About Prof. Ye Dingwei
Prof. Ye Dingwei is a renowned urologic oncologist at Fudan University Shanghai Cancer Center — one of China's foremost institutions for oncological surgery, urologic cancer management, and multidisciplinary cancer care. He specialises in the surgical and comprehensive treatment of prostate, bladder, and kidney cancers, and is a national leader in robotic-assisted urologic oncology surgery. His clinical philosophy holds that in advanced urologic malignancy, the surgeon's role is not simply to operate — it is to lead a multidisciplinary team in designing a sequenced strategy that creates the conditions for surgery to succeed, and to execute that strategy with the precision and adaptability that complex oncology demands.
Case Overview
Ms. Li (pseudonym), a 27-year-old woman, presented with worsening flank pain and was found on whole-body PET-CT to have a large left renal tumour measuring 98 mm, with tumour thrombus extending into the renal vein and inferior vena cava, and systemic metastases involving hepatic nodules, pulmonary hilar lymph nodes, and bone. Left renal core needle biopsy confirmed renal cell carcinoma with features consistent with FH-deficient renal cell carcinoma — hereditary leiomyomatosis and renal cell carcinoma (HLRCC), a rare and aggressive hereditary subtype with distinct biological behaviour and therapeutic implications. Having been told at multiple institutions that curative options were unavailable, Ms. Li and her family sought Prof. Ye Dingwei at Fudan University Shanghai Cancer Center. Following multidisciplinary tumour board review, the team formulated a sequenced strategy: stereotactic body radiotherapy (SBRT) for bone metastases, genotype-directed targeted therapy and immunotherapy to downstage the primary tumour and systemic disease, and cytoreductive nephrectomy once resectability criteria were met. After five months of systemic treatment, the primary tumour and venous thrombus had reduced by nearly 50%, and hepatic metastases had halved. Left nephrectomy was performed successfully; intraoperative pathology reconfirmed HLRCC, and retroperitoneal lymph nodes were negative for metastatic disease. Postoperative targeted therapy and immunotherapy were continued. Disease was effectively controlled and Ms. Li's quality of life significantly restored.
Diagnostic Workup
Whole-body PET-CT characterised the primary left renal tumour (98 mm), defined the extent of renal vein and inferior vena cava tumour thrombus, identified hepatic metastatic nodules, pulmonary hilar lymphadenopathy, and osseous metastases, and provided a baseline for treatment response assessment. Left renal core needle biopsy confirmed renal cell carcinoma; histological and immunohistochemical profiling identified features consistent with FH-deficient renal cell carcinoma (HLRCC). Germline and somatic genetic testing confirmed FH gene mutation, establishing the hereditary diagnosis and informing targeted therapy selection — HLRCC-associated RCC demonstrates distinct sensitivity to MET-pathway inhibitors and combination immunotherapy regimens compared with clear cell RCC. Multidisciplinary tumour board review — urology, medical oncology, radiation oncology, nuclear medicine, pathology, and radiology — assessed oncological staging, surgical feasibility, systemic treatment options, and the sequenced treatment strategy.
Prof. Ye's pre-treatment assessment: The diagnosis of HLRCC-associated renal cell carcinoma changes the therapeutic calculus entirely. This is not clear cell RCC — the biology is different, the sensitivity profile is different, and the standard first-line regimens for metastatic RCC are not the right starting point. The genetic result gives us a target. The question is whether we can use systemic therapy to downstage the primary tumour and the venous thrombus sufficiently to make surgery safe and oncologically meaningful. If we can achieve that, surgery gives this patient a chance that systemic therapy alone cannot.
Treatment Strategy and Course
Diagnosis: Advanced Left Renal Cell Carcinoma (HLRCC-associated, FH-deficient) with Renal Vein and IVC Tumour Thrombus, Hepatic, Pulmonary Hilar, and Osseous Metastases in a 27-year-old patient.
Treatment principle: multidisciplinary sequenced strategy — genotype-directed systemic therapy and SBRT to achieve tumour downstaging, followed by cytoreductive nephrectomy once resectability criteria were met, with continuation of systemic therapy postoperatively.
- Phase 1 — Bone metastasis management (concurrent with systemic therapy): Stereotactic body radiotherapy (SBRT) delivered to osseous metastases to control pain and prevent pathological fracture; bisphosphonate therapy initiated for bone protection
- Phase 2 — Genotype-directed systemic therapy: Targeted therapy selected based on FH mutation profile and HLRCC biology; immunotherapy combined per MDT recommendation; serial imaging at 6–8 week intervals to assess response
- Response assessment (Month 5): Primary tumour reduced from 98 mm to approximately 50 mm; renal vein and IVC tumour thrombus reduced by nearly 50%; hepatic metastatic nodules reduced by approximately 50%; pulmonary hilar lymphadenopathy stable; MDT confirmed resectability criteria met
- Cytoreductive left nephrectomy: Complete resection of the primary tumour with tumour thrombus; intraoperative frozen section reconfirmed HLRCC diagnosis; retroperitoneal lymph node dissection — all nodes negative for metastatic disease; no intraoperative complications
- Postoperative systemic therapy (ongoing): Targeted therapy and immunotherapy continued postoperatively; surveillance imaging scheduled at regular intervals; disease effectively controlled; quality of life significantly restored
Prof. Ye's clinical reflection: The five months of systemic therapy before surgery were not a delay — they were the preparation that made surgery possible and meaningful. The tumour thrombus reduction was the critical determinant: a thrombus extending into the IVC at presentation carries substantial surgical risk; a thrombus that has responded to systemic therapy is a fundamentally different operative challenge. The negative lymph nodes at surgery were an additional finding that changed the prognostic picture. This patient came to us having been told there was no option. The multidisciplinary process gave her one.
