This article will explain the medical treatment section of the guidelines to facilitate better understanding and compliance by medical oncologists and urologic oncologists in China, so that patients can benefit more from more standardized clinical treatment.
Adjuvant and Neoadjuvant Chemotherapy for Bladder Cancer For patients with muscle-invasive bladder cancer, chemotherapy is an important component of treatment. A growing body of evidence supports neoadjuvant chemotherapy for bladder cancer staged T2 or T3 prior to total bladder resection. Two randomized clinical studies have shown a survival benefit of neoadjuvant chemotherapy, particularly for lesions with clinical stage T3. One included 307 bladder cancers with muscle invasion randomized to radical bladder resection alone or surgery after 3 cycles of preoperative MVAC regimen neoadjuvant chemotherapy and showed that neoadjuvant chemotherapy improved median survival (77 vs 46 months) and significantly reduced lesion residual rates, while neoadjuvant chemotherapy did not increase treatment-related mortality. An additional meta-analysis involving 11 clinical studies of 3005 patients with bladder cancer showed that cisplatin-based neoadjuvant chemotherapy improved five-year survival as well as disease-free survival. Therefore, the 2015 edition of the NCCN guidelines recommends cisplatin-based neoadjuvant chemotherapy for bladder cancer patients with T2 stage or higher as level 1 evidence. Based on the better tolerability and efficacy of dose dense MVAC regimens compared to conventional MVAC regimens and the equivalence of GC regimens to conventional MVAC regimens, neoadjuvant chemotherapy regimens are recommended for 3-4 cycles of dose dense MVAC (DDMVAC) regimens, GC regimens or CMV regimens. In contrast, for patients with renal insufficiency, the NCCN guidelines do not recommend carboplatin as an alternative to cisplatin in neoadjuvant chemotherapy, and such patients are not recommended for neoadjuvant chemotherapy.
For patients with preserved bladder, local radiotherapy after electrodesiccation should be accompanied by simultaneous chemotherapy for sensitization, and specific drugs can be used in the regimen of single-agent cisplatin, cisplatin combined with fluorouracil, fluorouracil combined with mitomycin, and cisplatin combined with paclitaxel, with recommended evidence of level 2B.
As for postoperative adjuvant chemotherapy for bladder cancer, due to the lack of large-scale randomized prospective controlled clinical studies and the conflicting conclusions of some corresponding clinical studies, adjuvant chemotherapy cannot be confirmed at this stage to delay recurrence or prolong survival. It is generally believed that for patients with bladder cancer with pathological stage T2 and below, and without lymph node metastasis, the risk of recurrence is low and postoperative adjuvant chemotherapy is not recommended. In contrast, for patients with pathologic stage T3 and above, or lymph node metastasis, because of their high risk of recurrence, postoperative adjuvant chemotherapy has been shown to reduce mortality by 30% in this group of high-risk patients; therefore, if such patients do not receive neoadjuvant chemotherapy preoperatively, postoperative adjuvant chemotherapy is usually recommended with a level 2B recommendation evidence.
Treatment of metastatic bladder cancer For inoperable and metastatic bladder cancer, a combination of chemotherapy-based treatment should be used. A randomized controlled phase III clinical study comparing GC regimen with standard MVAC regimen for advanced bladder cancer showed that the objective effective rate was 49% versus 46%, and the median survival time was 14.0 months versus 15.2 months, and the median PFS time was 7.7 months versus 8.3 months, respectively, with no significant difference between the two groups. The GC regimen was confirmed to be equivalent to the standard MVAC regimen, while the GC regimen was significantly better than the MVAC regimen in terms of tolerability. In another phase III clinical study comparing the dose-dense MVAC regimen with the standard MVAC regimen, the median follow-up was 7.3 years, with survival rates of 24.6% versus 13.2%, and the dose-dense MVAC regimen was better tolerated. Based on the two randomized controlled clinical studies, the NCCN guidelines recommend the dose-dense MVAC regimen versus the GC regimen as Class 1 evidence for first-line chemotherapy in inoperable or metastatic bladder cancer. For patients with renal insufficiency, gemcitabine in combination with carboplatin and methotrexate in combination with carboplatin and vincristine have objective efficacy rates of 42% and 30%, so the NCCN guidelines consider carboplatin as an alternative to cisplatin for patients with renal insufficiency.
Paclitaxel is also an effective chemotherapeutic agent for bladder cancer, and the efficacy of paclitaxel combined with cisplatin and paclitaxel combined with gemcitabine has been verified in phase I/II clinical studies. As for the three-drug combination regimen (PCG) of paclitaxel combined with cisplatin and gemcitabine, a phase III randomized controlled clinical study (ECORT30987) compared whether it was superior to the GC regimen for metastatic uroepithelial carcinoma and showed that the objective efficiency was 55.5% versus 43.6%, the median overall survival time was 15.8 versus 12.7 months, and the median PFS time was 8.3 versus The incidence of neutropenia was significantly higher in the three-drug treatment group than in the GC regimen, so the NCCN guideline expert committee concluded that patients had limited benefit from PCG regimen treatment and did not recommend it. However, subgroup analysis of patients with metastatic uroepithelium with primary lesions originating from the bladder showed a significantly better median OS in the PCG treatment group than in the GC treatment group (15.9 vs. 11.9 months), so the PCG regimen may still be beneficial for some patients. Although not recommended by NCCN guidelines, based on this trial, the above regimen without cisplatin, i.e. paclitaxel combined with gemcitabine, could be recommended as first-line treatment for patients with renal insufficiency or other comorbidities in combination, with a recommendation level of 2B.
For second-line treatment of metastatic bladder cancer, no standard treatment recommendation has been made, and NCCN guidelines strongly recommend that patients participate in the appropriate clinical studies. In actual clinical practice, if there are no corresponding clinical studies, single-agent regimens such as single-agent docetaxel, paclitaxel or gemcitabine can be selected as second-line agents based on the first-line regimen use, but the efficacy of second-line chemotherapy is limited and more effective treatment options still need to be explored.
Treatment of bladder cancer of non-uroepithelial origin The main pathological type of bladder cancer is uroepithelial cancer, but there are still a small number of non-uroepithelial pathological types, including adenocarcinoma as well as squamous cancer. The treatment of these patients should be pathologically based, multidisciplinary and comprehensive, with surgery still being the mainstay, radiotherapy being an important therapeutic component, and chemotherapy being under-practiced and not yet standardly recommended.
In conclusion Based on the current status of the urologic oncology specialty in China, the medical treatment of bladder cancer still needs to be further standardized in China by studying the guidelines and applying them in clinical practice so that patients with bladder cancer can receive standardized treatment and thus benefit overall.