycytidine (trade name gemcitabine, keyselect) based chemotherapy or (and) radiotherapy are recommended.
Early studies advocated regional or expanded lymph node dissection, while recent findings suggest that regional or expanded lymph node dissection is only practical for determining tumor stage in postoperative lymph node negative patients, while regional or expanded lymph node dissection is only beneficial in a small number of patients with positive lymph nodes, and requires combined immunotherapy or chemotherapy after surgery due to the presence of distant metastases. The combination of immunotherapy or chemotherapy is required after surgery because of the distant metastases.
Most scholars believe that the TNM stage, the length of the tumor embolus, and whether the embolus infiltrates the vena cava wall are directly related to the prognosis [50]. It is recommended that patients with clinical stage T3bN0M0 undergo inferior vena cava tumor embolus removal. This procedure is not recommended for patients with CT or MRI scans suggesting invasion of the inferior vena cava wall or with lymph node metastases or distant metastases. The mortality rate of vena cava aneurysm removal is approximately 9%.
There is no uniform classification of venous aneurysm emboli. The Mayo Clinic’s five-grade classification is recommended: Grade 0: the tumor is confined to the renal vein; Grade I: the tumor invades the inferior vena cava and the tip of the tumor is ≤2 cm from the opening of the renal vein; Grade II: the tumor invades the inferior vena cava below the level of the hepatic vein and the tip of the tumor is >2 cm from the opening of the renal vein; Grade III: the tumor grows to the level of the inferior vena cava in the liver and below the level of the diaphragm Grade IV: tumor embolus invades into the inferior vena cava above the diaphragm.
There is no standard adjuvant treatment plan after radical nephrectomy for locally progressive renal cancer. Kidney cancer is a tumor that is not sensitive to radiation, so radiotherapy alone cannot achieve better results. Preoperative radiotherapy is generally rarely used, and intraoperative or postoperative radiotherapy can be chosen for stage III renal cancer that cannot be completely resected. (The following references have not been modified)
(iii) Treatment of metastatic renal cancer (clinical stage IV)
There is no standard treatment plan for metastatic kidney cancer, and a comprehensive treatment mainly based on internal medicine should be adopted. Surgery is mainly an adjuvant treatment for metastatic kidney cancer, and very few patients can be cured by surgery.
1.Surgical treatment Removal of primary foci in kidney can improve the efficacy of IFN-α or (and) IL-2 in the treatment of metastatic kidney cancer. For patients with isolated metastases after radical nephrectomy and patients with renal cancer with isolated metastases, good behavioral status and low risk factors (see Table II-4), surgical treatment can be chosen. For patients with concomitant metastases, they may be treated simultaneously with renal surgery or in stages depending on the patient’s physical condition. For patients with renal tumor causing severe hematuria, pain and other symptoms, palliative nephrectomy and renal artery embolization can be chosen to relieve symptoms and improve survival quality. The mortality rate of metastatic renal cancer surgery is 2%~11%.
2.Medical treatment The results of randomized controlled study cannot prove that LAK cells, TIL cells and IFN-γ are effective in the treatment of metastatic kidney cancer. At present, IFN-α or (and) IL-2 is the first-line treatment option for metastatic kidney cancer treatment, with an effective rate of about 15%.
Recommended therapeutic dose of IFN-α: IFN-α: 9MIU per dose, im or H, 3 times/week for 12 weeks. The dose can be gradually increased from 3MIU per dose, 3MIU per dose in the first week, 6MIU per dose in the second week, and 9MIU per dose in the third week onwards. blood tests should be performed once a week during treatment, and liver function should be checked once a month. white blood cell count <3×109/L or abnormal liver function should be stopped and treatment should be continued after recovery. If the patient cannot tolerate the dose of 9MIU each time, the dose should be reduced to 6MIU each time or even 3MIU each time.
Commonly used IL-2 regimens abroad.
High-dose regimen: IL-2 6,0~7,2×105IU/[kg(body weight)?8h], intravenously over 15min, days 1 to 5, days 15 to 19. Repeat 1 time after 9 days interval. High-dose application of IL-2 had a 4% mortality rate.