Expert Commentary — Prof. Ye Dingwei
1. HLRCC-Associated Renal Cell Carcinoma: Genetic Diagnosis and Therapeutic Implications
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is caused by germline mutation of the fumarate hydratase (FH) gene and is associated with a distinct and aggressive renal cell carcinoma subtype that differs fundamentally from clear cell RCC in its biology, natural history, and therapeutic sensitivity. HLRCC-associated RCC tends to present at a younger age, with larger tumours and a higher propensity for early metastasis — features that were all present in Ms. Li's case. Critically, HLRCC-associated RCC does not respond reliably to the VEGF-pathway inhibitors that form the backbone of first-line therapy for clear cell metastatic RCC. The FH mutation drives metabolic reprogramming through the accumulation of fumarate, which activates the MET signalling pathway — establishing MET-directed therapy as the rational targeted approach. Accurate histological and genetic diagnosis is therefore not an academic exercise in this context: it is the prerequisite for selecting a systemic therapy regimen with a meaningful probability of response.
2. Neoadjuvant Systemic Therapy and Cytoreductive Nephrectomy in Metastatic RCC: Sequencing for Surgical Feasibility
The role of cytoreductive nephrectomy in metastatic renal cell carcinoma has been refined substantially by the targeted therapy and immunotherapy era. The contemporary rationale for nephrectomy in the metastatic setting rests on patient selection and treatment sequencing: surgery is most likely to benefit patients in whom systemic therapy has demonstrated disease control, tumour downstaging has reduced operative risk, and the primary tumour burden is disproportionate to the metastatic burden. In Ms. Li's case, the venous tumour thrombus was the primary determinant of surgical risk and complexity. Thrombus extending into the IVC requires careful surgical planning, potential vascular control, and carries risks of haemorrhage and thromboembolic complications that are substantially reduced when the thrombus has responded to systemic therapy. The 50% reduction in thrombus extent achieved over five months of treatment transformed the operative risk profile and made a procedure that would have been extremely high-risk at presentation into one that could be executed safely.
3. Multidisciplinary Tumour Board Coordination in Complex Urologic Oncology
The management of advanced urologic malignancy with systemic metastases, venous tumour thrombus, and a rare hereditary subtype requires a level of multidisciplinary integration that cannot be replicated by sequential specialist referral. In Ms. Li's case, the tumour board brought together urology, medical oncology, radiation oncology, nuclear medicine, pathology, and radiology — not to divide the patient's care into sequential episodes, but to design a unified strategy in which each intervention was sequenced to create the conditions for the next. The radiation oncologist's SBRT plan addressed bone pain and fracture risk while systemic therapy was initiated. The medical oncologist's genotype-directed regimen was selected in direct dialogue with the pathologist's molecular findings. The surgeon's decision to proceed to nephrectomy was made on the basis of imaging reviewed jointly with radiology and medical oncology. This integration — across specialties, across the five months of treatment, and through to the operative and postoperative phases — is the organisational basis for the outcome Ms. Li achieved.
How CMCS Shanghai Coordinated This Case
CMCS Shanghai supported Ms. Li and her family throughout the diagnostic, treatment, and surgical pathway at Fudan University Shanghai Cancer Center, including: priority consultation coordination with Prof. Ye Dingwei's team and the multidisciplinary tumour board; bilingual interpretation across all MDT discussions, treatment planning consultations, and follow-up appointments; bilingual explanation of the HLRCC diagnosis, its genetic implications, the sequenced treatment strategy, and each adaptive decision; coordination of PET-CT imaging, renal biopsy, genetic testing, and specialist assessments with bilingual results communication; bilingual consent for each treatment phase including SBRT, systemic therapy, and nephrectomy; intraoperative and postoperative coordination including pathology results, lymph node findings, MDT recommendations, and surveillance scheduling; and ongoing postoperative follow-up coordination including systemic therapy continuation and imaging surveillance.
For international patients facing advanced or rare urologic malignancies, Prof. Ye Dingwei's team at Fudan University Shanghai Cancer Center offers access to one of China's most experienced multidisciplinary urologic oncology programmes. CMCS ensures that expertise is accessible — in the patient's language, with every step coordinated and communicated clearly.
This case report is de-identified and published for educational purposes. All clinical details have been anonymized in accordance with patient privacy standards. CMCS Shanghai is a medical concierge service and does not provide direct medical care.
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