Professor Ye Dingwei: From science popularization to academic frontier, this article summarizes the most comprehensive knowledge of kidney cancer

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The theme of this year’s World Kidney Day is: Kidney health for everyone around the world-for everyone, everywhere, from prevention to diagnosis and treatment.Renal cancer is the third most common malignant tumor in the urinary system, but its mortality rate ranks ahead of prostate and bladder cancer, ranking first among the three major malignant tumors in the urinary system.Renal cancer is the third most common malignant tumor in the urinary system, but its mortality rate is the highest among the three common tumors in the urinary system.The public is far less aware of kidney cancer knowledge than prostate and bladder cancer.Moreover, the incidence of kidney cancer in China has been increasing year by year.According to the latest cancer statistics in 2018, the annual growth rate of kidney cancer incidence in China has exceeded 7%, and this value was only 3% 10 years ago.The medical community invited Prof. Ye Dingwei, the Deputy Secretary of the Party Committee of the Affiliated Tumor Hospital of Fudan University and Professor of Urology, to comprehensively introduce the knowledge of kidney cancer from the perspective of popular science and professional frontiers.Kidney Cancer Screening Prevention? Are there guidelines for screening for kidney cancer?There is no uniform screening guideline for kidney cancer.? Who needs to be screened early?The incidence of kidney cancer is not high. It is only one-fifth of lung cancer. There are not many kidney cancers that can be found through large-scale screening. For example, if you screen 100,000 ordinary people, you can find less than 10 kidney tumors.Therefore, the main focus of screening is on high-risk kidney cancer populations, also known as “target populations”, including: patients with VHL or other familial renal cancer syndromes and their immediate family members; patients with end-stage renal failure are usuallyIt is accompanied by a cyst (liquid cavity in the kidney), of which 1% of patients will eventually develop kidney cancer; in patients with tuberous sclerosis, this is a syndrome that causes benign skin damage and brain blood vesselsDamage and causes epilepsy or mental retardation, benign angiopathy of the kidneys (angiomyolipoma), and kidney cancer.These patients should have regular ultrasound and CT examinations every year to ensure their health and high quality of life.Is kidney cancer genetically related?Hereditary kidney cancers are also considered familial kidney cancers because they spread throughout the family.In fact, only 3% to 4% of kidney cancers are familial, and the remaining kidney cancers are considered sporadic.Sporadication refers to patients who do not have a family history of kidney cancer, and their cancer has developed and grown in an unpredictable manner.The investigation found that some kidney cancers have a family tendency, for example, both brothers have kidney cancer, or 3 to 5 people in a family have kidney cancer.Certain hereditary diseases such as tuberous sclerosis and multiple neurofibromatosis can be associated with renal cell carcinoma; there are familial renal cancers of the retinal hemangioma, which can be multifocal cancers or intracystic cancers, and VHL gene mutations are also the cause of renal cancerOne of the reasons.? Can supplements, etc. prevent kidney cancer?The market for health supplements is mixed, and supplementary supplements must not blindly follow the trend and maintain good eating habits. The majority of people’s daily intake of nutrients is sufficient. It is not necessary to supplement supplements too much to avoid excessive nutrition or other problems.20% and 30% of kidney cancers are attributed to tobacco and obesity, respectively.High-fat and high-protein diets can also increase the risk of kidney cancer. Conversely, a high intake of fruits and vegetables can reduce this risk.No research has confirmed that daily intake of vitamins can reduce the risk of kidney cancer, so we don’t know if vitamins can prevent it.Although the incidence of kidney cancer in the general population can be reduced through a healthy lifestyle, the vast majority of sporadic kidney cancer is still inevitable, which is an inevitable result of aging population.Kidney cancer diagnosis? Are the kidneys found to be kidney cancer?Renal tumors are classified into benign and malignant.Benign tumors include: renal angiomyolipoma (hamsteroma), renal cortical adenoma, juxtaglomerular cell tumor, fibroma, leiomyoma, etc .; malignant tumors include: renal cell carcinoma and renal pelvis derived from epithelial tissueUrinary epithelial cancer; fibrosarcoma, liposarcoma, leiomyosarcoma, rhabdomyosarcoma derived from mesenchymal tissue; nephroblastoma and embryonic cancer derived