The Role of Pelvic Lymphadenectomy in Organ-sparing Treatment of Muscule-invasive Bladder Cancer

Abstract

Although radical cystectomy (RCE) with extended pelvic lymph node dissection (ePLND) is the standard of care for patients with muscule-invasive bladder cancer (MIBC), the rate of partial cystectomy (PCE) in the world remains quite high (7%). In particular, the organ-sparing approach can be chosen when it is impossible to perform RCE due to medical contraindications or at the request of the patient. Its advantages include less trauma, better functional results, no need for neocystoplasty, and a better quality of life than after RCE. Moreover, with adequate patient selection, the five-year survival after PCE corresponds to that after RCE. The high probability of metastatic/micrometastatic lesions in regional lymph nodes (LN) at the time of detection of MIBC is the basis for a combination of CE, PLND, chemotherapy, immunotherapy, radiotherapy. However, due to the lack of randomized trials on the subject, the optimal volume of PLND has not been determined to date.

The objective: to evaluate the clinical efficacy and safety of standard PLND (sPLND) versus ePLND, in trimodal (combination with PCE and adjuvant chemotherapy – ACT) treatment of MIBC.

Materials and methods. A retrospective analysis of the results of treatment of 48 patients with MIBC after PCE in combination with sPLND or ePLND and ACT at the Kyiv City Clinical Oncology Center and the Oncourology Clinic of the Institute of Urology of the National Academy of Medical Sciences of Ukraine from 2012 to 2019 was conducted. During sPLND groups of external/internal iliac and obturator LN were dissected, at ePLND (in addition to these groups) – general iliac and presacral. The main indicators of effectiveness: general and cancer specific survival, life expectancy, recurrence-free survival. Safety indicators: frequency and nature of postoperative complications. Inclusion criteria: diagnosis of MIBC, stage of primary tumor from T2 to T4a, use in the program of examination of computed tomography/magnetic resonance imaging with contrast, removal of primary tumor by PCE (resection of the bladder with a bipolar electric knife, retreating from the tumor 0.8– cm to healthy tissues), sPLND/ePLND, ACT. Exclusion criteria – the presence of distant metastases. Statistical analysis: the significance of intergroup differences was determined by Pearson’s test (χ²). Significance level 0.05.

Results. The average age of patients (including 43 men and 5 women) in the general group was 62 years (mean age – 38-74 years). The distribution of patients by tumor location was as follows: lateral walls – 32 (66.7%), the bottom of the bladder – 16 (33.3%). According to the local spread of the tumor: T2a-T2b – 27 (56.25%), T3a-T3b – 17 (35.4%) T4a-T4b – 4 (8.3%). By histological type of tumor: transitional cell carcinoma – 39 (81.25%), adenocarcinoma – 5 (10.41%), squamous cell carcinoma – 4 (8.3%). By volume of PLND: standard – 29 (60.4%), extended – 19 (39.6%). The median follow-up was 29 months (12–42 months). By means of CT metastases in pelvic LN were detected in 8 (16.6%) patients. On average, 13 LN were removed. At sPLND the minimum volume of removal was 8 LN, at ePLND – 15 LN. In the group where PCE + sPLND + ACT was performed, metastatic LN lesions were present in 6 (20.7%) patients, in the group where PCE + ePLND + ACT – in 11 (57.9%). The number of affected LN was correspond to the depth of invasion of the primary tumor. In the group of PCE + sPLND + ACT, 80% of internal iliac LN were affected. In the group of PCE + ePLND + ACT in 63.6% of cases – general iliac LN and in 36.4% – general and obturator. ePLND on average prolonged the time of surgery by 40 minutes, but did not lead to an increase in the frequency of complications, and did not increase the duration of postoperative drainage. In the group, where ePLND was performed, the 5-year survival rate depended on the metastatic lesion of regional LN at the time of diagnosis: in the presence of metastases it was 30%, and in the absence – 62%. Patients with baseline metastatic LN lesion had a higher risk of tumor recurrence. Thus, in 7 (14.5%) of them there was a local recurrence (on average within 16 months after surgery), in 5 (10.4%) – distant metastases, in 2 (4.16%) – their combination. The most common postoperative complication in both groups was lymphorrhea, but more often after ePLND than after sPLND: 42.1% vs. 17.2%. The second most common complications were pyelonephritis (occurring in 10.5% and 6.9%, respectively) and hydronephrosis (occurring in 10.5% and 6.9%, respectively, between 30 and 90 days after ureteral reimplantation). Dynamic intestinal obstruction – 1 (5.2%) was registered least often (only in the ePLND group).

Conclusion. PCE in combination with PLND and ACT is a trimodal treatment of choice in MIBC patients, which allows to achieve fairly high 5-year survival (up to 60% in the absence of metastases) with better functional results (preservation of urinary function) and less trauma than with RC. The choice of PLND volume (standard or extended) should be determined by TNM stage, and the likelihood of developing lymphorrhea/lymphostasis. In the absence of a deep invasion of the bladder wall and metastases to common iliac and presacral LN, preference should be given to sPLND, as it is associated with a lower risk of lymphorrhea (twice lower than with ePLND). Further MIBC studies are needed to most effectively stratify patients for a particular treatment regimen.