By injecting a fluorescent dye into the prostate drainage system, lymph nodes that may contain microscopic cancers can be identified and dissected and other lymph nodes can be spared, according to data reported at the Genitourinary Cancers Symposium. The meeting is co-sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology and the Society of Urologic Oncology.
Stephan Hruby, MD, Vice Chairman of the Department of Urology at Paracelsus Medical University in Salzburg, Austria, said that he and his colleagues found that if they dissected only lymph nodes that lit up with the dye, no cancers would have been missed.
“Indocyanine green dye gives us fast and easy visualization of lymph node pathways that does not require the use of radioisotopes or colloids,” he explained in his poster presentation (Abstract 70).
The near infrared dye fluoresces and can readily be identified during laparoscopic procedures, he said. “No cancer-positive lymph nodes were overlooked with our concept. In 60 percent of our cases, the postoperative prostate specific antigen was less than 0.01 ng/ml. The lymph node not linked to the prostate can be spared using indocyanine green dye.”
He said that using indocyanine green dye to visualize the entire prostate lymph node drainage system offers an “evolution of treatment” that may bypass the need for sentinel node biopsy procedures.
“Fluorescence-targeted lymph node dissection allows us to identify the lymphatic drainage of the prostate with great reliability, and it proved to be more precise than extended lymph node dissection in patients with intermediate- and high-grade prostate cancer.”
Used in Other Modalities
Asked for his perspective, Manish Vira, MD, Director of the Fellowship Program in Urologic Oncology at North Shore-Long Island Jewish/The Arthur Smith Institute for Urology in New Hyde Park, New York, said that at least for now, he was not aware of any studies using the dye in prostate cancer in the United States—“but that doesn't mean it is not being done here.”
Still, he noted, “there is nothing special about this particular dye. It is used in a lot of different modalities such as kidney cancer, head and neck cancer, melanoma, breast cancer, and other cancers.
“There are special cameras that can visualize the dye so that in kidney cancer, for example, the use of the dye helps visualize the vasculature so you can better assess the blood vessels that are feeding the tumor.
“What is different about this study is that the dye is being used in order to visualize the prostate lymph nodes,” he continued. “Prior to surgery, the dye is injected into the prostate with the idea that the dye would then follow the lymph node drainage of the prostate. The dye is injected first. During the prostatectomy the dye has time to flow through the lymph node drainage system.”
He said the goal of the treatment would be to provide a more targeted lymph node dissection and perhaps be able to limit the extent of the dissection—“That would result in a higher rate of finding positive lymph nodes.”
The Austrian research team reported on 38 consecutive cases involving men who presented with intermediate- and high-risk prostate cancer who were treated with laparoscopic radical prostatectomy with lymph node dissection.
Hruby explained that during the procedure, two milliliters of indocyanine green were injected transperineally into each lobe under transrectal ultrasound guidance. The use of transperitoneal injection of the dye was accomplished without any periprostatic extravasation. “Perineal access allows for precise injection on indocyanine green dye without compromising the intraoperative view, and also reduces the risk of infection.”
After removal of the complete indocyanine green-visualized lymph node template on each side, a standard extended prostate lymph node dissection was added as a trial control measure. All lymph nodes were evaluated by 250 micrometer sections and immunohistochemistry.
Fluorescence-positive stained nodes were found on both sides in all patients except one. In total, 596 nodes—or about 17.9 nodes for each patient—were removed. Of those, 473 nodes—or 14.3 nodes per patient—were fluorescently stained. Metastases were observed in 15 patients. Two of those patients had solitary micrometastases, and another three patients were found to have lymph nodes that contained tumor cell clusters.
“No non-stained metastases were found in addition to fluorescent-positive metastases,” Hruby reported. The researchers also discovered five metastases that were outside of the extended prostate lymph node template.
Vira noted that because in two of those five patients, the postoperative PSA levels were 3.1 and 8.9 ng/ml, “that tells us that those patients likely have systemic prostate disease and that the lymph node dissection probably had no real impact on outcomes.
‘To Take to Next Level’
“This is an interesting study,” Hruby continued. “I think the use of indocyanine dye shows some promise. But to take this to the next level, we need to know if you can use the dye to guide dissection of only those lymph nodes; compare those patients with others who have all the lymph nodes dissected, and then follow those patients to see which group does better and which patients do better.”
There is also another issue with the population studied, he said, and that is the high rate of patients who had lymph node involvement—“Of the 38 patients in this study, 39 percent had positive lymph nodes, and that incidence is far, far above what we see in the United States. In these high-risk patients, if we see 10 percent of patients undergoing surgery with positive lymph nodes, that would be a big number. This patient population may be different from what we see in the United States.”
Vira said that high rates of positive lymph nodes are often characteristic of prostate cancer studies in Europe: “It is higher in Europe than in the United States and that may be due to the prevalence of screening here. We just don't see that high a rate. We are just seeing patients with less cancer than in Europe. The Europeans are seeing patients with more advanced disease, and that's why 40 percent of those patients will have positive lymph nodes.
“If I look at all my patients with prostate disease, the lymph node positivity is probably less than five percent,” he continued. “Even if you take the high-risk patients, at worst the rate of positive lymph nodes observed is in the range of 10 to 15 percent even though we are doing extended lymph node dissections and everything else.”