Editor's note: The 39th annual meeting of the European Association of Urology (EAU24) took place from April 5th to 8th, in Paris, France, focusing on global urological oncology hot topics and cutting-edge progress by Chinese urologists. Among the many discussions at the conference, a significant focus was on integrated treatments for renal cancer. "Oncology Frontier" invited Dr. Jianming Guo from Zhongshan Hospital Fudan University and Dr. Riccardo Campi from Careggi Hospital, University of Florence, to share insights on the topic.
Dr. Jianming Guo
Zhongshan Hospital Fudan University, Dept. of Urology, Shanghai, China
Dr. Riccardo Campi
Careggi Hospital, University of Florence, Florence, Italy
Oncology Frontier: Both of you have had research accepted at this EAU conference. Could you each share about your reported research?
Dr. Riccardo Campi: I am pleased and honored to share the research outcomes presented at the EAU conference here. The study on quality indicators for renal cancer surgery was led by the EAU Young Urologists Kidney Cancer Working Group, analyzing whether quality indicators could be used to evaluate renal cancer surgeries. We have selected various quality indicators, especially “the proportion of patients with cT1-2N0M0 renal masses undergoing partial nephrectomy, whether minimally invasive or open.”
These quality indicators were analyzed in a large multi-institutional database, namely the Young Academic Urologists Cancer Retrospective Database. The findings show that most patients with cT1a renal tumors underwent partial nephrectomy. Minimally invasive surgery is the gold standard for T1-T2 renal cancer nephrectomy and radical nephrectomy. However, only two-thirds of patients with localized cT1b renal tumors underwent partial nephrectomy, indicating that surgical decisions in this cohort still require further scrutiny; it highlights the need for further improvements in managing larger renal tumors and applying quality indicators to assess urological surgeons’ performance.
Dr. Jianming Guo: Our team reported at this year’s EAU conference on the application of artificial intelligence in predicting renal cancer imaging assessments. We gathered CT images from multiple centers and conducted deep learning with artificial intelligence. We hope to address two clinical pain points: First, how to accurately determine the benign or malignant nature of renal tumors using CT imaging. For benign or small-volume tumors, it is actually possible to monitor them without immediate surgery; or for larger tumors that we can determine to be benign, we should aim to perform nephron-sparing surgery as much as possible to avoid unnecessary radical nephrectomy. Second, by learning the CT characteristics through artificial intelligence and combining them with other clinical features, we aim to predict the aggressiveness of the tumor and the patient’s prognosis. If the tumor is highly malignant and has a high risk of metastasis or recurrence, should we opt for partial nephrectomy or radical nephrectomy?
Based on these two issues, we developed a predictive model using artificial intelligence and deep learning of CT imaging, which has shown good diagnostic performance with a high AUC value. I also conducted external validation, comparing the model with 7 radiologists, and the results showed that the model’s predictions were superior to those of 6 of the doctors. This preliminary research indicates that this AI diagnostic model for imaging has potential for wider application. In the future, we hope to further validate this research and apply this technology in areas with limited resources or less clinical experience, such as the Midwest, to help improve their diagnostic capabilities.
Oncology Frontier: Dr. Campi participated in a discussion during the “Thematic Session” on how to manage complex cystic renal cancer. Could you share further with our readers your views on this issue?
Dr. Riccardo Campi: As we know, this is one of the most controversial topics in the field of localized renal tumors. Diagnosing and staging cystic renal cancer is particularly challenging, and the decision-making process differs significantly from other renal tumors. Whether active surveillance can achieve the same oncological outcomes as partial or radical nephrectomy, especially in cases of Bosniak III cysts where the benignity or malignancy of the tumor is more uncertain. In my presentation, I advocated for the role of surgery in treating cystic renal masses, particularly for Bosniak IV cysts. We also analyzed a cohort of patients operated on at Careggi University Hospital in Florence, half of whom had Bosniak IV renal cysts and the other half Bosniak III. In Bosniak IV cysts, over 90% of the patients had malignant renal tumors, and until we have clearer biomarkers or more accurate imaging methods, surgery remains the best treatment option. Additionally, I discussed the role of active surveillance for Bosniak III cysts smaller than 4 cm, where monitoring their growth pattern and imaging evolution is feasible before making a joint decision with the patient about surgery.
