NEPHSPARE PRO: Clinical and patient-reported outcomes after nephron-sparing treatment of small renal cell carcinoma

Background
Partial nephrectomy (PN) has traditionally been the preferred nephron-sparing treatment for small renal cell carcinoma (RCC). Cryoablation is an ablation therapy that was introduced 20 years ago as a treatment option for RCC patients with a high risk of surgical complications. Previously, this group of patients had no available treatment options. Cryoablation is a minimally invasive
procedure and is currently offered as a curative treatment, including in patients without severe comorbidity. Data from retrospective studies suggest that patients with RCC have a lower quality of life (QoL) than patients with other types of cancer, and that treatment choice and the existence of post-treatment healthy renal tissue correlate with QoL. An understanding of patient perspective is crucial for delivering the highest quality of care in the healthcare system. To be leaders in cancer treatment, we must address both clinical outcomes and patient perspective. Exploring QoL through patient-reported outcomes is one way of exploring patient perspective.


ObjectivesThe overall aim of this thesis was to assess and compare patients’ clinical outcomes and healthreported quality of life (HRQoL) after PN or percutaneous cryoablation (PCA) of RCC stage T1.

The objectives were: 1) To investigate QoL after nephron-sparing treatment of RCC stage T1, and to investigate differences between nephron-sparing treatment with regards to QoL and complications by exploring existing evidence in the published literature.  2) a: To compare patient and tumor characteristics and to describe treatment characteristics of PN and PCA for RCC stage cT1. b: To assess and compare complications and readmission rates after PN or PCA for RCC stage cT1.  3) To assess and compare short-term HRQoL and self-reported health status after PN or PCA of RCC stage cT1.

MethodsIn Study 1, we conducted a systematic review to identify studies investigating QoL and complications following nephron-sparing treatment of RCC stage T1. Study 1 was based on a systematic search of six databases. We conducted a narrative synthesis of the studies included. 

Study 2 and Study 3 were based on patients enrolled in prospective comparative cohort studies. We included patients with histologically verified primary RCC stage cT1N0M0 who were treated with either PN or PCA at Odense University Hospital or Zealand University Hospital. We included consecutively treated patients between June 2019 and February 2021. Patients were allocated to treatment according to standard clinical practice.

In Study 2, we recorded complications within 30 and 90 days of treatment, graded according to the Clavien-Dindo classification. We defined major complications as complications ³ grade 3. Furthermore, readmission within 30 days was recorded.  

In Study 3, we collected data on HRQoL using the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC). The EORTC was distributed before treatment and at 14 and 90 days postoperatively.

ResultsIn Study 1, we included eight studies, the majority of which investigated QoL after PN (n=6). Three studies reported higher scores of QoL after PN when compared to radical nephrectomy (RN). One study found no difference in QoL between two PN methods, and two studies reported that QoL increased or returned to baseline at 12 months follow-up after PN. In the two studies investigating ablation therapy, one showed a gradual increase in QoL after radiofrequency ablation, and one reported that all patients recovered to baseline after cryoablation. Across studies, we found a complication rate up to 20% after PN and up to 12.5% after ablation therapy. In addition, heterogeneity in measurement tools and time of measurement in the included studies was found.

In Study 2, we included a total of 190 treatment procedures (PN=86; PCA=104). We reported complication rates of 23% within 90 days after PN and PCA, with 3% major complications after PN and 10% after PCA. We found a readmission rate of 14% after PN and 11% after PCA. In addition, we observed an association between double-J stents and overall complications after PCA within 90 days (OR 9.88 [95% CI 2.18; 44.68]). Also, a high versus a low RENAL score (OR 5.86 [95% CI 1.08; 31.81]) and endophytic location (OR 7.70 [95% CI 1.72; 34.50]) were associated with complications within 30 days after PCA. Charlson Comorbidity Index (CCI) was associated with major complications after PN (OR 2.12 [95% CI 1.05; 4.30]).

In Study 3, we included 165 patients (PN=79; PCA=86), with a reported response rate of 98% and 96% after 14 and 90 days, respectively. We found a significant difference from baseline to 14 days after treatment in several HRQoL domains, favoring PCA over PN. However, the differences were no longer evident after 90 days. Limitations of Study 2 and Study 3 were the sample size and selection bias.

ConclusionOverall, we found little evidence available on QoL after nephron-sparing treatment of RCC stage T1. Nephron-sparing treatment appears to be either superior or comparable to other treatment alternatives with regard to QoL outcomes. Further research on QoL and complications after nephron-sparing treatment of RCC stage T1 is highly recommended, preferably using validated measurement tools, rigorous study designs, and larger sample sizes.

In Study 2, we found PN and PCA to be comparable in terms of overall complications within 90 days after treatment. However, patients treated with PCA were significantly older and had higher CCI than patients treated with PN. We found that tumor complexity and double-J stent requirements were associated with complications after PCA, and that high CCI was associated with complications after PN. Furthermore, in Study 3 we found the influence of PCA on elderly and comorbid patients did not differ significantly compared to that of PN on younger and healthier patients in terms of HRQoL when assessed at 90 days follow-up.