[NEOADJUVANT CHEMOTHERAPY BEFORE RADICAL CYSTECTOMY - MIGHT IT BE OFFERED SELECTIVELY?]

INTRODUCTION: Neoadjuvant cisplatin-based chemotherapy prior radical cystectomy is the standard of care in patients with a muscle invasive bladder cancer. It is intended to treat micro-metastases. However, most patients do not develop metastases even without chemotherapy and are receiving this treatment in vain. In this study, we looked for pre-operative risk factors for developing metastases that can triage the patients that really need neoadjuvant therapy. METHODS: From 1998 to 2018, 285 patients underwent radical cystectomy without neoadjuvant chemotherapy. During a median follow-up of 42.5 months, 99 patients (34%) developed recurrent disease after a median duration of 12 months. The study compared 10 different preoperative parameters of patients who developed or did not develop recurrence. RESULTS: An increased risk of metastases was found in older patients (39.8% in older than 69 years vs. 33.3% in younger patients, p=0.045), in patients with a high Charlson Comorbidity index (46.2% in 5 and above vs. 28.2% when lower than 4, p=0.003), and in patients with large tumor diameter (p=0.01). No difference was found in the other variables examined including: gender, primary versus secondary tumor, tumor stage, presence of histological variant, hydronephrosis, carcinoma in situ (CIS) or sarcomatoid differentiation. CONCLUSIONS: Older age, comorbidity, and large tumor diameter predict the risk of recurrence after radical cystectomy. However, overlap between the groups precludes the use of these parameters for clinical decisions. Therefore, neoadjuvant chemotherapy treatment should currently be offered to all candidates for radical cystectomy. Hopefully, future molecular markers will be able to predict the risk of metastases.

Trimodal therapy in T2-4aN0M0 bladder cancer--How to select the best candidate?

The reported results of trimodal treatment (TMT) in muscle-invasive bladder cancer vary widely. We attempted to characterize the profile of ideal candidates for this approach. Between 2000 and 2019, 105 patients (median age 78 years) with T2-4aN0M0 bladder cancer were treated with TMT and analyzed retrospectively. Mean radiotherapy dose was 62 Gy (SD 8.4). Ten pretreatment prognostic parameters were evaluated including tumor diameter on pre-TURBT CT. Multivariate analyses was performed and combination of parameters was studied. After a median follow-up of 29 months, 53 patients (50.5%) developed recurrence and 70 patients (67.7%) died. Death was disease-specific in 46 patients (65.7%). Tumor diameter was the most significant prognostic parameter with p < 0.0001 for overall, disease-specific and recurrence-free survivals. For every 1 cm increase in tumor diameter, the risk of disease-specific mortality increased by 1.57. Age, cisplatin eligibility and the Charlson Comorbidity Index were significant predictors of overall survival but not of disease-specific or recurrence-free survival. Patients who were cisplatin-eligible with a tumor diameter ≤3 cm had a 5-year disease-specific survival rate of 79.2% as opposed to 33.9% in patients without one of these features (p < 0.001). When tumor diameter exceeded 5 cm (irrelevant of all other parameters), 5-year disease-specific survival rate was only 28.2%. Patient profiles can accurately predict response to TMT. In cisplatin-eligible patients with a tumor diameter ≤3 cm, TMT provides an excellent disease-specific survival rate. In patients with a tumor diameter >5 cm TMT renders unacceptably poor treatment outcomes.