Index Case: 75-year-old man with incidentally found 7 cm enhancing renal mass. KPS 80 – good functional status. Comorbidities: Hypertension, Diabetes.
PRO: Marc Smaldone, MD from Fox Chase notes that this patient would be considered Index Patient 4 (Major comorbidities, increased surgical risk, cT1b) in the AUA guidelines, and for these patients, all options (radical nephrectomy, partial nephrectomy, or AS are options). He accepts that while AS is not the preferred option, it is an option.
AS – an initial period of AS is safe with intermediate follow-up, applicable to healthy patients who wish to avoid intervention, and there is data to support low rates of progression and metastases.
Renal masses have varied growth kinetics. Patients with fast growth kinetics may not benefit from any intervention. Patients with slow growth kinetics are optimal candidates for cure with surgery. It is the patient with very slow or non-progressive kinetics that may not require treatment at all – but how do we identify them? “Decision to treat should be based on malignant potential, risks of therapy, patient preference, and competing risks to mortality.”
The Fox Chase group has previously created nomograms, that based on patient and tumor factors, can help stratify both RCC and non-RCC related mortality, and may help make a decision based on patient life expectancy.
NSQIP data can be used to help identify procedural risk – “should the high-risk patient have surgery” rather than “what type of surgery should they have.”
Looking at oncologic outcomes – a summary slide of all AS series demonstrates a 4-65% rate of progression to intervention. But, the rate of metastases (0-7.7%) is very low … and there is a large discrepancy between CSS and OS, indicating that even if the disease progresses, patients can live a long time.
Fox Chase’s experience with LRM (large renal masses) was varied – linear growth rate (LGR) ranged from no growth (<1 mm/year) in 36% to high LGR (>10 mm/year) in 9%. However, most had no growth or low LGR.
Similarly, Mues et al. (albeit in a small cohort of 36 patients) had a 13.8% AS failure rate (5.6% progression to mets, 8.2% delayed intervention). Even in this cohort of sick patients with large tumors and rapid growth kinetics (LGR 0.57 cm/year), there was a low progression rate and low delayed intervention rate.
Mehrazin et al. focused on the Fox Chase AS series. 68 patients had masses > 4 cm. Median LGR 0.44 cm/year. 34% had delayed intervention and none progressed to metastatic disease. There was no correlation between maximal tumor diameter (MTD) and LGR.
However, in a systematic review of AS for SRM by Smaldone, they did find that tumors progressing to metastases were larger and had faster growth kinetics. Triggers for intervention: Rapid LGR, patient preference, and health status improvement. However, there is currently no consensus.
Therefore, cT1b/T2 tumors require more definitive clinical information to drive treatment decisions and clinician tolerance for a more rapid LGR. He also notes this would be a good patient for renal tumor biopsy – if benign pathology or low-grade pathology, would support period of AS.
The decision to start with AS is not permanent or binding!
CON: R. Houston Thompson, MD presented the Mayo Clinic view of AS – don’t! They don’t survey patients with large renal masses.
First, he highlighted the MSKCC/Mayo clinic study that looked at the rate of malignancy based on size of tumor – 7 cm tumors had a 90%+ chance of being a malignancy. More importantly, they had a 60%+ chance of being high-grade. They also had a 17% chance of having metastases at the time of diagnosis. They had a very high metastatic potential. Even when treated, patients who had 7 cm masses initially, had a 67.3% recurrence-free survival at 3 years… and a 77% cancer-specific survival at 3 years.
He notes that Mehrazin et al. Fox Chase AS experience for large renal masses was actually in patients with significant competing risks of mortality – very sick patients. That does not represent the index patient! In the follow-up, McIntosh et al. Fox Chase paper (in press, EU), while the risk of death was not significantly higher in the AS group for large renal masses, the HR was still 1.6 – so it is still clinically signicant, but just may not have reached statistical significance.
Lastly, he notes that even in Smaldone’s review paper on AS in Nature Reviews: Urology, “all lesions that have progressed to metastases have been > 3 cm and have demonstrated positive growth rates over time” – which this patient clearly has! Surgical management is the gold standard.
Pro: Marc Smaldone, MD, Fox Chase Cancer Center
Con: R. Houston Thompson, MD, Mayo Clinic
Read the Second Debate: Tumor Enucleation for Sporadic T1 RCC is Oncologically Sound
Read the Third Debate:Adjuvant Therapy for High Risk RCC Should Be Used
Read the Fourth Debate:10 years of Big Data Have Changed Renal Cell Carcinoma Management
Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, | twitter: @tchandra_uromd at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA