*For medical professionals reading reference only
How to choose a more suitable treatment plan for patients with advanced renal cancer who relapse after surgery?
In recent years, the diagnosis and treatment of advanced renal cancer has developed rapidly, and targeted therapeutic drugs have become increasingly abundant, which has significantly improved the survival time and quality of life of patients and has become an important treatment method for advanced renal cancer. At the same time, with the rapid development of immunotherapy in the field of renal cancer, clinical treatment methods have become more diverse. In clinical practice, how to formulate appropriate treatment plans for different patients with advanced renal cancer has become a hot topic of clinical concern. This article is a case of left renal clear cell carcinoma (ccRCC) recurrence after surgery and multiple metastasis of both lungs and thoracolumbar spine (IMDC high-risk) by Professor Lu Cuiping from the team of Director of Oncology Department of Longyan First Hospital. The diagnosis and treatment process, related basis and clinical ideas are shared, in order to provide reference and reference for the individualized comprehensive treatment and full management of advanced renal cancer.
[Statement: The case sharing and discussion involved in the meeting are for educational and communication purposes only, and do not involve consultation and intervention diagnosis and treatment. The relevant diagnosis and treatment decisions are made independently by the doctor based on the patient's condition. 】
Case introduction
Basic information
General situation: male, 53 years old, no family history of tumor.
main complaint: In February 2020, the patient was admitted to this hospital due to "increased lower back pain, inability to stand on both lower limbs, difficulty in urinating and defecation."
Current medical history:
In May 2018, the patient was diagnosed with "left kidney mass" due to repeated hematuria in naked eyes and . He went to Guangzhou Zhujiang Hospital for parallel surgical resection. The postoperative pathology was "renal clear cell carcinoma", and there was no special treatment after the operation.
In April 2019, the chess and abdomen of this hospital: 1. After left kidney cancer surgery, there were multiple nodules and clumps in the left kidney area (involving the left diaphragm, psoas major muscle and erection spinal muscle ); 2. Multiple nodules and clumps in the lower lobe of the right lung: possible metastasis.
Figure 1. Results of thoracic and abdomen CT examination in April 2019
physical examination: KPS score 70 points, percussion pain in the left kidney area is obvious, chest 11-L3 vertebrae tenderness and percussion pain are positive; muscle strength of both lower limbs level 3, muscle tone is normal, and sensory disorders in the separating lower limbs are dissociated.
assisted examination:
blood routine : leukocytes (WBC) 5.6g/L, hemoglobin (HGB) 94g/L↓, neutrophils (N) 2.18g/L, platelets (PLT) 359g/L.
Biochemistry: calcium (Ca) 2.65mmol/L↑, alkaline phosphatase (ALP) 155IU/L.
Thoracic and abdominal CT: multiple metastasis in both lungs, increasing and enlarging compared with the previous period; the kidney mass in the kidney area is further enlarged compared with the previous period.
head + thoracic lumbar spine MR: thoracic 11-lumbar 3 vertebrae and attachment bone metastasis, involving paravertebral soft tissue, partially invading the spinal canal and left intervertebral foramen, the corresponding nerve roots are invaded, the spinal cord is compressed and the signal is abnormal; no abnormalities are seen in the head.
Figure 2. Imaging results in February 2020
Diagnosis
Left renal clear cell carcinoma (T1N0M0 Stage I) recurs after surgery and multiple metastasis of both lungs and thoracolumbar spine (IMDC prognosis score: high risk); spinal cord compression syndrome.
First-line treatment: sunitinib combined with immunotherapy, PFS 4 months
Treatment plan: On February 20, 2020, the patient began oral "sunitinib 50mg qd (4/2 plan)" targeted treatment, and 4 courses of immunotherapy combined with carrilizumab from February 18 to May 5, 2020; local palliative radiotherapy for thoracic lumbar metastasis was started on March 3, 2020, and GTV-P 3000CGY/10F was given; low back pain was obvious, combined with oral oxycodone sustained-release tablets 80mg Q12H to relieve pain.
Adverse reactions: Grade 1 diarrhea occurred during treatment, 3-degree thrombocytopenia , PLT 47g/L.
reexamination enhanced CT (June 21, 2020): 1. After left renal malignant tumor surgery, there were multiple nodules and clumps in the left renal area, which was considered to have the possibility of recurrence, which was similar to the previous one; 2. Multiple metastatic tumors in both lungs, enlarged compared with the previous one; 3. Left pleural effusion and incomplete swelling of the lower lobe of the left lung, which was obvious compared with the previous one; 4. Bone destruction of the lower thoracic and upper lumbar vertebrae and swelling of the surrounding soft tissue, which was similar to the previous one; 5. No abnormalities were found in the skull CT scan.
efficacy evaluation: PD.