from embryonic tissue.A large amount of data show that renal malignant tumors account for 96% to 98% of all renal tumors, of which renal cancer is the main type, accounting for about 90%, and the remaining 10% are most common in renal pelvic cancer.Some benign tumors are difficult to distinguish from malignant tumors and require an experienced oncologist to diagnose and treat them.What are the common symptoms of kidney cancer?The classic “triple sign” of classic kidney cancer: hematuria, abdominal pain, and abdominal mass. Only 6% to 7% of patients will appear.Other symptoms (systemic manifestations): Common symptoms of malignant tumors such as weight loss, fever, night sweats, decreased appetite, fatigue, edema of the lower limbs.Symptoms caused by cancer metastasis, such as chronic cough caused by lung metastasis, bone pain caused by bone metastasis, and jaundice caused by liver metastasis.Paracancerous syndrome: literally, the protein produced and secreted by kidney cancer enters the blood to cause possible symptoms: hypercalcemia, polycythemia, hypertension, impaired liver function without liver metastasis (Stauffer syndrome).Renal cancer has no obvious clinical symptoms in the early stage. Most of the above symptoms and signs indicate that renal cancer has developed more seriously, and the treatment is relatively more complicated.How to diagnose kidney cancer early?Kidney cancer patients often have such questions: Can their tumors be detected early?For specific tumors, doctors can detect and diagnose them early through specific screening methods, and kidney cancer is no exception.An ideal screening test needs to meet the conditions: simple, economical, highly accurate, and widely available.Ultrasound can detect early-stage renal tumors. It has the advantages of non-invasiveness, low price, and high accuracy. It is currently the most important method for screening. Ultrasound can even find small tumors with a diameter of 1 cm.More than 70% of kidney cancers detected by routine physical examination imaging are early and can be cured by surgery.At the current medical level, I recommend that visceral ultrasonography be performed at least once a year, which is conducive to early detection of tumors of the kidney and other organs, which is economical and convenient without pain.Kidney Cancer Treatment? What are the common treatments for kidney cancer?Based on the pathological stage of renal cancer and the overall physical condition of the patient, one or more treatment methods can be considered for single or combined treatment: surgery; molecular targeted therapy for immunotherapy; radiotherapy, energy ablation therapy, etc.? Can kidney cancer patients undergo surgery?Surgery is the fundamental method for the treatment of kidney cancer.Especially for patients with localized disease, surgery can cure most patients and make them long-term survival.For locally advanced patients, a combination of multiple forms of treatment is often required. In addition to surgery, systemic treatment is required to reduce the risk of recurrence.For patients with advanced renal cell carcinoma who have metastasized distantly or who have completely lost the chance of surgery, they should be treated with systemic therapy in combination with as much as possible after renal tumor resection.Radiotherapy can alleviate the symptoms caused by local compression of normal tissues by tumors.? Is chemotherapy necessary after surgery?Doesn’t chemotherapy mean no relapse?Renal cancer is not sensitive to chemotherapy and is inherently resistant to chemotherapy drugs.Almost all chemotherapy drugs have been used to treat kidney cancer, but none have been particularly effective.The only ones with more than 10% efficiency were 5-fluorouracil, gemcitabine, and doxorubicin.After the operation, the doctor will give you some advice on the recurrence of the tumor.Even very early kidney cancer cannot rule out the possibility of tumor recurrence.Through the scale and formula, the doctor will evaluate the recurrence risk of each patient after surgery. If it is at a medium to high risk, the chance of recurrence is relatively high, and adjuvant treatment may be needed.Prophylactic treatment, usually to reduce the chance of recurrence after radical surgery, can be called adjuvant therapy.Adjuvant therapies for clinical applications include cytokine therapy, targeted therapy, and new immunotherapy.? Postoperative pathological report shows some lymph node metastasis, is it not cut?Local lymph node metastasis is a locally advanced case. The so-called locally advanced mainly refers to the fact that distant metastasis has not occurred, but the primary tumor has developed locally and has invaded the peripheral kidney fat, lymph nodes, large veins and adjacent organs.The first task for these patients is to safely remove all visible tumors.For example, if the patient has lymph node metastasis, all metastatic lymph nodes should be removed as much as possible under the premise of safety.Patients with locally advanced disease are most worried about tumor recurrence. The recurrence rate in the middle-risk group is 20% within 5 years, while the recurrence rate in the high-risk group is as high as 70%.