EMUC17: Difficulties in identifying the optimal approach in kidney cancer

The second day of EMUC17 kicked off with pitfalls and clinical challenges in managing oligometastatic kidney cancer. Experts examine issues such as the optimal timing of cytoreductive nephrectomy, developments in adjuvant therapy, promising biomarkers for decision-making and the role of local radiation therapy.

Chaired by Thomas Powles (GB), Vincent Khoo (GB), Hein Van Poppel (BE) and Ferran Algaba (ES), the session also tackled two real-life cases for discussion which were presented by Umberto Capitanio, (IT) who posed queries to the audience and the expert panel for them to comment on. The questions, with digital voting and feedback from the audience, demonstrated the pitfalls in diagnosis and treatment, which prompted some of the panel experts and chairs to caution the audience regarding choosing either a radical or passive strategy that may not necessarily find solid support in evidence-based medicine.

Alex Bex (NL) gave a comprehensive overview on the role of cytoreductive nephrectomy (CN) and discussed issues such as post-operative follow-up after CN. In his concluding remarks he said patients with oligometastatic disease (with the primary tumor in place) should undergo CN and be carefully observed after surgery. He added that data of the only currently available randomized study support that those requiring systemic therapy with VEGFR-TKI should be offered deferred CN.

“The deferred CN approach appears to select out patients with inherent resistance to systemic therapy. This confirms previous findings from single-arm phase 11 studies,” said Bex.

Capitanio discussed the recent gains in adjuvant therapy for patients with kidney cancer. He said that based on available data, adjuvant therapy is affected by significant toxicity and there is no benefit for the majority of high-risk M0-RCC patients.

However, a non-negligible proportion of high–risk patients (pN1) harbor early systematic dissemination with very poor survival prognosis. In this specific scenario, adjuvant therapy might show the highest ratio between clinical benefit and costs (toxicity), said Capitanio. Lymph node dissection in the high-risk M0 scenario does remain a key tool to identify the best candidates for adjuvant therapy.

Kerstin Junker (DE) gave the affirmative reply to the question whether prognostic biomarkers are ready to use. “There are validated biomarkers in independent cohorts, signatures are used…but we have several tasks such as performing prospective trials, standardized sampling and we have to take into account that we should have standard techniques.”

Piet Ost (BE) discussed whether local ablation can delay the use of systemic therapy for oligo-metastatic disease. “Metastasis-directed therapy (MDT) is an option in oligometastatic RCC, especially for solitary lesions and non-symptomatic patients,” he said.

He added: “Surgery has more complications and if histology is warranted, choose surgery. There are still open questions such as MDT only, or MDT followed by standard of care (SOC) or SOC followed by MDT in non-progressors.

Case discussions reveal pitfalls

The two case discussions with audience voting and feedback demonstrated the common pitfalls in diagnostic and treatment approaches. Capitanio presented the following real-life case to the audience for voting: A very young male, 4 cm precaval lymphadenopathy, and although a high-risk profile, CT and bone scans were negative.

Capitanio enumerated three options to the audience on how they would consider the patient, and the voting results showed:

• 66% voted for Locally-advanced disease only, non-metastatic (cT3aN1M0)
• 16% for Locally-advanced with abdomen metastases only (cT3a N1 M1)
• 18% for Already a systemic disease (micro) metastatic (cT3a N1 M1m)

In the discussion, Bex noted that although it may seem, at first glance, a case of locally-advanced disease, there are cases in current literature that show aggressive or systemic disease, which proved to be the case presented by Capitanio as the final pathology report showed the following: Papillary type 2 RCC, pT3a G3 pN1 (11 pos/15), Sinus fat invasion- Yes, Perinephric fat invasion- Yes, Necrosis- Yes and Renal vein invasion- Yes.

After the histology report, the voting changed to:

• 48% for Already a systemic disease (micro) metastatic (cT3a N1 M1m)
• 37% for Locally-advanced disease only, non-metastatic (cT3aN1M0), and
• 15% for Locally-advanced with abdomen metastases only (cT3a N1 M1)

The voting continued to the treatment strategy after surgery, which showed that 58% would go for medical therapy (adjuvant), 38% for ‘Only follow-up,’ and a small minority of 3% for retroperitoneal radiotherapy (adjuvant).

The audience feedback and panel discussion examined various treatment scenarios such as adjuvant radiotherapy, the role of biomarkers, and follow-up salvage treatment.

Capitanio provided the actual or real-life decisions taken up by the attending doctors who conducted body CT-scan at three, six and nine months after surgery and which showed multiple retroperitoneal lymphadenopathies and neoplastic caval thrombus. Salvage treatment was given using sunitinib but it was interrupted after the patient developed severe rash and asthenia.

A second-line agent (temsirolimus) was well-tolerated at the sixth month, but at the ninth month the patient developed multiple metastases in the liver and pancreas. The patient later died 11 months after the surgery.

The ensuing commentaries revealed the difficulties in identifying what is the optimal approach considering the aggressiveness of the disease. Bex and Powles underlined the necessity of finding a balance between surgical as against systemic approaches. Ost, meanwhile, commented that there is no role for adjuvant RT considering disease extent.