Figure 3. Imaging examination results on June 21, 2020
Second-line treatment: axitinib combined with immunotherapy, PFS 29 months
treatment plan: patients started oral axitinib 5mg bid targeted therapy on June 20, 2020 and continued to cooperate with PD-1 immunotherapy. Efficacy evaluation of
: 2 months after treatment (August 28, 2020) CT was found to have a pulmonary lesion and the lesion in the left kidney area shrunk compared with the previous one, and the efficacy was evaluated as PR. The dose of oxycodone sustained-release tablets gradually decreased, and oral painkillers were stopped after 4 months of treatment. The patient can walk on the ground and urinate and defecate back to normal.
Adverse reactions: Blood pressure increased during treatment, oral antihypertensive drugs can be controlled; no adverse reactions such as proteinuria were found.
Figure 4. Imaging results before and during the second-line treatment
Cases summary
renal cancer is a common malignant tumor of the urinary system in my country, and the incidence rate is on the rise year by year. In recent years, kidney cancer diagnosis and treatment have developed rapidly, from the cytokine era to the targeted therapy era, and now it has entered the era of combined immune therapy. At the same time, the diagnosis and treatment model of stratified treatment for patients with advanced renal cancer is becoming increasingly prominent. This patient has recurrence after surgery on left renal clear cell carcinoma and multiple metastasis of both lungs and thoracolumbar spine (high risk of IMDC). How can we formulate individualized and precise comprehensive treatment strategies for it in clinical practice?
IMDC high-risk population, how should I choose first-line treatment?
study shows that anti-angiogenesis treatment can normalize the abnormal tumor vascular system to increase the infiltration of immune effector cells, which is to convert the immunosuppressed tumor microenvironment into an immune-enhanced tumor microenvironment. In other words, vascular normalization can improve the efficacy of immunotherapy, which lays the theoretical foundation for the combination of immune combination to angiogenesis of . Moreover, many large-scale international randomized controlled studies such as JAVELIN Renal 101 and KEYNOTE-426 have shown that compared with the TKI single agent of vascular endothelial growth factor receptor (VEGFR), immune checkpoint inhibitor (ICI) + TKI combined with first-line treatment significantly improves the survival benefits of advanced renal cancer; especially for high-risk groups in IMDC, target-free combination therapy has greater survival benefits [1,2]. A real-world study released at the 2022 American Society of Clinical Oncology Annual Meeting on Urenogenital System Tumors (ASCO-GU) analyzed the survival benefits of dual-immunity (IO-IO), target-immunity (TKI+IO) and single-immunity (TKI) under different treatment modes. It was found that the survival benefits of TKI+IO first-line treatment are greater and can better improve the treatment outcomes [3].
2022 V3 version of the National Comprehensive Cancer Network (NCCN) pointed out that advanced renal cancer has entered the era of combined immune system and that first-line target-free combined treatment of high-risk groups will obtain the preferred recommendation for guidelines for obtaining guidelines for high-risk populations. In addition, the 2022 Chinese Society of Clinical Oncology (CSCO) guidelines point out that metastatic renal cancer is divided into low-risk, medium-risk, and high-risk according to the prognosis model of MSKCC or IMDC. The corresponding population has different characteristics of biological . More and more evidence shows that stratified treatment is needed. Low-risk populations are more suitable for targeted treatment, while medium- and high-risk populations are difficult to treat, and combined immunotherapy may be required for [5].
According to this, this case of patients with left renal clear cell carcinoma recurrence after surgery and multiple metastasis of both lungs and thoracolumbar spine (IMDC high risk) were treated with PD-1 inhibitor + sunitinib in combination. In addition, although traditional concepts believe that renal cancer is not sensitive to chemoradiotherapy, with the development of radiotherapy technology, the value of radiotherapy in renal cancer has also been reflected, especially in patients with brain metastasis and vertebral metastasis, local palliative radiotherapy combined with targets can achieve better relief. Therefore, the patient received local palliative radiotherapy for the thoracic and lumbar metastasis during the first-line target-free combination treatment. Unfortunately, after a review of 4 months later, it was found that the case had multiple metastatic tumors in both lungs in this case were larger than before, and the left pleural effusion and incomplete swelling of the lower lobe of the left lung were significantly higher than before, and tumor PD.
It should be pointed out that although target-free combination therapy has been recommended by foreign guidelines, ICI has not been approved for first-line renal cancer treatment indications in China, which has brought certain restrictions on the formulation of clinical treatment plans. What is the real-world research situation in China with first-line target-free combined treatment? More exploration is needed in the future.After the first-line target treatment progress is progressing, which solution is more appropriate for the second-line choice?
renal carcinoma occurs related to the loss of function of the VHL gene. The loss of function of this gene leads to abnormal regulation of the VEGF pathway, making advanced renal cancer a vascular-rich tumor. Preclinical studies have shown that advanced renal cancer that progresses after TKI treatment still has continuous angiogenesis, and tumors are still sensitive to inhibition of VEGF signaling pathways. VEGFR is an important therapeutic target.
International Multicenter Phase III INTORSECT study showed that after the progress of sunitinib treatment in patients with metastatic renal cell carcinoma, sequential VEGFR-TKI significantly prolonged OS compared with mTOR inhibitors (16.6 months vs 12.3 months) [6]. A Czech real-world study (RENIS) included data from , using common sequential treatment regimens (including sunitinib-axitinib, sunitinib-everolimus, pezopanib-everolimus and pezopanib-sunitinib) between , and February 2018. The analysis found that the OS of other sequential treatment regimens were inferior to those of sequential treatment regimens after first-line resistance to sunitinib [7]. Moreover, SWITCH studies showed that there was no toxic accumulation in sequential treatment of TKI-TKI, and the incidence of in major grade 3/4 adverse events did not increase. In addition, the latest results of KEYNOTE-426 and other studies released at the 2022 American Society of Clinical Oncology (ASCO) Conference suggest that immune or combined immune therapy is an important choice after the failure of TKI treatment, and TKI continues to benefit as a sequential treatment after the failure of immunotherapy [8,9].
Axitinib is a new generation of oral VEGFR inhibitors, which has a stronger inhibitory effect on VEGFR-2; and, axitinib is highly selective for VEGFR-2, has low off-target effect, and is not easy to cause related adverse events. After comprehensive consideration, the patient was treated with second-line axitinib combined with PD-1 inhibitor. After 2 months of treatment, a follow-up CT showed that the lung lesions and left kidney area lesions were smaller than the previous one, and the efficacy was evaluated as PR; after 4 months of treatment, the patient stopped taking oral painkillers, was able to walk on the ground, and urinated and defecated back to normal. As of November 2022, the case has reached nearly complete clinical remission (CR), with PFS for 29 months and is expected to benefit longer in survival. Moreover, during the treatment process, the patient's tolerance can be achieved, and only blood pressure increases occur, and oral antihypertensive drugs can be controlled. It can be seen that in the real world, second-line treatment of axitinib + PD-1 inhibitor can significantly improve the survival time and quality of life of patients with advanced renal cancer, and at the same time it is good in safety, which is a preferred clinical treatment plan.
Although the second-line treatment options for advanced renal cancer are gradually becoming rich, there are still many clinical issues that need to be further explored, such as whether it is necessary to add gene detection to find effective biomarkers and guide treatment options. In the future, we look forward to the continuous improvement of the comprehensive benefits of patients with advanced renal cancer with the development of more clinical research and the accumulation of clinical drug experience.
Expert Profile
Zhan Ying Professor
Longyan First Hospital
Chief physician
Fujian Provincial Lung Cancer Professional Committee
Fujian Provincial Breast Diseases Committee
Fujian Provincial Breast Diseases Committee Deputy Leader
Fujian Provincial Lymphoma Professional Committee
Fujian Provincial Tumor Psychological Committee Standing Committee
Fujian Provincial Oral Tumor Professional Committee Standing Committee
Fujian Provincial Oral Tumor Professional Committee Standing Committee
Fujian Straits Tumor Association Precision Medicine Professional Committee Member
Shanghai Fudan University Affiliated Cancer Hospital, Fujian Provincial Cancer Hospital Research Experience
2018 United States MD Anderson Visiting scholars at the Tumor Center
are good at standardized diagnosis of malignant tumors such as lung cancer, breast cancer , and digestive tract, as well as individualized chemotherapy, molecular targeting, immune and palliative treatments.
Expert profile
Lu Cuiping Professor
Daoshima Department of Oncology, Longyan First Hospital
Deputy Chief Physician Master's degree
Fujian Anti-Cancer Association First Cancer Professional Committee
Fujian Strait Medical and Health Exchange Association Oncology Diagnosis and Treatment Branch Rare Targets Member
Fujian Strait Medical and Health Exchange Association Oncology Diagnosis and Treatment Branch Director
Fujian Strait Medical and Health Exchange Association Nutritional Branch Director
Fujian Strait Medical and Health Exchange Association Clinical Research Cooperation Branch Member
Fujian Strait Medical and Health Exchange Association Clinical Research Cooperation Branch
Hong Kong Medical Association Oncology Branch Standing Committee
References
[1].Motzer RJ, et al. N Engl J Med, 2019,380 (12): 1103-1115.
[2].Rini BI, et al. N Engl J Med, 2019,380 (12): 1116-1127.
[3].Matthew Scott Ernst, et al. ASCO GU 2022. Abstract 308.
[4].NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) Kidney Cancer. Version 3. 2022.
[5].2022 version of the Chinese Society of Clinical Oncology (CSCO) Renal Cancer Diagnosis and Treatment Guide.
[6].Hutson TE, et al. J Clin Oncol. 2014;32(8):760-7.
[7].Eichelberg C, et al. Eur Urol. 2015;68(5):837-47.
[8].Thomas Powles et al. 2022 ASCO. abstract 4513.
[9].Kalirai A, et al. ASCO GU 2022. Poster 346.
*This article is only used to provide scientific information to medical personnel and does not represent the views of this platform
