World J Urol DOI 10.1007/s00345-014-1387-1
Original Article
Oncological outcomes of advanced muscle‑invasive bladder cancer with a micropapillary variant after radical cystectomy and adjuvant platinum‑based chemotherapy Alexandra Masson‑Lecomte · Evanguelos Xylinas · Morgane Bouquot · Mathilde Sibony · Yves Allory · Eva Comperat · Marc Zerbib · Alexandre de la Taille · Morgan Rouprêt
Received: 3 March 2014 / Accepted: 20 August 2014 © Springer-Verlag Berlin Heidelberg 2014
Abstract Objective To assess the oncological outcomes of radical cystectomy (RC) and adjuvant chemotherapy to treat muscle-invasive bladder cancer (MIBC) with a micropapillary component (MPC), and to compare outcomes with those from pure urothelial carcinoma (PUC). Materials and methods A retrospective review of clinicopathological and follow-up data was performed for all patients treated by RC and adjuvant platinum-based chemotherapy for advanced MIBC in three tertiary reference centers between 1999 and 2012. Uni- and multivariate Cox’s regression analyses evaluated the association of
A. Masson‑Lecomte (*) · A. de la Taille Department of Urology, Henri Mondor Academic Hospital, Paris Est Creteil University, Creteil, France e-mail: [email protected] E. Xylinas · M. Zerbib Department of Urology, Cochin Hospital, APHP, Paris Descartes University, Paris, France M. Bouquot · M. Rouprêt Academic Urology Unit, Pitié Salpêtriere Academic Hospital, Pierre et Marie Curie University, Paris, France e-mail: [email protected] M. Sibony Department of Pathology, Cochin Hospital, APHP, Paris Descartes University, Paris, France Y. Allory Department of Pathology, Henri Mondor Academic Hospital, Paris Est Creteil University, Creteil, France E. Comperat Department of Pathology, Pitié Salpêtriere Academic Hospital, Pierre et Marie Curie University, Paris, France
the presence of MPC with disease recurrence and cancerspecific mortality. Results Two hundred and thirty-five (88 %) PUC and 31 (12 %) MPC cases were included. Median age was 65 (39– 83) years in the PUC group and 62 (45–80) years in the MPC group. Median survival was 29 months in the MPC versus 31 months in the PUC group. No significant difference was observed between the groups regarding main clinical and pathological characteristics. The median number of treatment cycles administered was 6 (3–8) in the PUC versus 5 (3–8) in the MPC group (p = 0.45). Five-year disease-free recurrence and cancer-specific survival (CSS) rates were 15 and 24 %, respectively, in the MPC versus 42 and 47 %, respectively, in the PUC group (p = 0.007 and 0.058). In multivariate analyses, ASA score, soft tissue surgical margins, and MPC were associated with disease recurrence (p = 0.022, 0.001, and 0.015, respectively). We found no association between MPC and cancer-specific mortality (univariate, p = 0.06). Conclusion MPC was associated with higher recurrence rates after RC and platinum-based adjuvant chemotherapy than that with pure urothelial tumors. Keywords Urothelial carcinoma · Bladder neoplasm · Micropapillary variant · Radical cystectomy · Adjuvant chemotherapy · Survival
Introduction In the last 30 years, the mortality rate for bladder cancer has remained stable [1], whereas the mortality rates from other cancers, such as colon cancer, have halved [2]. Radical cystectomy (RC) remains the gold-standard treatment for non-metastatic muscle-invasive bladder cancer (MIBC)
13
[3]. Cisplatin-based adjuvant chemotherapy is proposed when the disease is found to be locally advanced [4]. In order to improve our selection of candidates suitable for adjuvant chemotherapy, four nomograms have been proposed in the postoperative setting. All of these predict the patient’s survival after RC, using standard clinicopathological features, such as age, gender, pT stage, the presence of carcinoma in situ, number of removed nodes, node positivity, lympho-vascular invasion, status of margins, and administration of adjuvant treatments [5–8]. Only one of these predictive tools has included a histological subtype in the list of requested items [5]. Moreover, in a large metaanalysis that evaluated adjuvant chemotherapy in bladder cancer patients, none of these criteria had an influence on survival outcomes [9]. Micropapillary carcinoma of the bladder (MPC) is a rare entity, representing less than 2 % of all urothelial tumors [10]. Since 2000, several clinicopathological studies have described it as a highly aggressive histological variant that is associated with high-stage and high-grade tumors [11–16]. However, studies have failed to demonstrate any independent impact of this variant on prognosis [17, 18]. It remains unclear whether this particular histological subtype benefits less from chemotherapy [19, 20]. The aim of our study was to assess whether MIBC patients with a MPC variant had worse survival outcomes after RC and adjuvant chemotherapy than patients with ‘pure’ urothelial carcinoma (PUC).
Materials and methods Study population A retrospective review was conducted of all patients with locally advanced MIBC. They were identified following pathology-specimen analysis [pT3–T4 N0 or any stage (pTa/T1/Tis/T2/T3/T4), and node positive] and had received platinum-based adjuvant chemotherapy at three institutions between 1999 and 2012. Data from 1175 consecutive executions of RC were available. RC was performed with extended pelvic lymph node dissection up to the aortic bifurcation. The following data were reviewed: age, gender, tumor and node stage (according to the AJCC TNM classification), grade (1973 WHO classification), number of removed and positives nodes, the presence of carcinoma in situ, status of surgical margins, lympho-vascular invasion, histological variations in RC specimens, adjuvant chemotherapy, and survival outcomes. Patients with metastatic disease or who had received neoadjuvant chemotherapy were excluded.
13
World J Urol
Chemotherapy regimen Cisplatin-based chemotherapy was the most common regimen, depending on the patient’s eligibility and renal function. Briefly, cisplatin was administered at a median dose of 70 mg/m2 of body-surface area (calculated using the appropriate formula from the height and weight of the patient). This was performed every 3 weeks if renal function and circulating blood elements were at acceptable levels (creatinine clearance ≥60 mL/min, platelets ≥100,000/mm2, and polymorphonuclear leukocytes ≥1,000/mm2). Patients who were unfit for cisplatin therapy, such as those with impaired renal function or a poor performance status, received a carboplatin-based regimen. Carboplatin was dosed to an AUC of 5 and administered every 3 weeks. Pathological analyses Surgical specimens were examined by genitourinary pathologists at each center. Only patients presenting with PUC or MPC were included in the analyses. MPC was defined as the presence of a micropapillary component on the RC specimen. Statistical analyses All patients were followed from diagnosis until death or until the data were censored (with the patient still alive). Recurrence was defined as disease occurring in the bladder bed, the regional lymph nodes, or the appearance of distant metastasis. Student’s t test was used to compare the means of continuous variables, and Pearson’s chi-squared test was used to compare the proportions of categorical variables. Kaplan–Meier analysis was used to estimate recurrence-free and CSS rates. These rates were compared using the logrank test. Uni- and multivariate Cox’s regression analyses were performed to assess the effect of clinical and pathological data on recurrence and cancer-specific mortality rates. All potential prognostic factors in the univariable analyses were included in multivariate analyses. A p value of
Original Article
Oncological outcomes of advanced muscle‑invasive bladder cancer with a micropapillary variant after radical cystectomy and adjuvant platinum‑based chemotherapy Alexandra Masson‑Lecomte · Evanguelos Xylinas · Morgane Bouquot · Mathilde Sibony · Yves Allory · Eva Comperat · Marc Zerbib · Alexandre de la Taille · