Kidney cancer accounts for about 3% of human malignancies and ranks among the top 10 malignancies in developed countries. 2008, there were about 271,000 new cases of kidney cancer worldwide, ranking 13th in malignancies, and 116,000 deaths due to kidney cancer. 20-30% of kidney cancers have distant metastases at the time of initial diagnosis, and 20% of patients have recurrence or metastases at postoperative follow-up. The prognosis of metastatic kidney cancer is very poor and has become a major health problem of oncology worldwide.
The incidence of kidney cancer in China is also on the rise year by year, and the high incidence age is 50-70 years old. The incidence rate of kidney cancer in China has increased from 2.68 cases/100,000 people in 1988 to 4.17 cases/100,000 people in 2002 for men and from 1.58 cases/100,000 people to 2.46 cases/100,000 people for women. In Shanghai, for example, the incidence rate of kidney cancer showed an obvious trend of rapid growth, with the incidence rate of men rising from 1.50 cases/100,000 in 1983 to 14.75 cases/100,000 in 2009, an increase of 8.8 times in 26 years, with an average annual growth rate of more than 9%. The incidence rate of kidney cancer in China also has obvious geographical distribution differences.
The National Cancer Prevention and Treatment Research Office and the Health Statistics Information Center of the Ministry of Health conducted a statistical analysis of kidney cancer patients in 11 registries with complete data from 1988 to 2002, and found that the incidence rate and death rate of kidney cancer varied greatly among regions, with a maximum difference of 43 times, and urban areas were higher than rural areas.
In 2002, the highest incidence rate of male kidney cancer in Hangzhou, Beijing and Shanghai was above 8,0/100,000, while the lowest incidence rate in Fusui, Guangxi was only 0,2/100,000, a difference of 40 times; the incidence rate of female kidney cancer in Beijing, Shanghai, Hangzhou, Dalian and Tianjin was over 3,6/100,000, while the lowest incidence rate was only 0,1/100,000, a difference of 36 times. During the same period, the highest death rate of kidney cancer in men was in Tianjin, Shanghai, Dalian and Beijing, which exceeded 2.6 per 100,000; the death rate of kidney cancer in women was over 1.9 per 100,000. The current situation and development trend of kidney cancer diagnosis and treatment in China are reviewed.
I. Current situation and new technology of kidney cancer diagnosis
With the technological innovation of imaging examination, more and more new imaging diagnostic techniques are applied in clinical practice, which, together with the enhancement of public awareness of medical examination, has led to an increase in the detection rate of clinical asymptomatic kidney cancer. Li Ming et al. summarized and analyzed the data of 1975 new kidney cancer cases in 23 hospitals in Beijing, Shanghai and Tianjin from August 2007 to October 2008, among which 1238 cases (62.7%) were detected by asymptomatic physical examination.
Among the 1975 cases, 1,806 cases underwent CT examination, 1,775 cases underwent B-ultrasound examination, 1,296 cases underwent chest X-ray examination, 453 cases underwent IVU examination, 304 cases underwent MRI examination, 88 cases underwent nuclear bone scan, and 19 cases underwent PET-CT examination, and renal CT and B-ultrasound have become the most common auxiliary examination methods for diagnosing kidney cancer in China.
The changes in the methods of kidney cancer diagnosis and efficacy observation mainly include.
①The wide application of B-ultrasound, especially the popularization of B-ultrasound physical examination, has led to the detection of more and more asymptomatic incidental carcinomas and small renal carcinomas (maximum diameter <4 cm).
②Planar + enhanced CT scan has become the standard imaging method for clinical diagnosis and staging of kidney cancer.
(iii) IVU is no longer required for renal tumors. CT-enhanced scan can also evaluate the contralateral renal function, and nuclear nephrography can evaluate the renal function of the affected side and the contralateral side, and CTU and MRU can also replace IVU for urinary tract evaluation.
④Renal arteriography, as an invasive test, has been replaced by other non-invasive imaging methods that are less invasive and have a higher diagnostic yield, such as ultrasonography, spiral CT renal arteriography 3D image reconstruction, and MRI.
⑤ MRI is more widely used, and enhanced scans, diffusion-weighted, and pressurized lipid signals are useful for the differential diagnosis of small renal cancer and the assessment of efficacy in the short term after cryoablation.
⑥Ultrasonography has higher diagnostic sensitivity and specificity than enhanced CT for small renal cancer, and there is no ionizing radiation. It can sensitively and effectively reflect the blood supply of cystic renal lesions, and has become an important method for diagnosing cystic renal cancer, and can also be used as a follow-up for complex cystic renal lesions; it can be applied to predict the efficacy after radiofrequency ablation or cryotherapy.
(7) PET-CT in renal cancer is not yet mature. 18F-FDG is currently the most commonly used PET imaging agent, but the literature reports that renal clear cell carcinoma is less likely to take up 18F-FDG; PET with llC-acetate imaging has gradually been put into clinical use, which can make up for the shortage of 18F-FDG. (8) Renal tumor puncture biopsy can be used for pathological diagnosis before neoadjuvant therapy, as well as for treatment decision of small renal cancer.
In recent years, with the development of imaging, minimally invasive procedures such as freezing and radiofrequency ablation have replaced part of the nephrectomy surgery for renal cancer, and puncture biopsy of renal masses has also received increasing attention. However, the use of puncture biopsy for the diagnosis of renal masses is still controversial, and most physicians believe that puncture biopsy cannot significantly improve the diagnosis rate and influence the choice of treatment plan.
The 2013 edition of the European Society of Urology guidelines for the diagnosis and management of renal cancer includes the following indications for renal puncture biopsy: (1) renal occurrences with an unclear diagnosis on imaging; (2) selection of small renal cancers suitable for observation and follow-up; (3) obtaining a definitive pathologic diagnosis before ablative therapy; and (4) obtaining a definitive pathologic diagnosis before ablative therapy. (3) to obtain a definite pathological diagnosis before ablation therapy: (4) to select the most appropriate targeted therapy for patients with metastatic kidney cancer. The main objectives of kidney tumor aspiration diagnosis are: (1) to clarify the benign and malignant nature of kidney tumor; (2) to clarify the pathological type; and (3) to clarify the cell grading.
II. Changes of surgical treatment for early stage kidney cancer
Although the surgical treatment of kidney cancer is still based on open surgery and standard treatment, however, with the continuous improvement of domestic clinical imaging, surgical instruments and surgical techniques, the following development trends have emerged.
(A) Trend from open surgery to lumpectomy
Laparoscopic surgery is fully developed: According to the data of l975 new kidney cancer patients in 23 hospitals nationwide reported by Li Ming et al, laparoscopic surgery accounted for 19.0% (351 cases) of the l844 surgically treated patients. laparoscopic surgery accounted for 26.2% of all surgically treated kidney cancer patients reported by Shanghai Renji Hospital in 2012. In some units where laparoscopic surgery is the main procedure, this percentage even exceeds 80%.
In China, scholars are more familiar with retroperitoneal anatomy, and the retroperitoneal route is the most common surgical approach. Most scholars believe that Hem-o-lok ligature clamps are convenient, effective, safe, and affordable in the management of renal arteries during retroperitoneoscopic nephrectomy, and should be the standard method for the management of renal arteries during retroperitoneoscopic nephrectomy.
In addition, some units in China have also tried to perform posterior laparoscopic radical surgery combined with venous cancer thrombus removal for stage T3 renal cancer with renal vein and/or inferior vena cava cancer thrombus. Lv Wencheng et al. used the posterior laparoscopic approach to perform radical nephrectomy in 7 patients with left kidney cancer with renal vein thrombosis, and concluded that radical resection of left kidney cancer with renal vein thrombosis by the posterior laparoscopic approach was safe and feasible.
2.Modified application of single-port laparoscopy: In 2007, Rane et al. first reported R-port single-port laparoscopic surgery, and in 2008, Sun Yinghao et al. completed the first single-port laparoscopic nephrectomy for non-functional nephrectomy in China. Since then, single-port laparoscopic techniques have received widespread attention from scholars at home and abroad.
The current stage of single-port laparoscopic kidney cancer surgery in domestic urology has the following innovations and improvements.
①Homemade single-hole multi-channel device. Due to the high price of commercial single-hole multi-channel devices, domestic operators have independently developed a variety of homemade single-hole multi-channel devices, which is one of the important reasons why single-hole laparoscopic surgery can be rapidly popularized in China. At present, the proportion of radical nephrectomies performed with homemade devices in China is about 56,2%.
②Optimize the location of the surgical incision and improve the exposure of the operative field. Although the umbilical hole is the best location for single-port laparoscopic surgical incision selection, the distance and small angle between the umbilical hole and the kidney greatly increase the difficulty and risk of surgery, and most domestic urologists are more familiar with the access and anatomical features of posterior laparoscopic surgery, so the incision can be moved to the level of the anterior superior iliac spine under the affected rib margin or mid-axillary line.
Although single-port laparoscopic techniques have been initially applied in kidney cancer surgery, they are still mainly used for non-complex surgeries due to insufficient technical experience and lack of instruments and equipment. Robot-assisted laparoscopic technology has greatly improved the safety and clinical efficacy of complex surgery with its flexible intracavitary operation and high-definition three-dimensional field of view, and is considered to be the development direction of single-port laparoscopic surgery.
In 2009, Xu A-Xiang reported 6 cases of da Vinci robot-assisted laparoscopic renal unit preservation surgery, among which 1 case was converted to open surgery and 5 cases were successfully operated robotically, with an average operation time (excluding preoperative robot preparation time) of 130 min and renal artery blocking time of 40 min. intraoperative bleeding volume of 188 ml. As of June 30, 2013, the installed base of da Vinci robotic surgery system was 16 units in China, 8 units in Hong Kong, and 14 units in Taiwan. It is believed that in the near future, more and more robotic devices will be available in China, and robotic surgery in kidney cancer will be better promoted.
(2) The trend from radical nephrectomy to kidney unit preserving surgery
1. The proportion of kidney unit preserving surgery is obviously increasing: postoperative renal insufficiency of kidney cancer patients will affect their survival. With the increasing clinical emphasis on the protection of renal function, renal unit preserving surgery has changed from absolute indications (isolated kidney, contralateral renal insufficiency or non-functioning, bilateral renal cancer, etc.) to relative and selective indications, and is applied to more and more patients, and renal tumors of stage T1b or even stage T2a may undergo renal unit preserving surgery. According to the data of kidney cancer patients from 23 hospitals nationwide reported in 2010, renal unit preserving surgery accounted for 17,6% of all kidney cancer cases.
In 2012, Shanghai Renji Hospital reported that the proportion of kidney unit-preserving surgery had increased to 34.7%. However, there is still a gap between this rate and some large medical centers abroad. A European multicenter study showed that from 1987 to 2007, the proportion of kidney unit preserving surgery increased from 11.0% to 50.1%; data from Memorial Sloan Kettering Cancer Center (MSKCC) showed that from 2000 to 2007, the proportion of kidney preserving surgery for stage T1a tumors increased from 69% to 89%, and the proportion of kidney preserving surgery for stage T1b tumors increased from 20% to 60%. The proportion of kidney unit preservation surgery in China still has much room for increase.
Some new adjuvant devices have also facilitated the development of renal unit-preserving surgery. For example, the use of bidirectional barbed sutures in posterior laparoscopic partial nephrectomy can effectively shorten the suturing time and thermal ischemia time, which is also helpful for preserving renal function.
2. More comprehensive clinical and imaging evaluation systems: P.A.U.D.A scoring system, R,E,N.A,L scoring system and C-index tumor localization are the most commonly used evaluation methods for preserving renal units preoperatively. Zhang Dongxu et al. retrospectively analyzed the value of posterior laparoscopic partial nephrectomy in 79 patients with P, A, U, D, and A scores of intermediate risk for early renal cancer.
The preoperative P, A, U, D, A scores were all in the intermediate-risk group, among which 13 cases had tumor invasion of the collecting system, 5 cases had involvement of the renal sinus, and 10 cases were near the hilar vessels on imaging. There were 3 cases of postoperative leakage and 7 cases of transient increase in serum creatinine, all of which decreased to normal range within 6 weeks. At 10-84 months postoperative follow-up, the glomerular filtration rate (GFR) of 77 patients was not statistically significant at 6 months postoperatively compared with that before surgery, while the GFR of the other 2 patients decreased by 30% and 35%, respectively; no tumor recurrence or metastasis was observed in any of the patients.
This suggests that retroperitoneoscopic partial nephrectomy is relatively safe and feasible in patients with P, A, U, D, and A scores of intermediate risk for early-stage renal cancer. In addition, Wang et al. performed external validation of the R, E, N, A, L scoring system for predicting tumor grade of kidney cancer using clinical data of Chinese kidney cancer patients. 45.5% of 391 kidney cancer patients were pathologically diagnosed with high-grade tumors, and the area under the AUC curve of the column line plot of the R, E, N, A, L scoring system was 0.73. It is highly accurate for predicting high-grade kidney cancer and has some guidance for the prognosis of kidney cancer patients. It also has a certain guiding significance for the prognosis of kidney cancer patients.
The CT angiography of renal artery can determine the number of renal artery branches and the presence of ectopic renal artery before operation, which makes the operation of preserved renal unit safer and more effective, and also provides the basis for super-selective renal artery branch blocking technique.
3. new vascular blocking techniques and concepts: ① super-selective blocking of renal artery branches (renal segmental vessels). shao et al. established a laparoscopic partial nephrectomy method with preoperative 3D CT reconstruction of super-selective blocking of renal artery branches. 82 cases of stage T1a/T1b renal cancer were retrospectively analyzed. median operation time was 90 min, median blocking time was 24 min, and median bleeding volume was 200 ml.
Six patients required blood transfusion, five had postoperative hematuria that improved after conservative observation, and one had postoperative hematoma with selective renal artery embolization. All cases had complete tumor resection with no positive margins, and no recurrence of metastasis was observed at a median follow-up of 20 months. This technique has been relatively systematic and mature, enabling patients to preserve more renal function postoperatively, and deserves further promotion in units skilled in laparoscopic surgery.
②The concept of zero ischemia. Zhao et al. reported 42 cases of renal unit preservation surgery with the aid of radiofrequency ablation without blocking the renal vasculature. The tumor-specific survival rate at 3 years was 100% and the recurrence-free survival rate at 3 years was 96%. This indicates that radiofrequency ablation-assisted zero ischemia renal unit preservation surgery is feasible, and although the incidence of urinary leakage may be slightly higher, it has a definite value for preserving the renal function of patients.
4. Intraoperative ultrasound localization for renal unit preservation surgery: The main roles of intraoperative ultrasound application for renal tumor are: ① intraoperative tumor localization: ② check the blood supply of tumor tissue and postoperative renal trauma bleeding: ③ probe the satellite foci around the target tumor to ensure the completeness of resection.
Wu Jiangtao et al. used Aloka 4000 color ultrasound diagnostic instrument and laparoscopic ultrasound probe to perform intraoperative ultrasound localization in 5 cases. The tumors were 0.8-1.5 cm in diameter and were confined to the renal parenchyma. Therefore, intraoperative ultrasound is necessary for accurate localization. The surgeon can accurately locate the microscopic kidney cancer buried below the renal cortex and completely remove the tumor, while effectively reducing intraoperative and postoperative bleeding and improving surgical safety.
(III) Trend from single surgical treatment to multidisciplinary comprehensive treatment
1. Postoperative adjuvant therapy for limited high-risk recurrent/metastatic kidney cancer: the application of targeted therapy has filled the gap of drug therapy for advanced kidney cancer, but there are few reports on postoperative adjuvant drug therapy for kidney cancer, and several international studies are in progress. In China, Zhao et al. retrospectively analyzed 43 high-risk recurrent/metastatic limited renal cancers that received adjuvant treatment with sunitinib (23 cases) or sorafenib (20 cases) for 1 year after radical surgery and compared them with 388 high-risk limited renal cancers that did not receive postoperative adjuvant drug therapy in the same center.
The postoperative tumor recurrence rates were 17,4% and 15,0% in the sunitinib and sorafenib groups, respectively, which were lower than the 38,7% in the no-treatment group. The disease-free survival time was (16,9±6,1) months in the sunitinib group and (18,9±5,9) months in the sorafenib group, both longer than the (13,3±7,2) months in the no-treatment group. Although the number of cases in this study was small and it was a retrospective historical controlled study, the results still have some clinical reference value and provide a basis for subsequent randomized controlled studies with larger samples.
At present, the adjuvant clinical trials for postoperative renal cancer in China include sorafenib, sunitinib, pazopanib and axitinib, the results of which are worthy of expectation and are expected to change the existing adjuvant treatment model for postoperative renal cancer.
Pre-operative neoadjuvant therapy: Pre-operative neoadjuvant targeted drug therapy for kidney cancer is less reported. Preliminary studies found that targeted drugs have limited efficacy in shrinking the primary tumor of kidney, and the adverse effects may affect the subsequent surgical treatment and increase the incidence of perioperative complications. Ju et al. Zhao reported 2 patients with renal cancer who underwent radical nephrectomy after sunitinib treatment, one of whom had combined retroperitoneal lymph node enlargement and one had combined adrenal metastasis, both of whom were free of recurrent metastases at postoperative follow-up.
