Adoption of robot-assisted radical nephroureterectomy permits a minimally invasive option for management of upper tract urothelial carcinoma in geriatric patients: comparison with non-geriatric patients with intermediate-term oncologic follow-up

Upper-tract urothelial carcinoma remains a highly aggressive urological malignancy especially in elderly population [3, 5]. The management of non-metastatic, UTUC necessitates counseling based on individual and cancer-specific factors. The standard of care option chosen by many of these patients is radical nephroureterectomy; however, some patients have historically been disqualified from this major operation based on age. Significant disease-related morbidity such as renal obstruction, infected hydronephrosis, flank pain, and hematuria often factor into surgical decision-making for patients with UTUC. Given high acuity of symptomatology these patients are not suitable for neo-adjuvant chemotherapy and require consideration of surgical intervention. With improvement in surgical approaches, RARNU may be an option for older and more frail patients with similar outcomes and rates of complications relative to younger, healthier patients. The perioperative benefits of RARNU compared to open or laparoscopic approaches have been documented and large population-based studies have demonstrated equivalent oncologic outcomes [18, 23]. Our study results suggest that the decision to operate on geriatric patients with UTUC, by means of RARNU, was not associated with increased risk of disease recurrence or 30-day perioperative complications when compared to operating on younger patients with UTUC.

Several study groups have reported on the oncologic outcomes in patients that chose to pursue RARNU, and their results are like those reported in our study. Compared to a subset of 252 patients undergoing RARNU with a median age of 70 years, oncologic outcomes were similar in patients ≥ 75 years in our study [15]. Grossman et al. found a BRFS of 58.9%, RFS of 72.9%, CSS of 85.5%, and OS of 80.9% at three years [15]. Bae et al. found a 3-year BRFS of 70% and OS of 92% in their cohort of 119 patients with a median age of 69 years and Clements et al. found 3-year OS of 67% for 315 patients from a Medicare database [23, 24]. The 3-year BRFS in our geriatric cohort (67%) was comparable or improved compared to those previously reported with lower RFS and OS. An improved BRFS in our geriatric cohort is likely directly related to worse OS. Bladder recurrences occur commonly in patients with UTUC; however, patients with a lower life expectancy may not live long enough to experience a bladder recurrence. Age has been reported as an independent predictor of worse CSS and OS after RNU and the elderly cohort in this study has the highest median age reported thus far in the literature [10,11,12] Furthermore, upstaging to muscle invasive UTUC in our cohort was 48% in our cohort which is higher than the previously reported 41.7% and may contribute to the lower RFS.

Oncologic outcomes for geriatric patients pursuing RARNU may continue to improve with the implementation of neoadjuvant (NAC), adjuvant chemotherapy (AC), and multidisciplinary evaluation including geriatric evaluation to provide best medical optimization. Evidence from a 2020 systematic review and meta-analysis by Leow et al. detailed the OS and CSS benefit of NAC and AC compared to RNU alone [25]. Furthermore, in a multi-center, retrospective cohort study of elderly (> 68 years) versus non-elderly patients receiving NAC with RNU, there was no difference shown for RFS or CSS, suggesting that older patients may also benefit from NAC [26]. Most patients in our cohort were treated with RARNU prior to the general acceptance of NAC for UTUC, and thus survival estimates may improve with the implementation of NAC.

The decision to offer major surgery to elderly patients has traditionally been thought to warrant counseling on higher rates of post-operative complications than younger patients, though more recent studies have demonstrated equivalent post-operative complication rates [27, 28]. In our study, older patients had a higher median ASA status and lower BMI; however, major and minor perioperative complications rates were not increased relative to the younger patient cohort. Furthermore, our geriatric cohort had a similar frequency of minor and major C.D. complications to those reported in Veccia et al. (14% vs 18%, minor and 0 vs 3%, major) [18]. The frequency of overall 30-day complications in our geriatric cohort was lower than that previously reported. These differences may be attributed to improvement in surgical technique, preoperative optimization, or frailty of geriatric cohort as frailty has been demonstrated to have a strong correlation with post-operative complications [29]. The local protocol at our institution includes pre-operative risk stratification and optimization by both Internal Medicine and Anesthesiology to identify co-morbidities that need to be addressed prior to surgery.

This study has few limitations. First, the study is limited by its retrospective design and the inherent biases associated with it. Next, there is a significant selection bias due to most patients choosing to undergo an operation by our center’s high-volume robotic surgeon that is well versed in RARNU techniques. Thus, results of our study are limited in generalizability particularly to patient outcomes when in the hands of urologists that do not routinely manage UTUC or perform RARNU. Second, our prospectively maintained, nephroureterectomy database has significant heterogeneity regarding the perioperative and postoperative management and surveillance that changed as newer literature emerged, and thus oncologic outcomes may be expected to improve. Finally, our study did not implement a frailty score. Compared to ASA status, frailty scores may better predict perioperative complications and as such, future studies may benefit from the inclusion of comorbidity indices.

Nonetheless, this study includes a patient cohort with a higher median age than any previously reported, to the best of our knowledge. Understanding the role of surgery in patients with malignancy, such as UTUC, is critical due to growing prevalence of UTUC in the aging population. Our study highlights that the choice to perform surgery in this case with RARNU on patients ≥ 75 years with non-metastatic UTUC was not associated with increased risks of oncologic disease recurrence or post-operative complications. The differences in OS were in line with prior studies, thus validating the importance in counseling patients of advanced age regarding preoperative optimization and proper patient selection [14]. Advances in surgical techniques for RARNU, such as complete retroperitoneal access and use of single-port system, as well as the use of NAC, may improve oncologic parameters and decrease perioperative complications in this age group; however, further studies are needed [16].

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