1. Should we cut the tumor?
2. What should we cut?
3. What do we do with the patient after the cut?
4. Why do we cut?
Starting with the initial question, there continues to be a lack of clarity whether patients with low grade or benign lesions such as oncocytomas or AMLs should undergo surgery. Richard et al. analyzed this question in 95 patients with oncocytoma or chromophobe RCC. With a median follow-up of 34 months, they found no progression to metastases. However, 75% of these masses grew. It remains unclear when to trigger surgical intervention. Nonetheless, this is much-needed evidence that initial surveillance of oncocytic neoplasms is safe. This is an excellent article to cite in patient counseling.
Angiomyolipomas (AMLs) are another renal mass dilemma. Bhatt et al. studied 447 patients with over 580 AMLs to better understand how these lesions act. Over a median f/u of 43 months, >92% had no growth whatsoever. The data suggest that AMLs >4cm do not require early intervention based on size alone. Again, initial surveillance clearly appears to be a reasonable way to follow these patients.
Active surveillance is increasingly becoming an important strategy in small renal masses (SRMs). Patel et al. and the collaborators of the DSSRM registry continue to produce important insights into how these patients fare. They published their findings on the very important “mental component” of how patients psychologically deal with surveillance. They found that patients have the same mental component scores regardless if they chose surveillance or treatment for their SRM. This is great news, as it is initial evidence that patients appear to be doing well psychologically while under active surveillance for SRMs.
Switching to metastatic RCC (mRCC), Rini et al. performed a Phase 2 trial of active surveillance in mRCC patients with asymptomatic disease. 48 patients were followed for a median length of surveillance of 15 months. The trade-offs of surveillance in metastatic patients need to be better understood, but this study shows us that some treatment naive oligometastatic patients can be safely surveilled for >1 year. Grassi et al. evaluated 276 patients from 11 centers with pancreatic RCC metastases. Following metastasectomy, 5yr OS was 75%. Indeed, they found improved survival for patients who received systemic and local treatment vs. systemic treatment alone. Surveillance and/or local treatment appear to be reasonable approaches in low-volume metastatic disease. More data in this space is desperately needed to help guide management in this setting.
Dr. Kutikov specifically highlighted a randomized controlled trial by Gomez et al. in Stage IV NSCLC (lung cancer) patients with <3 metastases after 1st line treatment. Patients were randomized to local treatment (XRT or resection of all lesions) with or without maintenance therapy vs. those who received maintenance therapy alone. Amazingly, the study was terminated early because progression-free survival was so dramatically better for those receiving local treatment (11.9 mos vs. 3.9 months). It will be fascinating to see if similar data can be found in renal cancer with low-volume metastatic disease!
Question #2: What should we cut?
Shah et al. analyzed the outcomes of >1200 patients from 4 high volume centers who underwent partial nephrectomy. 7.8% had positive margins. They showed that both local and distant recurrence rates were higher in the positive margin cohort of patients. Specifically, patients with high risk tumors and positive margins had the worst recurrence rates. Surgeons should take special note of this paper, and be sure to choose wisely regarding surgical approach for high risk tumors.
Two interesting papers by Tourojman et al. and Zhang et al. both showed that preoperative proteinuria predicts overall survival in patients undergoing renal surgery. This begs the question, is the detection of proteinuria an actionable clinical variable in the decision to perform partial vs. radical nephrectomy? Hopefully, a collaboration between the fields of Nephrology and Urology may help delineate the best decision-making process when confronted with a patient (which occurs quite commonly) with preoperative proteinuria.
A series of well-analyzed and influential papers from the Mayo clinic by Gershman et al. were published this year that more definitively answered whether a lymphadenectomy is necessary during radical nephrectomy. They showed that, indeed, patients undergoing nephrectomy who have a positive lymph node have a dismal median time to metastasis of 4.2 months. However, 15% of them are still alive at 10yrs! Overall, they demonstrated that there is no survival advantage to LND in neither localized nor cytoreductive nephrectomy patients. Lymph node dissection is a highly variable procedure during radical nephrectomy, and this might help assuage fears that inadequate LND is causing patient harm.
Question #3: What do we do after the cut?
Dr. Allaf presented the work on adjuvant therapies after high-risk nephrectomy. This is a developing story and there are still many chapters to write with regard to perioperative systemic therapy.
Question #4: Why do we cut?
Lastly, Dr. Kutikov presented the pinnacle work by Hollingsworth et al. who historically showed the disconnect in RCC management. Even though treatment numbers continue to increase and diagnoses are occurring at earlier stages, mortality for RCC continues to rise. Smaldone et al. used a tumor registry to adjust for missing data and incidence and showed that the disconnect is not so clear cut. Indeed, they demonstrated that using the appropriate model, the mortality over incidence ratio is actually going down. Perhaps we actually are making an impact in this disease!
It has been a fascinating year for renal cancer, and many new avenues of research continue to open up as we move forward.
Presented By: Alexander Kutikov, M.D.
Institution: Fox Chase Cancer Center
Written By: Shreyas Joshi, MD, Fox Chase Cancer Center, Philadelphia, PA
at the 2017 AUA Annual Meeting - May 12 - 16, 2017 – Boston, Massachusetts, USA