Yang (John) Qiao, Texas A&M University College of Medicine, 2019

Editor: Justin Foster, MD, PGY-4 Rochester Regional Health, Rochester, NY

Renal cell carcinoma (RCC) is an oncologic disease originating from the cells lining the small tubes of the kidney, the functional filtration organs of the body.  Symptoms of RCC can manifest in a classic triad of hematuria, flank pain, and a palpable abdominal mass.  Treatment options for RCC are stratified according to the TNM cancer staging categories.  Although surgical partial nephrectomy has traditionally been the standard-of-care for RCC, the American Urologic Association (AUA) 2017 Guidelines were updated to include percutaneous ablation (i.e. cryoablation, radiofrequency ablation) and active surveillance as additionally acceptable treatment options for patients with stage T1a RCC (solitary tumor  ≤4 cm, fully contained within the kidney).  Furthermore, it is hypothesized that different subtypes of RCC (i.e. clear cell vs. papillary) exhibit variable percutaneous ablation susceptibilities.

In this study, a retrospective review of a single institution’s RCC ablation registry was analyzed to investigate the efficacy of percutaneous cryoablation (PCA) on patients with T1a clear-cell RCC (ccRCC) vs. papillary RCC (pRCC) [1].

Study Population:

Following institutional review board approval, a retrospective review of a single institution’s renal ablation registry was performed to identify 173 patients with biopsy-proven stage T1a RCC who received PCA between January 1st, 2003 and December 31st, 2015.  ccRCC vs. pRCC subtype determination was performed either prior to the procedure or intra-operatively during PCA.  Patients with multiple tumors, previous history of RCC, genetic syndromes associated with RCC, and less than 3 months of post-operative follow-up were excluded from the study.  In addition, patients with RCC subtypes other than ccRCC and pRCC were also excluded from the study due to the small sample size.

Treatment Protocol:

Patients were preferentially treated with large-caliber PCA probes (2.4 mm) (cryoablation overview: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3976170/ [2]) and all were treated under general anesthesia using a combination of ultrasound (US) and computed-tomography (CT) guidance (ultrasound overview: https://jintensivecare.biomedcentral.com/articles/10.1186/s40560-016-0173-0 [3]; CT overview: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1123029/ [4]).  RCC tumors were treated with a first cycle of conventional freeze/passive thaw and a second cycle of re-freeze/active thaw.  Duration of freeze cycles were based on extension of ice ball 3 – 5 mm beyond tumor margin.  Contrast-enhanced CT or MRI were performed 24-hours post-op to ensure technical success of the procedure as defined by an ablative zone completely encompassing the previous tumor margin.

Data Collection and Statistics:

Subsequent clinical follow-up and patient imaging using contrast-enhanced CT and MRI was performed at 3, 6, and 12 months following PCA, and yearly thereafter for evaluation of local tumor recurrence, new renal tumors, metastasis, and changes in serum creatinine levels.  Patient demographic data comparing age, tumor size, and nephrometry score for ccRCC (130 patients) vs. pRCC (43 patients) was performed using a paired t-test.  Survival outcomes over time were plotted using Kaplan-Meier curves.  P-values < 0.05 were considered statistically significant.

Results and Outcomes:

Technical success of PCA was achieved in all patients with RCC.  Local tumor recurrence developed in 6 patients with ccRCC at a median period of 24 months post-op, and 0 patients with pRCC.  Although these findings are consistent with previous studies of both PCA and radiofrequency ablation, which demonstrated a greater recurrence rate among patients with ccRCC compared with pRCC, the differences in this study were not found to be statistically significant (P = 0.34).  5-year disease-free survival rates for ccRCC vs. pRCC patients treated PCA were 88% and 100%, respectively, but were also not statistically significant (P = 0.11).  Furthermore, none of the patient deaths during the follow-up period were attributable to RCC.  Major complications were seen in 5.2% of PCA patients, including perinephric hemorrhage requiring angiography and embolization, and urine leak immediately post-op treated with ureteral stenting.  There was no median change in creatinine level at 35 months post-op follow-up.

Conclusion:

PCA is a reasonable minimally-invasive treatment option for patients with stage T1a RCC, providing favorable oncologic and safety outcomes compared to surgical and surveillance approaches.  Although no statistically-significant difference was found in tumor recurrence rates in this study among PCA-treated ccRCC vs. pRCC, percutaneous tumor biopsy may still be a valuable diagnostic consideration for distinguishing between these two subtypes in treatment guidance of stage T1a RCC, due to recurrence rate differences found in previous other studies [5 – 7].  In this study, the improvement in recurrence rates may be attributable to either the use of general anesthesia, a small sample size, or a combination of both.  The major complication rate of PCA vs. open partial nephrectomy vs. laparoscopic partial nephrectomy was favorable at 5.2% vs. 6.3% vs. 9.2%, respectively; and may be further minimized via prophylactic pre-ablative embolization of hypervascular lesions, and ureteral stenting for patients with tumors located in close proximity to the renal pelvis.  Lastly, the median length of stay (LOS) in the hospital for patients treated with PCA (1 night) was a large improvement over the LOS of even the most minimally-invasive surgical approach– robot-assisted partial nephrectomy (2.5 – 6.5 nights).  In conclusion, this study adds further evidence for the advancement of PCA as a standard-of-care treatment option for stage T1a RCC due to its equivalent efficacy and minimal number of side-effects compared with surgery.  In addition, further studies with larger sample sizes are needed to significantly differentiate the efficacy of PCA therapy between ccRCC vs. pRCC subtypes.

References:

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2. Baust J, Gage A, Johansen TB, Baust J. Mechanisms of cryoablation: Clinical consequences on malignant tumors. Cryobiology. 2014;68(1):1-11. doi:10.1016/j.cryobiol.2013.11.001.

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4. Garvey CJ, Hanlon R. Computed tomography in clinical practice. BMJ. 2002;324(7345):1077-1080. doi:10.1136/bmj.324.7345.1077.

5. Iannuccilli JD, Dupuy DE, Beland MD, Machan JT, Golijanin DJ, Mayo-Smith WW. Effectiveness and safety of computed tomography-guided radiofrequency ablation of renal cancer: a 14-year single institution experience in 203 patients. European Radiology. 2015;26(6):1656-1664. doi:10.1007/s00330-015-4006-7

6. Lay AH, Faddegon S, Olweny EO, et al. Oncologic Efficacy of Radio Frequency Ablation for Small Renal Masses: Clear Cell vs Papillary Subtype. The Journal of Urology. 2015;194(3):653-657. doi:10.1016/j.juro.2015.03.115

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