Oncology Frontier: Dr. Guo’s team developed the renal cancer surgery scoring system “ZS Score”. Can this scoring system also be used to assess cystic renal cancer? Could you share your experience with managing complex cystic renal cancer?
Dr. Jianming Guo: The main international renal cancer surgery scoring system is the RENAL system, which primarily judges based on the size of the tumor. Obviously, this single-factor scoring system is insufficient, as when a renal tumor is large and mainly protrudes outward from the surface of the kidney, the difficulty of nephron-sparing surgery is not very high. Conversely, if the renal tumor is not very large but is located deep within the kidney, the difficulty of partial nephrectomy is higher. Thus, we developed the “ZS Score” scoring system, where ZS stands for Zhongshan Hospital. Our scoring system, in addition to tumor size, also considers other factors such as tumor depth and location.
Of course, I want to emphasize that performing a biopsy on cystic renal cancer is undoubtedly “disastrous”, and these types of tumors are also not recommended for puncture biopsy. Therefore, we may need more imaging diagnostic evaluation indicators for cystic renal cancer, including the tools mentioned earlier, using AI and deep learning of CT imaging for diagnosis and prognosis assessment. Preoperative differential diagnosis of cystic renal cancer deserves our close attention.
Oncology Frontier: Dr. Campi also delivered a lecture on the future of immunotherapy for localized renal cancer. We know that currently only KEYNOTE-564 has shown positive results, while several large phase 3 studies have failed. How do both of you view the prospects of early-stage renal cancer immunotherapy?
Dr. Riccardo Campi: This is indeed one of the most exciting topics in the field of renal cell carcinoma today. The role of perioperative immunotherapy, especially the role of adjuvant immunotherapy in high-risk renal cell carcinoma, remains controversial. Based on the results of the KEYNOTE-564 trial, we observed a significant DFS benefit with the use of pembrolizumab as adjuvant therapy after surgery. This trial also showed for the first time a benefit in overall survival (OS, HR 0.62, P=0.0024) in the field of adjuvant immunotherapy for renal cell carcinoma. However, we also face contradictory evidence, as several trials on the use of other drugs, including PD-L1 inhibitors in adjuvant therapy, have failed. As clinicians, it becomes crucial to select patients who are most likely to benefit from adjuvant therapy, understanding which patients have a long enough expected survival to benefit from treatment.
In this challenging era with mixed evidence, we are striving to understand why only one trial was positive while others failed. We need to work towards shared decision-making, helping patients understand the risks of overtreatment and adverse events from immunotherapy, while offering a chance for cure and improved OS rates to high-risk renal cell carcinoma patients. If you have seen an article in The New England Journal of Medicine, it detailed the patients who benefited the most, and the data provided at this year’s ASCO GU also showed benefits in OS for M0 patients. The variations in trial results may be attributed to differences in study populations and other characteristics, such as study design, timing of treatment, and treatment-related side effects. The reasons for differing outcomes may be multifaceted.
Dr. Jianming Guo: For high-risk localized renal cancer, how to perform adjuvant therapy post-surgery to reduce the risk of recurrence is one of the hotly debated topics in the clinic. Earlier, renal cancer adjuvant therapy mainly involved cytokines, and later, exploration of small molecule tyrosine kinase inhibitors (TKIs) like pazopanib, but these generally failed, showing no significant improvement in disease-free survival (DFS). However, following the great success of immunotherapy in advanced stages, KEYNOTE-564 achieved results in renal cancer adjuvant therapy for the first time, showing significant improvement in DFS (HR=0.68, P=0.0164). This result is encouraging and provides a new adjuvant immunotherapy option for post-operative high-risk localized renal cancer patients.
I think two important factors contributed to the success of this study: first, it included patients with M1 and no evidence of disease (NED) who achieved no residual disease post-surgery; second, the study cohort included many patients with sarcomatoid features or tumor necrosis. Both groups of patients have relatively poor prognosis and high recurrence risk. If they achieve surgical cure and receive intensified adjuvant treatment, they are likely to benefit from survival gains and achieve a significant difference compared to the control group. As Professor Campi introduced, a post hoc analysis of M0 patients was also conducted at this conference, as these patients have a relatively better prognosis, and the study results showed that age and tumor necrosis are important factors affecting treatment benefits. Overall, the results of KEYNOTE-564 are encouraging, and more patients will benefit from adjuvant immunotherapy, hoping to achieve better survival improvements.
Oncology Frontier: We know based on the CARMENA study, for MSKCC high-risk patients, the EAU guidelines no longer recommend cytoreductive surgery. But as advanced renal cancer has entered the era of immunotherapy, do both of you believe there is still a role for cytoreductive surgery? What is the optimal timing for surgery?
Dr. Riccardo Campi: This is another highly challenging issue in the field of renal cell carcinoma. The first point I want to emphasize is the need for multidisciplinary decision-making in such cases. I believe newly diagnosed metastatic cancer patients should definitely be managed by a multidisciplinary team, including urology, medical oncology, radiology, and radiotherapy, to better understand tumor staging and treatment options, including radical surgery, cytoreductive nephrectomy, stereotactic body radiation therapy (SBRT), and immune or targeted therapies.
For clear cell RCC, combinations of immunotherapy have become the standard of care. For individual patients, understanding the risk is crucial, and risk classification should be based on scores recommended by IMDC, MSKCC, etc. If the patient indeed requires systemic therapy due to a high metastatic burden, systemic treatment should be prioritized. If systemic therapy is effective and achieves good remission, then delayed cytoreductive surgery post-immunotherapy can be considered. Although from a surgical standpoint, the difficulty may increase due to adhesions and fibrosis after systemic treatment. However, for patients with low tumor burden and more inclined to low-moderate risk, I still believe that cytoreductive surgery should precede systemic therapy, especially on how to combine it with SBRT, which can clear or control most metastatic sites. In conclusion, a personalized and risk-based approach is necessary for each patient, and in such cases, multidisciplinary decision-making is absolutely key.
Dr. Jianming Guo: I also agree with your view, as this is a complex issue and actually an evolving process. Before the CARMENA and SURTIME studies, many renal cancer treatments were still led by surgeons, who advocated for post-surgical systemic treatment. After these studies were published, although they had certain limitations, the overall trend, as Professor Campi introduced, leans towards systemic treatment first for patients with medium to high risk or high tumor burden, and those who respond well to therapy may undergo cytoreductive surgery. Overall, the effect of pure drug treatment is not worse than that combined with cytoreductive surgery, which means we need to more precisely screen for populations that would benefit from cytoreductive surgery.
Therefore, there will no longer be a “one-size-fits-all” approach clinically, and we advocate for multidisciplinary discussions and individualized decision-making based on the specific situation of the patient. Patients with higher risk stratification and poor physical condition should prioritize systemic treatment. On the other hand, for patients with low to moderate risk, especially those with oligometastases, I believe cytoreductive surgery is still viable. But in the era of immunotherapy, relatively more patients may start with systemic therapy first, because from some studies reported at this year’s EAU, starting with immunotherapy, achieving tumor shrinkage, and then performing curative resection or nephron-sparing surgery, this strategy of delayed cytoreductive surgery post-immunotherapy is feasible.
TAG: EAU24 Interview, Renal Cancer, immunotherapy