However, based on available clinical observations, the patients most likely to benefit from preoperative adjuvant targeted therapy are those whose tumors shrank significantly after treatment, including primary renal tumors, regional metastatic lymph nodes, and renal vein or inferior vena cava tumor emboli, allowing patients who were previously inoperable for surgical resection the opportunity for new radical surgery, or even surgery to preserve the renal unit. Li Chunxiang et al. reported a case of locally advanced central renal cancer in the left isolated kidney after receiving neoadjuvant treatment with sunitinib, which resulted in more significant tumor shrinkage and improved relationship between the tumor and the colonic and renal hilum vessels, thus gaining the opportunity to preserve the renal unit for surgery.
(iv) Attempts of other treatment alternatives to surgery
Compared with surgical resection of kidney cancer, minimally invasive ablation methods can denature and necrosis the tumor by acting directly on it in situ, and the main methods include cryoablation, radiofrequency ablation, high-intensity focused ultrasound, laser thermal ablation, microwave thermal ablation, radiosurgery radio-wave knife and so on. Many patients who cannot tolerate surgical treatment can control renal tumor by these alternative treatments.
Currently, many centers in China are carrying out cryoablation or radiofrequency ablation treatment for renal tumors, but there are not many reports in the domestic related literature, and the main operation routes are open, laparoscopic and percutaneous.
Lien Huibo et al. conducted a preliminary comparison of the clinical efficacy of laparoscopic cold circulation radiofrequency ablation and partial nephrectomy for the treatment of limited renal cancer, and the operative time was (87±22) and (146+45) min, the intraoperative bleeding was (46±27) and (274±269) ml, and the postoperative hospital stay was (5±1) and (10+2) d, respectively. The differences between the groups were statistically significant (P<0, 01), suggesting that laparoscopic cold-circulation radiofrequency ablation was safe and effective in the treatment of renal cancer, and was superior to laparoscopic partial nephrectomy in terms of operative time, intraoperative bleeding and postoperative recovery. < p="">
In terms of renal tumor control, the 3-year recurrence rate was 2,5%, and the 3-year overall survival rate and tumor-related survival rate were both 100%. Xu Bin et al. reported the first transumbilical single-port laparoscopic cryoablation of renal tumors in China. For patients with early stage renal cancer who cannot tolerate surgery due to combined systemic diseases, percutaneous ablation under local anesthesia can be chosen. The average tumor size was 2,9 cm (1,4-4,8 cm), and the average operation time was 68 min. There were no complications such as bleeding, perirenal hematoma, granulomatous hematuria, urinary leakage and skin frostbite, and no local recurrence, puncture channel implantation or distant metastasis were observed during the follow-up period.
C. Treatment of advanced kidney cancer enters the era of targeted therapy
In 2012, the first-line treatment for patients with advanced kidney cancer in China was as follows: about 1500 patients received sorafenib, about 1200 patients received sunitinib, about 500 patients participated in clinical trials of new drugs, and the rest received immunotherapy, traditional Chinese medicine, best supportive care or observation. The remaining patients received immunotherapy, TCM, best supportive care or observation.
The overall efficacy of targeted drug therapy for patients with advanced kidney cancer in China appears to be better than that of patients with advanced kidney cancer in Western countries, with the median PFS of sunitinib, sorafenib and everolimus being longer than that reported in foreign studies, for reasons that have not been clarified. In addition, there are a number of new class I drugs undergoing phase I-II clinical trials in China. Famitinib is a multi-targeted tyrosine kinase inhibitor developed independently in China. Preliminary studies have shown that the anti-tumor effects of famitinib are stronger than those of sunitinib in vivo and in vitro. Several oncology centers in China are conducting a phase II clinical trial of famitinib and sunitinib for the randomized controlled treatment of advanced kidney cancer, and the study is about to be completed.
Another drug that will soon begin a phase II clinical trial (also with sunitinib as a control) is anlotinib, also a multi-target tyrosine kinase inhibitor. It is believed that domestic targeted drugs for kidney cancer will soon be available in China, which will hopefully bring more optimal treatment for patients with advanced kidney cancer.