Superior efficacy of neoadjuvant chemotherapy and radical cystectomy in cT3‐4aN0M0 compared to cT2N0M0 bladder cancer

Hermans, Tom J.N.; Voskuilen, Charlotte S.; Deelen, Marc; Mertens, Laura S.; Horenblas, Simon; Meijer, Richard P.; Boormans, Joost L.; Aben, Katja K.H.; Heijden, Michiel S. van der; Pos, Floris J.; Wit, Rianne de; Beerepoot, Laurens V.; Verhoeven, Rob H.A.

doi:10.1002/ijc.31833

“…Nitta et al analyzed the pathological outcomes of < pT2 stage, with the result that NAC group had a significantly higher rate of < pT2 stage with T2 stage than the non-NAC group [ 23 ]. Hermans et al, Martinez-Pineiro et al, and Ploussard et al stated that proportion of complete pathological downstaging was higher in NAC group compared to upfront RC for both T2 stage and T3-4 [ 18 , 24 , 27 ]. This was associated with better survival rate ( p = 0.0142) compared to patients without similar pathological downstage results [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Meta-analysis of neoadjuvant chemotherapy compared to radical cystectomy alone in improving overall survival of muscle-invasive bladder cancer patients

Hamid

¹

,

Ridwan

²

,

Parikesit

³

et al. 2020

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Background Most patients with muscle-invasive bladder cancer (MIBC) developed metastasis within 2 years, even after radical cystectomy (RC). The recurrence rate of MIBC was more than 50% of the cases. A meta-analysis conducted by Yin et al. showed that neoadjuvant chemotherapy (NAC) + RC improves overall survival in MIBC compared with RC only. However, a new meta-analysis by Li et al. concluded that NAC + RC was not superior to RC only in improving overall survival. The inconsistencies of these studies required further comprehensive analysis to recommend NAC use in bladder cancer treatment. Therefore, this meta-analysis aims to analyze previous studies that compare the efficacy of NAC + RC versus RC only to improve overall survival of MIBC. Methods The articles were searched using Pubmed with keywords “muscle-invasive bladder cancer”, “neoadjuvant chemotherapy”, “cystectomy”, and “overall survival”. The articles that were published until June 2020 were screened. The overall survival outcome was analyzed as hazard ratio (HR) and presented in a forest plot. Result Seventeen studies were included in meta-analysis with a total sample of 13,391 patients, consist of 2890 received NAC followed by RC and 10,418 underwent RC only. Two studies used methotrexate/vinblastine/doxorubicin/cisplatin (MVAC), two studies used gemcitabine/cisplatin (GC), one study used Cisplatin-based regimen, one study used MVAC or GC, one study used gemcitabine/carboplatin (GCarbo) or GC or MVAC, one study used Cisplatin/Gemcitabine or MVAC, one study used Cisplatin only, one study used Cisplatin-based (GC, MVAC) or non-Cisplatin-based (combined paclitaxel/gemcitabine/carboplatin), one study used GC, MVAC, Carboplatin, or Gemcitabine/Nedaplatin (GN), and five studies did not mention the regimen The overall survival in the NAC + RC only group was significantly better than the RC only group (HR 0.82 [0.71–0.95], p = 0.009). Conclusion NAC + RC is recommended to improve overall survival in MIBC patients. A further study assessing side effects and quality of life regarding NAC + RC is needed to establish a strong recommendation regarding this therapy.

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“…One study included a variety of regimens, such as carboplatin regimen and cisplatin regimen [ 23 ]. NAC regimen was not mentioned in 4 studies [ 19 , 21 , 22 , 24 ]. Cisplatin doses were 70 mg/m 2 every cycle for 2 cycles (two trials) or for 3 cycles (four trials).…”

Section: Resultsmentioning

confidence: 99%

Neoadjuvant Chemotherapy for Different Stages of Muscle-Invasive Bladder Cancer: A Systematic Review and Meta-analysis

Liu

¹

,

Yao

²

,

Guan

³

et al. 2022

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The purpose of this meta-analysis is to determine the survival benefits and pathological outcomes of neoadjuvant chemotherapy (NAC) combined with radical cystectomy (RC) administered to patients with cT2 or cT3-4N0M0 muscle-invasive bladder cancer (MIBC). PubMed, Embase, and the Cochrane Library were searched for comparing the use of NAC in combination with RC and RC alone in patients with different MIBC stages. A fixed effects model was used to calculate hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CIs), and the I 2 statistic was used to assess heterogeneity. Moreover, we determined possible sources of heterogeneity by subgroup and sensitivity analyses. Fifteen studies were finally selected. For cT2 bladder cancer, NAC combined with RC significantly increased the rates of pathological complete response (pCR) ( OR = 4.84 , 95% CI: 1.18–19.92, p = 0.029 ) but did not improve overall survival (OS) ( HR = 0.86 , 95% CI: 0.72–1.02, p = 0.078 ) across six studies. Regarding cT3-4 bladder cancer, NAC has a significantly improved effect on OS ( HR = 0.69 ; 95% CI: 0.59–0.81, p < 0.001 , across seven studies and 5726 patients) and pCR (pooled OR = 4.80 ; 95% CI: 2.06–11.23, p < 0.001 , across two studies) than RC alone. Most studies were randomized prospective trials (level 1 evidence), and all the effects were irrespective of the type of study design and did not vary between subgroups of patients. In conclusion, NAC combined with RC is recommended for patients with T3-4aN0M0 but not for patients with T2N0M0.

