Nephrectomy after immunotherapy can achieve complete response in selected patients

Delayed nephrectomy after a complete response to immune checkpoint inhibitor therapy may induce a complete response (CR) in selected patients with metastatic renal cell carcinoma (mRCC).

Among 11 patients with clear cell renal cell carcinoma who had a CR at metastatic sites following administration of immune checkpoint inhibitor therapy for a median of 10 months, 2 experienced a pathologic CR. After median follow-up of 15 months, 73% of patients were free from progression and 54% were free from systemic treatment at 1 year.

More than half of the patients, however, had inflammatory infiltration in the kidney after the long exposure to immunotherapy.

A retrospective review of data from the series of patients was announced by Géraldine Pignot, MD, at the 2020 European Association of Urology Virtual Congress.¹

Following a good response to immune checkpoint inhibition, delayed nephrectomy can help to achieve CR in selected patients, but “the long exposure [to immune checkpoint inhibitor therapy] results in challenging surgery,” she said. “This is probably different from nephrectomy following short neoadjuvant treatment.”

The paradigm for the management of mRCC has changed based on the results of the CARMENA trial, with cytoreductive nephrectomy no longer the standard of care for patients with intermediate- and poor-risk mRCC, said Pignot, urologic surgeon, Médecin Urologie Institut Paoli-Calmettes, Marseille, France. “Patients are now treated with their primary renal tumor in place and the question of delayed surgery becomes a new interest for selected patients,” she said.

In the current era of immune checkpoint inhibition, some patients have radiologic CR on metastatic sites. For such patients, the role and timing of nephrectomy is uncertain. In an attempt to clarify this role, the investigators evaluated the use of delayed nephrectomy in 11 patients (7 men, 4 women) with mRCC from 8 French centers who had a CR on metastatic sites following immune checkpoint inhibitor therapy as first- or second-line treatment.

All patients had clear cell RCC on initial biopsy. None received initial cytoreductive nephrectomy. Their median age was 59.8 years; initial T stage was T3b or T3c in 36.4%, T3a in 27.2%, T4 in 18.2%, and T2 in 18.2%. Nodal status at diagnosis was positive in 6 patients. Nine patients had 1 metastatic site and 2 had 2 or more metastatic sites. The lung was the site of metastasis in 8 patients.

International Metastatic RCC Database Consortium prognostic group was intermediate in 81.8% and poor in 18.2%. Immune checkpoint inhibitor therapy was administered as first-line therapy in 36.4% of patients (4/11) and as second line after a tyrosine kinase inhibitor in 63.6% of (7/11). Immune checkpoint treatments regimens were nivolumab (Opdivo) alone in 6 patients, nivolumab plus ipilimumab (Yervoy) in 3 patients, and nivolumab plus tivozanib (Fotivda) in 2. The median number of immune checkpoint inhibitor cycles was 27. Toxicities of any grade were experienced by 7 patients (63.6%), with grade 3/4 toxicities requiring treatment discontinuation in 3 patients (27.3%).

Tumor size decreased from a mean of 119 mm at diagnosis to 69 mm at the time of surgery. Radical nephrectomy was performed in 90.9% of the patients; and in 63.6%, an open surgical approach was used. The median operative time was 243 minutes and mean blood loss was 909 cc.

“In 81.8% of cases, surgeons experienced difficulties in finding dissection planes due to adhesions and inflammatory reactions at the kidney and the surrounding tissue,” said Pignot. “In 2 cases, the extent of surgery or the surgical approach changed during the procedure [one a switch from partial to radical nephrectomy and the other a conversion to open surgery].”

Median length of stay was 7 days. The 30-day Clavien-Dindo postoperative complication rate was 54.6%. There was one grade IIIa surgical complication, a postoperative hematoma with percutaneous drain, and one grade V complication, a death related to hemorrhage and hypovolemia.

Residual viable tumor was observed in 81.8% (9/11). The pathologic report showed lymphocyte and/or macrophage infiltration in 54.6% and a complete pathologic response rate of 18.2% (2/11).

Reference

1. Pignot G, Thiery-Vuillemin A, Walz J, et al. Nephrectomy after complete response to immune checkpoint inhibitors for metastatic Renal Cell Carcinoma (mRCC): A new surgical challenge? 2020 European Association of Urology Virtual Congress. July 17-26, 2020. Abstract 834

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