Ablation Therapy Versus Partial Nephrectomy for Renal Cancers

Is there a right approach to managing cT1a renal masses? In a recent publication in the Journal of Urology, researchers from Canada addressed this subject with emphasis on comparing percutaneous ablation with partial nephrectomy.¹ cT1a renal masses are defined as ≤4 cm in greatest dimension and limited to the kidney.² Currently, the gold standard approach, when amenable, is a partial nephrectomy, which has very high rates of disease-specific survival.³ In recent years, however, these small renal masses have been managed with ablation strategies and active surveillance. Indeed, a systematic review in 2016 showed similar rates of cancer-specific survival and overall survival (OS) when renal masses were managed with ablation compared to partial nephrectomy.⁴ The authors noted the strength of their evidence was low, but that past randomized controlled trials exploring use of ablation in this context had failed due to poor recruitment.

RFA and Cryoablation for cT1aN0M0

In 2019, a large single-institution study comparing partial nephrectomy, radiofrequency ablation (RFA), and cryoablation found no difference between the procedures in local recurrence rates, metastasis-free survival, or mortality.⁵ Against this background, the current study was established to “report on the largest multi-institutional comparison of ablation and partial nephrectomy for cT1a renal tumors” using the Canadian Kidney Cancer Information System (CKCis) database, a prospective national cohort collecting data on patients with any renal malignancy from 14 Canadian academic institutions.⁶

Patients included in the study underwent a partial nephrectomy or ablation with either RFA or cryoablation for cT1aN0M0 disease over a 10-year period from 2011 to 2021. Important exclusion criteria were presence of multiple renal masses, benign or missing tumor pathology, and non–renal cell carcinoma (RCC) histology. Baseline characteristics were collected, and the primary outcomes were defined as recurrence-free survival (RFS) and OS. Recurrence was defined as a new focal enhancement in the ablation or resection bed, enlargement of the ablation defect, or evidence of metastasis on imaging studies. The authors defined OS as survival until death from any cause. Importantly, follow-up imaging was at the discretion of the clinician and not protocoled. The authors analyzed the data with inverse probability of treatment weighting (IPTW) with propensity scores to mitigate against differences in baseline characteristics.

After applying the exclusion criteria, 2276 patients were enrolled in the study, 2001 of whom underwent partial nephrectomy and 275 who underwent ablation with cryoablation (n=129) or RFA (n=146). Patients in the partial nephrectomy cohort tended to be younger (60 vs 67 years) and had fewer comorbidities (Charlson Comorbidity Index [CCI], 4 vs 5). No significant differences were seen when comparing tumor size, sex, race, or smoking history. Median follow-up for patients was longer in the ablation cohort when compared with the partial nephrectomy cohort (2.6 vs 2 years). A total of 24% of patients were lost to follow-up in the partial nephrectomy cohort, compared with 21% in the ablation cohorts.

In both cohorts, a higher CCI, larger tumor size, and male sex were associated with a higher risk of recurrence. Similarly, OS was associated with a higher CCI and male sex. Univariate analysis revealed that RFS (hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.17-0.39; P< 0.001) and OS (HR, 0.46; 95% CI, 0.26- 0.81; P=0.007) significantly favored partial nephrectomy.

Kaplan-Meier curves presented by the authors indicated that the event rate for disease recurrence at 5 years was seen in 11% of patients who received ablation vs 2.5% who had a partial nephrectomy. Similarly, death from any cause at 5 years was seen in 5.8% versus 2.1% in the ablation versus partial nephrectomy cohorts, respectively. The authors also reported that of the patients who underwent ablation therapy and had recurrence, 12 underwent surgery (3 partial nephrectomies, 9 radical nephrectomies), 13 underwent repeat ablation therapy (9 RFAs, 4 cryoablations), and 3 received systemic therapy.

Only 1 patient underwent RFA followed by a partial nephrectomy, and 4 patients underwent no further treatment. Of the patients who initially underwent a partial nephrectomy and had disease recurrence or metastases, 13 required repeat surgery alone (8 second partial nephrectomies, 5 radical nephrectomies); 5 underwent ablation (3 RFAs, 2 cryoablations); 8 underwent surgery (1 partial nephrectomy; 7 radical nephrectomies) plus systemic therapy; 1 underwent ablation followed by radical nephrectomy with subsequent systemic therapy; 20 underwent systemic therapy; and 16 had no further management.

Trial Results and Scoring

When propensity scoring with IPTW was used to compare ~1500 patients who underwent partial nephrectomy to 164 who underwent ablation therapy – RFS was significantly improved in those who underwent a partial nephrectomy compared to those who underwent ablation (adjusted HR, 0.36; 95% CI, 0.18-0.71; P=0.003), however, there was no statistically significant difference in OS between patients who underwent partial nephrectomy and those who underwent ablation therapy.

The authors commented that their large multicenter report using IPTW propensity scoring adjustments adds to the literature by informing on an important treatment-related outcome: There is an increasing number of patients who are treated for small renal masses and, although guidelines include both partial nephrectomy and ablation therapy as options, the studies that support ablation therapy are limited by tumor heterogeneity, only rare biopsy confirmation of RCC, older age of patients, and small retrospective cohorts. In contrast, in addition to using IPTW propensity scoring adjustments, the present study included a multicenter cohort with confirmed RCC, and the patients who underwent ablation therapy were younger than in many other previously published studies.

After IPTW propensity scoring adjustments, the authors found no statistically significant difference in OS between patients receiving partial nephrectomy versus ablation. A difference favoring partial nephrectomy was seen in RFS at 2 years (97.4% vs 88.1%; HR; 0.36; 95% CI, 0.18- 0.71; P=0.003). The authors concluded that “these results emphasize that although these two treatment options are offered to different patient populations, the local cancer control of partial nephrectomy is superior.”

References

1. Millan B, Breau RH, Bhindi B, et al. A comparison of percutaneous ablation therapy to partial nephrectomy for cT1a renal cancers: results from the Canadian Kidney Cancer Information System. J Urol. 2022;208(4):804-812. doi: 10.1097/JU.0000000000002798
2. National Comprehensive Cancer Network®. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Kidney Cancer. Version 3.2023. Published September 22, 2022. Accessed September 30, 2022. https://www.nccn.org/professionals/physician_gls/pdf/kidney.pdf
3. Lavallée LT, Tanguay S, Jewett MA, et al. Surgical management of stage T1 renal tumours at Canadian academic centres [published correction appears in Can Urol Assoc J. 2016;10 (7-8): E281]. Can Urol Assoc J. 2015;9(3-4):99-106.
4. Pierorazio PM, Johnson MH, Patel HD, et al. Management of renal masses and localized renal cancer: systematic review and meta-analysis. J Urol. 2016;196(4):989-999. doi: 10.1016/j.juro.2016.04.081
5. Andrews JR, Atwell T, Schmit G, et al. Oncologic outcomes following partial nephrectomy and percutaneous ablation for cT1 renal masses. Eur Urol. 2019;76(2):244-251. DOI: 10.1016/j.eururo.2019.04.026
6. Tajzler C, Tanguay S, Mallick R, et al. Determining generalizability of the Canadian Kidney Cancer information system (CKCis) to the entire Canadian kidney cancer population. Can Urol Assoc J. 2020;14(10): E499-E506. doi: 10.5489/cuaj.6716