Several studies have established an association between DM and an increased cancer incidence and poorer prognosis across various malignancies, including colorectal, breast, endometrial, liver, pancreatic, and BC [4–8]. The precise nature of this association remains under investigation. While some propose a direct causal relationship mediated by hyperinsulinemia and poor glycemic control [16], others suggest an indirect association driven by shared risk factors, among which one of the principal ones is obesity [17].
The crucial role that DM might play in worsening survival outcomes was initially debated about twenty years ago, when Coughlin et al. performed a prospective study, evaluating one million of American patients for a long-time period of 16 years, and identified DM as an independent risk factor for cancer specific mortality (CSM) in men (RR 1.43, 95% CI 1.14–1.80) [18]. Similar findings were reported by Campbell et al., in a study with a median follow up of 26 years, showing that the risk of death in DM male patients with BC was superior (RR 1.22, 95% CI 1.01–1.47) [19].
In addition, such association between DM and BC was highlighted in another multi-center study, in which the authors observed a positive correlation between DM and BC mortality, with higher fasting blood glucose levels associated with a greater risk of death [20]. Moreover, Zhu et al, in a cumulative meta-analysis, displayed a negative impact on BC mortality in DM men patients (RR 1.55, 95% CI 1.30–1.82) but also in DM female ones (RR 1.50, 95% CI 1.05–2.14) [21].
In the last decade, evidence supporting a negative impact of DM on oncologic outcomes in patients undergoing extirpative surgery for BC have been accumulating, with several data deriving from large cohorts studies. Accordingly, in a more recent meta-analysis, Xu et al. included and analyzed 21 cohorts studies, involving 13 millions participants, and reported that DM was associated with a higher risk of BC and cancer mortality (HR: 1.23; 95% CI 1.12–1.35) [8] .
These results are in agreement with a systematic review conducted by Cantiello et al., where the effects of various comorbidities, such as smoking status, hypertension, obesity, and DM, on oncologic outcomes of BC were analyzed and well-established [5].
All the literature examining the relationship between DM and BC often refer to series in which patients were treated through an open approach, thus before the wide-spread diffusion and consequent adoption of robotic surgery for BC.
As a matter of fact, although the open approach was the most widely adopted worldwide for several years, RARC has gained increasing popularity over the past decade. This is due to the potential benefits of a minimally invasive approach, such as lower morbidity, shorter hospital stays (LOS), and quicker patient recovery. The oncological effectiveness of RARC has been extensively studied, and its equivalence to ORC has been confirmed in recent randomized controlled trials (RCTs) [22–26]. In addition, long-term survival data of RARC have been adequately addressed in high-volume multicenter series, providing survival rates aligned with the largest open series [27].
Accordingly, a recent single center retrospective study including RARC-ICUD patients, reported long-term oncologic data, reinforcing the oncologic effectiveness of robotic approach (5-yr DFS 66.5%, 5-ys CSS 65.4%, 5-yr OS 61.5%) [28].
Having established the equivalence in terms of oncologic outcomes between the surgical approaches, our study investigated the impact of diabetes mellitus (DM) on oncological outcomes in patients with muscle-invasive or high-risk non-muscle invasive bladder cancer (BC) undergoing RARC.
By analyzing our results, patients with DM had demonstrated to have worse oncologic outcomes, showing a 5-yr DFS significantly lower than patients without DM (44.6% vs 63.3%, log-rank p = 0.007). DM cohort displayed also significantly lower 5-yr CSS (45.1% vs 70.1%, log-rank p = 0.001) and 5-yr OS (39.9% vs 63.8%, log-rank p = 0.001). In corroboration of these findings, at Cox- regression MV analysis, DM has been shown to be a significant predictor of CSS, providing a 2.1-fold increased risk of cancer-related mortality (HR = 2.1, 95% CI 1.35–3.24, p = 0.001), and OS, providing a 2.05-fold increased risk of all-cause mortality (HR = 2.05, 95% CI 1.43–2.96, p < 0.001). The present paper is not devoid of limitations. Firstly, its retrospective design and a relatively small cohort, particularly regarding patients with DM, restrict our ability to analyze potentially significant factors like lymphovascular invasion, mixed histologic variants, and medication use (aspirin, statins). Secondly, the unassessed duration of DM introduces potential recall bias and the possibility of undetected cases. Thirdly, we did not analyze the potential differences in outcomes between DM patients receiving metformin and those not receiving it. Finally, the high-volume caseload of the centers and the need for advanced robotic surgical expertise [29] might affect the reproducibility of these outcomes in daily practice.
Despite these limitations, our study contributes valuable insights to the limited existing literature exploring the association between DM and oncological outcomes in BC patients undergoing RARC. These findings may guide future research and clinical practice for managing urothelial carcinoma patients with DM in the era of robotic surgery.