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“…Patients diagnosed with cT2-4aN0M0 urothelial bladder carcinoma (BC) who underwent RC plus PLND with or without NAC or neoadjuvant radiotherapy (NAR), between January 1st 1995 and December 31st 2013 (retrospective NCR cohort, data already available from Hermans et al [ 8 ]) and between November 1st 2017 and October 31st 2019 (prospective NCR-BlaZIB cohort) were selected from the Netherlands Cancer Registry (NCR). The NCR-BlaZIB cohort consisted of patients included in the ongoing Dutch nationwide population-based prospective BlaZIB study (BlaaskankerZorg In Beeld, translation: Insight into Bladder Cancer Care) [ 12 ], which is embedded in the NCR.…”

Section: Methodsmentioning

confidence: 99%

“…In a previous study, all pathology reports of patients from the NCR cohort 1995–2013 were reviewed (TH, MD, CV, LM) after linkage with PALGA since pathological downstaging at RC to non-MIBC was not registered in the NCR as a standard item before 2017 [ 8 ]. For the NCR-BlaZIB cohort, information on pathological downstaging was prospectively collected.…”

Section: Methodsmentioning

confidence: 99%

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Occult lymph node metastases in patients without residual muscle-invasive bladder cancer at radical cystectomy with or without neoadjuvant chemotherapy: a nationwide study of 5417 patients

Hoogstraten¹,

Gennep

²

,

Kiemeney³

et al. 2021

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Purpose Little is known about the prevalence of occult lymph node metastases (LNM) in muscle-invasive bladder cancer (MIBC) patients with pathological downstaging of the primary tumor. We aimed to estimate the prevalence of occult LNM in patients without residual MIBC at radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC) or neoadjuvant radiotherapy (NAR), and to assess overall survival (OS). Methods Patients with cT2-T4aN0M0 urothelial MIBC who underwent RC plus pelvic lymph node dissection (PLND) with curative intent between January 1995–December 2013 (retrospective Netherlands Cancer Registry (NCR) cohort) and November 2017–October 2019 (prospective NCR-BlaZIB cohort (acronym in Dutch: BlaaskankerZorg In Beeld; in English: Insight into bladder cancer care)) were identified from the nationwide NCR. The prevalence of occult LNM was calculated and OS of patients with <(y)pT2N0 vs. <(y)pT2N+ disease was estimated by the Kaplan–Meier method. Results In total, 4657 patients from the NCR cohort and 760 patients from the NCR-BlaZIB cohort were included. Of 1374 patients downstaged to <(y)pT2, 4.3% (N = 59) had occult LNM 4.1% (N = 49) of patients with cT2-disease and 5.6% (N = 10) with cT3-4a-disease. This was 4.0% (N = 44) in patients without NAC or NAR, 4.5% (N = 10) in patients with NAC, and 13.5% (N = 5) in patients with NAR but number of patients treated with NAR and downstaged disease was small. The prevalence of <(y)pT2N+ disease was 4.2% (N = 48) in the NCR cohort and 4.6% (N = 11) in the NCR-BlaZIB cohort. For patients with <(y)pT2N+ and <(y)pT2N0, median OS was 3.5 years (95% CI 2.5–8.9) versus 12.9 years (95% CI 11.7–14.0), respectively. Conclusion Occult LNM were found in 4.3% of patients with cT2-4aN0M0 MIBC with (near-) complete downstaging of the primary tumor following RC plus PLND. This was regardless of NAC or clinical T-stage. Patients with occult LNM showed considerable worse survival. These results can help in counseling patients for bladder-sparing treatments.

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Superior efficacy of neoadjuvant chemotherapy and radical cystectomy in cT3‐4aN0M0 compared to cT2N0M0 bladder cancer

Cited by 28 publications

References 22 publications

Meta-analysis of neoadjuvant chemotherapy compared to radical cystectomy alone in improving overall survival of muscle-invasive bladder cancer patients

Meta-analysis of neoadjuvant chemotherapy compared to radical cystectomy alone in improving overall survival of muscle-invasive bladder cancer patients

Neoadjuvant Chemotherapy for Different Stages of Muscle-Invasive Bladder Cancer: A Systematic Review and Meta-analysis

Occult lymph node metastases in patients without residual muscle-invasive bladder cancer at radical cystectomy with or without neoadjuvant chemotherapy: a nationwide study of 5417 patients

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