Practice Update | Onology

ASCO 2017 17

Extent of lymph node dissection in prostatectomy: an update Interview with Thomas J Guzzo MD, MPH Dr Farzanna Haffizulla speaks with Dr Guzzo, Assistant Professor of Urology and Surgery at the University of Dr Haffizulla: I wanted to talk about the group from Sao Paulo conducting the phase 3 trial comparing limited and extended lymphadenectomy in prostate cancer. Can you tell us how the results of this particular study can affect clinical practice? Dr Guzzo : Sure. There is a lot of question as to what the extent of lymph node dissection should be in a variety of cancers. In urology, we debate all the time what the extent of a lymph node dissection should be in both bladder cancer and prostate cancer, and there’s a lot of retrospective data that says the more lymph nodes that you take out the potentially better the patient’s going to do, not only from knowing their stage standpoint but potentially from an onco- logic standpoint as well. This group actually did a prospective study, a phase 3 randomized trial including patients with intermediate and high-risk prostate can- cer, and they randomized them to a standard limited pelvic lymph node dissection that you would expect that most prostate cancer patients would get versus an extended pelvic lymph node dis- section. And what they found was that the groups were very well matched, as youwould expect in a randomized trial, and the patients were no different pathologically. So what they found was there was no difference in the groups preoperatively with regard to clinical or pathologic features. But, as you would expect, they found 6 times the amount of metastatic disease in the extended pelvic lymph node patients because obviously, they were taking more lymph nodes out, but importantly, the oncologic outcomes weren’t the same. This is very early data and you would expect potentially with further follow-up that may change, but the oncologic outcomes were the same. I still think this is an important study because in prostate cancer we have many new therapies for patients with advanced disease and I think knowing which patients have meta- static disease early on may direct adjuvant and salvage therapies after radical prostatectomies, so still a very important study. Dr Haffizulla: What is your current clinical practice in determining who should get a limited versus an extended lymphadenectomy? DrGuzzo : I use nomograms likemost physicians do, and patients with intermediate to high-risk disease, particularly high-risk disease, I will do an extended pelvic lymph node dissection for prostate cancer. Again, I think it gives us very important staging information. The jury’s still out as to whether it changes oncologic outcomes, but I do think patients want to know where they stand from a disease standpoint. I do think it can help us make decisions postoperatively with regard to adjuvant therapies. Pennsylvania’s Perelman Center for Advanced Medicine, on limited vs extended lymphadenectomy in prostate cancer.

or not?” and I always said, “You know, probably not a lot, but I don’t know.” And now we know. Dr Haffizulla: Among high-risk patients who’ve received CAPOX as opposed to FOLFOX, there appears to be less of a difference between 3 and 6 months of therapy. Do you see this as a reason to consider the CAPOX over the FOLFOX upfront? Dr Grothey: This is one of the surprise findings that we had because we allowed investigators and patients to choose between CAPOX and FOLFOX, which CAPOX is oral capecitabine, oxaliplatin, and FOLFOX is IV 5-FU leucovorin. Not every study allowed it. The US study only allowed FOLFOX; there was no CAPOX. But there is some preference in the countries like Japan, like the UK, and even in Italy that they are leaning more toward CAPOX because it’s cheaper for society because you don’t need a port, pump, and nursing time, etc. For society, it’s cheaper to use CAPOX than FOLFOX. The surprising data were that 3 months of CAPOX tracked very favorably compared to 6 months. I mean even in higher-risk group of patients, the ones we identified before, 3 months of CAPOX seemed to be enough. The hazard-ratio estimate was 1.02. That is really as close to one as you can probably get in this subgroup analysis. For FOLFOX, it seemed to be that higher-risk patients needed longer duration of therapy, as you mentioned, but we still don’t completely understand why that is. And we don’t have a randomization, meaning a direct comparison between CAPOX and FOLFOX, so you can’t say one is better. But having said that, if patients or physicians prefer to use CAPOX, 3 months is enough. Will that influence our clinical practice? I could see, yes. It could be that physicians might have to at least offer CAPOX to patients, and then patients can decide. And I can see a lot of patients will not want to have a port placed; will not want to have surgery to put it in and take it out, and might be willing to get 4 infusions of oxaliplatin through peripheral access, and take pills at home. And then after 12 weeks be done with the adjuvant chemotherapy. It could be quite attractive, so we’ll see how this evolves over time. Dr Haffizulla: We talked about the idea of collaboration before, and I know that one of the reasons it was designed and imple- mented was because the number of patients needed to answer the important questions about adjuvant therapy to ratio was more than one group could really accrue or maintain. What are some other unanswered questions that could come from such large- scale collaborations like IDEA? Dr Grothey: First of all, we will really mine that data for the benefit of our patients. Can we identify patients beyond the stage groups that we just talked about who might need more or can get away with less treatment? The CAPOX versus FOLFOX question will also try to be analyzed with propensity analysis and sensitivity analy- sis. That’s something we are already planning to do. Then some of these studies, actually mostly of the studies have biomarkers. That’s another important point we have concurrently randomized patients in a worldwide effort to now really compare, for instance, outcome of patients with certain molecular features in Japan ver- sus the UK versus Italy, etc. We can look at lifestyle factors because these factors might be different in different countries. Genetics, pharmacogenetic and genetic predispositions might be different, so that is partly one of the future strengths that we can mine the data. We could do a lot of, what we call, exploratory analysis, which always sounds a little bit like after the fact, but it’s important to look at the whole data pool of 12,800 patients to get the best out of that. That’s for the benefit of patients in future research.

Watch the full interview on PracticeUpdate.com

Watch the full interview on PracticeUpdate.com

VOL. 1 • NO. 2 • 2017