• Does recurrence mean no cure after surgery?Will it still recur?The local recurrence of the kidney is relatively limited and can be completely resected or can reach the level of radical cure. If the local lesion is very extensive and cannot be completely resected or one or more metastases already exist in other organs / sites far from the kidney, the surgery has not reached the radicalthe goal of.Many patients have difficulty accepting recurrence and metastasis after surgery. They believe that no metastasis was found in the preoperative imaging examination, and the tumor was completely removed after surgery.The reason is that renal cancer cells may have been latent to other organs of the body along with blood flow and lymphatic system before surgery.After months or years, these unseen cancer cells grow and cause disease recurrence, which is called “micrometastasis.”Micrometastasis is one of the main causes of tumor recurrence.The most common metastatic site of kidney cancer is the lung. Others include liver, lymph nodes, adrenal glands, bones, and brain. Therefore, routine review of the lungs and abdomen is important.The micrometastasis cannot be detected by naked eye, surgical exploration and imaging examination, which makes the evaluation of micrometastasis difficult and can only be followed closely after surgery.Renal cancer recurrence may occur decades after surgery, but most of them occur within 1 to 3 years. Therefore, the doctor will initially arrange a more rigorous follow-up and gradually extend it later.There is no recurrence after more than 5 years of follow-up, the risk of recurrence is lower, but it does not drop to zero, and still cannot be taken lightly.How do kidney cancer patients eat healthier?Rehabilitation and maintenance of kidney cancer after surgery is also very important. If performed properly, it can effectively improve the patient’s physical fitness and immunity, which is of great significance for preventing tumor recurrence.At the same time, renal cancer patients need to protect renal function after surgery.Food diversity: Eat a variety of vegetables, fruits and rough processed staple foods, mainly plant foods.Maintain a proper weight and avoid being underweight or overweight.Maintain proper physical activity and actively participate in appropriate physical activities.Quit smoking strictly and it is recommended not to drink alcohol.The daily intake of red meat (referring to beef, lamb, pork and its products) is below 80g. Choose poultry and fish as much as possible; reduce the intake of soy products (tofu, etc.).Limit animal fat intake and choose limited amounts of vegetable oils. Total fat and oil supply account for 15% to 30% of total energy.The diet should be light and not salty. Do not use more than 6g of salt daily; and limit sugar intake.Do not eat moldy and spoiled food.When cooking fish and meat, don’t make it too hot, don’t eat charred food, don’t eat grilled meat and pickled food.For food additives, pesticides and their residues, and other chemical pollutants, monitor their safety limits.Avoid using nephrotoxic drugs: such as non-steroidal anti-inflammatory drugs, certain antibiotics, etc.Actively monitor and control blood pressure in the normal range; control blood sugar is normal.Advanced version: Academic Article 1 Renal cancer is a malignant tumor with a genetic tendency. In the past, we thought that the incidence of hereditary kidney cancer was between 3% and 5%.However, with the development of genetic testing technology and new understanding of hereditary diseases, the incidence of hereditary kidney cancer is likely to be underestimated.Second-generation sequencing technology (NGS) has gradually become an important part in the diagnosis and treatment of urinary system tumors, and its scope includes all aspects of diagnosis, prognosis, treatment and genetic counseling.Can genetic testing find more genetic diseases?Does genetic testing change patients’ follow-up treatment?Most renal cell carcinomas are sporadic, but 5% to 8% of renal cell carcinomas have a family genetic background.In young patients, more than 10% of kidney cancers have a familial genetic background.Some of these patients with hereditary kidney cancer have the typical clinical manifestations of hereditary syndromes, and the clinical manifestations of other patients are atypical or ambiguous or even unknown.The proportion of hereditary kidney cancers without extrarenal syndrome is <20%, but they also often have related genetic mutations and can only be diagnosed by genetic testing.A recent document suggested that CDKN2B mutations are present in 5% of