Conflict of interest/Disclosure
The authors have no conflicts of interest to declare.
References
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Discussion
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Dr Tina W.F. Yen (Milwaukee, WI): Congratulations on a very nicely presented study using the Alberta Cancer Registry on a very rare tumor, and a very rare tumor subtype. Among the 41 cases of adrenocortical carcinoma who underwent surgical resection, you demonstrate that almost a fifth to a quarter had the oncocytic subtype, and these patients tended to have larger tumors but less frequent and limited local invasion, be earlier stage with a trend towards potentially lower rates of recurrence and a trend towards improved survival.
I have 4 questions.
First, regarding operative approach, a total of 5 patients under a laparoscopic resection, and 2 were converted to an open approach. Do you have additional information on these 5 cases? When were their surgeries performed? Were these cases radiographically concerning for adrenocortical carcinoma? What were the tumor sizes? As you know, there is data to support an increased risk for local recurrence and peritoneal spread of adrenocortical carcinoma when removed laparoscopically. In your practice, what surgical approach, open versus laparoscopic, do you perform if there is a high radiographic suspicion for adrenocortical carcinoma?
Second, I’m not sure if you showed this in your presentation, but among the 32 in the conventional ACC group who underwent resection, at least in your manuscript, you showed that 7, almost a quarter, had M1 disease at presentation. Where were the sites of distant metastases? Were these sites known preoperatively? Did any undergo resection of their distant metastases?
Third, for the overall survival analysis, you show a trend towards improved survival in the oncocytic subtype group. Beyond con- trolling for stage, did you control for any other factors? What other variables were included in your model? Was this analysis confined
to just the 41 who underwent surgical resection? Given the small sample size, you report huge confidence intervals in your manu- script. Should a multivariate analysis be performed with such a small cohort of patients?
Lastly, given the findings that demonstrate a more indolent and potentially more favorable prognosis of the oncocytic subtype, which are in line with other study results, will you consider modifying your treatment and surveillance strategies for patients with this rare subtype?
Dr Adrian Harvey: In regards to your first question, there were 5 patients that underwent a laparoscopic with 2 conversions. These patients typically had indeterminate appearing adrenal lesions on the smaller end of the spectrum. In the 3 that underwent completed laparoscopic resection, there was no intraoperative concerns noted for invasion.
In the 2 that were converted to an open procedure, one of those patients had evidence of invasion, as well as a noted tumor thrombus extending into the inferior vena cava and thus was converted very early.
The second patient with a conversion to open had a reasonable assessment of risk of adrenocortical carcinoma, but a difficult body habitus, and we felt that the liver mobilization would be technically easier laparoscopically. So we proceeded with an initial laparo- scopic procedure with a high likelihood/planned conversion to open in that patient.
You are quite right, I didn’t mention it here, but in the manu- script, there were 7 patients with metastatic disease at presenta- tion in the conventional ACC group. Again, due to the retrospective nature, it’s sometimes hard to be delineate what the thinking of the clinicians were at the time of diagnosis. Most of these patients fall
into a couple of categories. Number one, they had equivocal find- ings at the time of their surgery that subsequently turned out to prove to be metastases over the next 6 months. So given that these findings were there on initial imaging, we categorized them as having metastatic disease at their initial presentation.
The second main category would be an unclear diagnosis. An example would be there was a patient with a large pelvic mass and an adrenal mass and the patient was originally thought to have a sarcoma with metastasis to the adrenal. Upon resection, and final pathology that this is in fact was adrenal cancer with a large peri- toneal met, and this was completely resected.
Regarding resection of the metastases, an additional 2 patients, other the one I just mentioned, had liver procedures, either resection or combined resection and RFA with the goal of an R0 end state after the initial surgery.
With regards to your third question, you are quite right and that we were a bit optimistic to do a multivariate analysis on the small number of patients. What we wanted to see was because the stage was different between the oncocytic and conventional groups, if we control for stage, would there still be the suggestion of a difference, which there was. We limited ourselves to 5 variables, and the anal- ysis was done on the 67 patients including unresectable, and they included the stage oncocytic type, hormonal status, age, and gender.
For your final question whether or not this can modify treat- ment, I think it can certainly modify the discussions related to prognosis. It’s difficult to discuss modifying treatment, particularly surgical treatment, because the diagnosis of an oncocytic variant invariably occurs postoperatively. If in the future we can find some way to imaging or other tests to recognize this preoperatively, it may influence the surgeon’s likelihood of multi visceral resection or conversion to open, but at this point in time in our practice we don’t alter our treatment based on that.
Dr Christopher R. McHenry (Cleveland, OH): Dr. Harvey, your presentation was excellent. I want to address the issue of post- operative treatment. As you have indicated there is a high incidence of recurrence with adrenocortical carcinoma, and in particular local recurrence.
In light of that, patients with locally advanced disease are treated with Mitotane and may also receive radiation therapy.
What was remarkable to me is that none of the patients with the oncocytic variant of ACC developed local recurrence. So, my ques- tion is does the diagnosis affect your recommendations for Mito- tane therapy and radiation therapy, postoperatively?
Again, I enjoyed your presentation.
Dr Adrian Harvey: There was actually 1 patient in the oncocytic group that had a combined distant metastatic and local recurrence.
In terms of Mitotane therapy, 2 of our 9 patients got Mitotane postoperatively. So there was only about 20% of our oncocytic variant group got Mitotane postoperatively, and it was around 60 to 70% in our conventional group.
So we seem to already be doing that and I don’t know if that was a conscious decision based on the pattern of recurrence. But that seems to be one of the strongest differences, and the recurrence occurs less often, and is later in the oncocytic group. It remains to be seen whether or not that can be modified through the use of Mitotane. But given that number of patients have difficulty toler- ating Mitotane, particularly at the levels we would like to provide it to have an effect, it may be prudent to withhold that in oncocytic carcinoma in the future.
Dr Samuel Snyder (Harlingen, TX): I thank you for bringing this important aspect of adrenal cancer to our attention. It helps us to continue to be aggressive as we approach these tumors.
Knowing that the oncocytic tumors had a more favorable prognosis, looking back at the tumors that were declared unresectable, did you examine them to see if possibly some of them actually could have been resected or approached more aggressively?
My second question dovetails into that. The oncocytic tu- mors were treated more aggressively with multi-organ resec- tion. Could that be partially responsible for the more favorable outcomes?
Dr Adrian Harvey: In the unresectable group, it’s hard to tell which are oncocytic and which are not. But given the retrospective review, it’s hard to delineate the reasoning of the surgeon as to why these were deemed unresectable and why different ones were considered resectable. Many of them were because of presence of metastatic disease. Due to these limitations we were not able to do that first analysis.
With respect to your second question, I would be more inclined to believe that if there was evidence of pathological invasion on the final pathology report. With only 2 patients having invasion into the surrounding adipose tissue, it’s hard to imagine that multi visceral resection contributed to the improved recurrence rates and survival rates or apparent improved rates in those patients, although with that small number of patients, I certainly couldn’t say that definitively.