Low-dose regimen I: IL-2 2, 5×105 IU/kg H 5d/W×1
IL-2 1, 25×105IU/kg H 5d /W ×6 every 8 weeks
Low-dose regimen II: 18 MIU/d H 5d/W × 8 weeks
Note: There are no high-dose IL-2 commodities available in China.
The efficacy of commonly used chemotherapeutic agents (either alone or in combination) in metastatic renal cancer cannot yet be determined, and chemotherapy combined with IFN-α or (and) IL-2 has not yet shown an advantage. In recent years, difluorodeoxycytidine based chemotherapy has achieved some efficacy in metastatic renal cancer and may also be used as a first-line treatment option [3].
The results of several randomized controlled clinical studies have shown that multi-targeted kinase inhibitors targeting vascular endothelial growth factor (VEGF) and receptors are effective in the treatment of metastatic kidney cancer in the range of 10% to 40%, with approximately 80% of patients in the treatment group having stable lesions and prolonging the time without disease progression, but the long-term efficacy is still uncertain. However, the long-term efficacy is still uncertain, and long-term maintenance dosing is required. Patients have good tolerance of these drugs, but the treatment is expensive. Multi-targeted kinase inhibitors against VEGF can be used as first-line agents in the treatment of metastatic kidney cancer or as second-line agents after failure of IFN-α or (and) IL-2 therapy.
It is recommended to evaluate the efficacy of immunotherapy or chemotherapy for kidney cancer using the new Rating of Efficacy in Solid Tumors (RECIST).
3.Radiotherapy For patients with local recurrence of tumor bed, regional or distant lymph node metastasis, bone or lung metastasis, palliative radiotherapy can achieve the purpose of pain relief and improvement of survival quality. In recent years, stereotactic radiotherapy, three-dimensional conformal radiotherapy and intensity modulated conformal radiotherapy can play a better control role for recurrent or metastatic lesions.
Sixth, surgical complications
Whether it is open surgery or laparoscopic surgery for kidney cancer, complications such as bleeding, infection, perirenal organ damage (liver, spleen, pancreas, gastrointestinal tract), pleural injury, pulmonary embolism, renal failure, liver failure and urinary leakage may occur, which should be prevented and handled appropriately. Severe cases may lead to patient death due to surgery. Patients and their families should be informed of the risks and possible complications of surgery before surgery.
VII. Prognostic influencing factors
The most important factor affecting the prognosis of kidney cancer is the pathological stage, followed by the histological type. The prognosis of papillary renal cell carcinoma and suspicious cell carcinoma is better than that of clear cell carcinoma; the prognosis of papillary renal cell carcinoma type I is better than that of type II; the prognosis of collecting duct carcinoma is worse than that of clear cell carcinoma [60-62]. In addition, the prognosis of kidney cancer is related to factors such as histological grading, patients’ behavioral status score, symptoms, and the presence of tissue necrosis in the tumor.
VIII. Diagnosis and treatment of hereditary renal cancer
The hereditary renal cancers that have been clearly identified include: (i) VHL syndrome; (ii) hereditary papillary renal cancer; (iii) hereditary smooth muscle tumor disease renal cancer; and (iv) BHD (Birt-Hogg-Dube) syndrome.
(a) Diagnostic points of hereditary renal cancer
(1) The age of disease is mostly middle-aged and young, with/without family history; (2) Renal tumors are often bilateral and multiple, with imaging features of renal cancer; (3) Other manifestations of the above syndromes are present, such as VHL syndrome can be combined with changes of central nervous system and retinal angioblastoma, pancreatic cyst or tumor, adrenal pheochromocytoma, epididymal papillary cystadenoma, renal cyst, etc.; (4) Testing confirms the corresponding chromosomal and genetic abnormalities.
(ii) Treatment of hereditary renal cancer
VHL syndrome is more frequently reported, while other types of hereditary renal cancer are only reported in individual cases or small samples. Most hereditary renal cancers have similar treatment methods and principles to those of VHL syndrome.
Treatment principles of renal cancer with VHL syndrome: observe and wait for renal tumor diameter <3cm, and consider surgery when the maximum tumor diameter is ≥3cm, with NSS as the first choice, including tumor enucleation.