patients with hereditary renal cancer without extrarenal syndrome.Such findings suggest that more hereditary kidney cancers may be ignored due to the absence of typical extrarenal manifestations, and hereditary renal cancers may not be limited to now known hereditary kidney tumors.Before the rise of second-generation gene sequencing technology, doctors mainly performed genetic screening through clear family history or clinical manifestations, so the proportion of hereditary kidney cancer in all kidney cancers may be underestimated.Through genetic testing, we may be able to discover more potential genetic diseases and even new genetically related mutant genes.In immunotherapy, some indicators such as tumor mutation load (TMB) and microsatellite instability (MSI) may have some predictive significance.Some studies have suggested that the PBRM1 gene can be used as a biomarker for the efficacy of immunotherapy for renal cancer, and has a certain suggestion.FH gene mutation-related kidney cancer and XP11.2-related kidney cancer have high malignancy, and rapid progress requires faster and stronger intervention by doctors. These gene mutation-related kidney cancer treatment methods are different.The results of genetic testing for renal cancer targeted therapies have emerged endlessly, but few major discoveries have been made.BRCA1 / 2 mutations are relatively rare in kidney cancer, but if such mutations are found, it suggests that PARP inhibitors may have a certain effect.And more biomarkers are being explored.2 Receptor tyrosine kinase inhibitors and mTOR inhibitors bring hope for systemic treatment of advanced renal cancer. What are the current clinical protocols?What research progress?Since 2005, the US FDA approved sorafenib for first-line treatment of advanced kidney cancer, and dozens of targeted drugs have been approved for first-line or sequential treatment of advanced kidney cancer, mainly divided into two categories, Namely receptor tyrosine kinase inhibitors and mTOR inhibitors.For the treatment of advanced renal cancer, the most important thing is to stratify and treat. Whether it is the MSKCC scoring system developed in early 2002 or the IMDC scoring system established in 2009 based on the International Metastatic Renal Cell Carcinoma Database, it willCancer stratified into three groups of low, middle and high risk.These two prognostic models have been validated by a large number of research data. At present, IMDC scores are more widely used in the post-targeted therapy era.Whether it is the 2019 European Urological Association (EAU) or the 2019 National Comprehensive Cancer Network (NCCN) guidelines, current patients in the low-risk group recommend pezopanib and sunitinib; and middle- and high-risk patients recommend cabotinib and shutinNitinib or Pezopanib.The American Society of Clinical Oncology's annual meeting on urogenital tumors (ASCO-GU), which just ended this year, brought some new advances in targeted therapy.As is known to all, mutations in the VHL gene of kidney cancer cause the hypoxia-inducible factor HIF-2ɑ signal to be over-activated. Promoting tumor cell proliferation and angiogenesis are the key molecular foundations of targeted therapy for renal cancer. Inhibition-dependent targeted therapy targets its downstream target genes.There is a lack of effective inhibitors for this key core of HIF-2ɑ.After many years of searching, it is finally dawning, MK-6482 (PT2977), as the first HIF-2 for clinical research, announced the preliminary research results at this conference.A phase I / II clinical study included 55 patients with advanced renal clear cell carcinoma. All patients had received first-line treatment and above, 62% had received third-line treatment and above, and 73% had received immunotherapy, which basically belonged toEnd-line patients.Initial results are promising: median progression-free survival (PFS) of 11 months; patients with better prognosis in the subgroup analysis had PFS of 16.5 months and were well tolerated; in addition, 24 were obtained in patients with baselineThe objective response rate (ORR) of 80% and the disease control rate (DCR) of 80% are not easy.3 In recent years, the research status of immunotherapy has become increasingly feverish. Immunotherapy has also made some progress in the treatment of advanced renal cancer, such as KEYNOTE-426, CheckMate 214, JAVELIN Renal101, and IMmotion 151. What is the guiding significance for clinical practice??The field of renal cancer immunotherapy has also been widely reported in recent years, whether it is the first report of CheckMate 214 or the follow-up studies of KEYNOTE-426, IMmotion 151, and JAVELIN Renal 101.Based on the results of the CheckMate 214 trial in 2018, the FDA approved Nivolumab + Ipilimumab for first-line treatment of advanced kidney cancer.Subsequent long-term follow-up data released by ASCO-GU in 2019 showed that the combination