1. Susman, Ed

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SAN FRANCISCO-Years after successful treatment for kidney cancer, the disease may return-in one case, 29 years later-prompting researchers to suggest that clinicians be vigilant in this patient population (Abstract 541).

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"We had eight very late recurrences among the 502 patients that we followed who were clear of cancer for at least 10 years," said John Kucharczyk, a third-year medical student at the University of Queensland School of Medicine at the Ochsner Clinical School, New Orleans.


"Even if you think you have achieved a cure with initial treatment, you have to realize that these individuals are at a life-long risk of recurrence," Kucharczyk told OT at his poster presentation.


The metastases that recur, he said, appear to represent an indolent form of cancer. "Because these cancers took so long to manifest themselves, it is likely they were in some place where the microenvironment prevented growth, and therefore these patients can expect a better outcome," he said.


Metastatic Sites

The cancers that recurred were found by histology to be clear cell carcinoma in all eight cases; and all of the patients were found to have more than one metastatic site. The metastases were found in:


* the lungs in six patients;


* the bone in four patients;


* the pancreas in three patients;


* the kidney in two patients;


* the adrenal glands in two patients; and


* in other organs in five patients.



In seven of the eight cases, the tumor characteristics were considered favorable by the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and Memorial Sloan-Kettering Cancer Center risk criteria.


"The high metastatic burden and wide distribution of metastases suggest that diagnostic procedures capable of detecting recurrence in all organs may be taken into consideration during surveillance," Kucharczyk said.


"Late recurrence renal cell carcinoma is associated with favorable patients and tumor characteristics, as well as an improved response to targeted therapy when compared with early relapse patients," the researchers reported.


Patient Information

In performing the study, Kucharczyk and his colleagues collected data on consecutive patients with metastatic renal cell carcinoma who had disease recurrence more than 10 years after nephrectomy. The median time to recurrence was 16.7 years, and for this study ranged from 11.7 years to 29 years. The patients who recurred were a mean age of 77 years, and six of them were men.


Four of the very late relapse patients were treated with pazopanib, and that treatment resulted in one partial response judged on RECIST (Response Evaluation Criteria in Solid Tumors) and in three patients exhibiting disease stabilization. The mean progression-free survival was 613.5 days.


Two patients were treated with sunitinib, and these patients achieved stable disease and a mean progression-free survival of 700.5 days.


The remaining two patients underwent therapy with cytokines. One patient achieved stable disease; the other had progressive disease. The mean progression-free survival for these patients was 103 days.


The median overall survival for all eight patients was 46.6 months; the three-year overall survival was 63 percent, Kucharczyk reported. Four of these eight patients have died.


The common adverse events to the targeted therapy were fatigue, experienced by seven of the eight patients; anorexia, experienced by three patients; and diarrhea, experienced by four patients. All but one of the adverse events were Grade 1 or Grade 2 episodes.


Further Validation Needed

In commenting on the study, Xinhua Zhu, MD, attending physician in Genitourinary Medical Oncology at Northwell Health Cancer Center in Lake Success, New York, told OT that the study does not appear to change overall surveillance patterns for patients who have been treated for renal cell carcinoma.


"Given that only eight total cases were identified, I think the clinical outcomes need to be further validated in the future," Zhu suggested. "However, the data revealed interesting findings in which the patients with localized renal cell carcinoma have a life-long risk of recurrence and more favorable clinical outcomes. In the precision medicine era, the biology of very late relapse renal cell carcinoma must be distinct from patients who do not relapse and those patients who experience early relapse group."


It could be possible, he said, to develop early molecular biomarkers that might be prognostic in determining who will relapse by performing next-generation sequencing comparing no relapse and early relapse groups.


Zhu said the treatment of the patients who do relapse very late should follow current practice guidelines.