immunotherapy group had better OS (NR vs 26 months) and ORR (42% vs 27%) than the sunitinib group in patients at intermediate and high risk, andThere is no significant difference in OS in low-risk patients, so the 2019 NCCN and EAU guidelines are recommended for patients with high-risk.In addition, based on the results of the KEYNOTE-426 study published in the same year, the US FDA approved Pembrolizumab combined with axitinib for first-line treatment of advanced renal cancer, which has a better 12-month survival rate than the sunitinib combined treatment group (89.9%vs 78.3), median PFS (15.1 months vs 11.1 months), and ORR (59.3% vs 35.7%).The IMmotion 151 and JAVELIN Renal 101 studies, as well as the recently published Phase I / II study of Sitravatinib in combination with Nivolumab in the treatment of failed antiangiogenic treatment of renal cell carcinoma in 2020 ASCO-GU have unveiled the potential advantages of immunotherapy combined with targeted therapy.Although immunological checkpoint inhibitors have not yet been approved for the treatment of advanced renal cancer in China, comprehensive clinical studies related to existing immunotherapy suggest that combined immune checkpoint inhibitors may be more effective in patients with high-risk and low-risk patients.Anti-angiogenesis targeted therapy is recommended.In addition, immune checkpoint inhibitors in combination with anti-angiogenesis targeted drugs are also a trend in the future.4 At the EUA annual meeting last year, the urology team of Fudan University Cancer Hospital led by Professor Ye analyzed the prognosis of each stage subgroup based on the clinical follow-up data of 2120 kidney cancer patients in the past ten years, and proposed the 8th edition of AJCC renal cancer staging.Improvement plan, what is the significance of this plan for clinical practice?What are the guiding significances for the current treatment of advanced kidney cancer?First, the clinical significance of this program is that the new staging system distinguishes patients with different prognosis of kidney cancer more accurately than the old version.The fine-tuned staging system can provide more accurate prognosis predictions and better distinguish the high-risk and low-risk kidney cancer patient groups.With just one change, the prognosis of AJCC's stage staging system is improved.Accurate treatment of kidney cancer requires accurate staging as the basis for later treatment choices.Accurate prediction of the patient's prognosis plays a vital role in the follow-up treatment of renal cancer patients, especially high-risk patients.Therefore, the new staging system we have introduced has high clinical significance.Second, patients with intermediate and advanced renal cancer need no further targeted therapy. How to choose the right group is an important clinical problem.With our new staging system, we can find out more accurately the high-risk renal cancer patients with poor prognosis. These patients need timely targeted therapy or immunotherapy.In fact, some of the high-risk patients included in the original staging system have a fairly good prognosis. In our new staging system, they have been classified into the low-risk group. These patients can be followed up or they can choose whether to be as early as possible according to their own conditionsDevelop targeted therapies.This is very important for the individualized treatment of kidney cancer. It can be a meaningful task to avoid overtreatment, reduce the financial burden on patients, and reduce unnecessary medical insurance expenditures.5. At the EUA annual meeting last year, the team of Fudan University's Affiliated Tumor Hospital made a collective appearance, bringing 10 oncology-related studies to international urology colleagues.Among them, kidney cancer, bladder cancer, and prostate cancer research in the three major fields have already become leaders in the industry. Ask Professor Ye how the Fudan team led you to do it?Can Fudan Mode be shared with more colleagues?Academic research is not just for publishing articles, but for starting with solving clinical problems.Our center accumulates accumulated clinical experience and in-depth clinical findings to guide the development of scientific research, forming a closed loop in which scientific research results are transformed to serve clinical work. This is the true meaning of scientific research.Outstanding clinical research workers need to have a "scientific spirit": to study and study in an attitude that is not afraid of clouds and eyes, not to be impatient, not to be arrogant, to be down-to-earth, open-minded, asking for advice, and walking step by step.In addition, the most important thing is integrity, which is the bottom line that must be kept to the bottom.The above content is only authorized for exclusive use by, please do not reprint without the authorization of the copyright party.


The author ouyangshaoxia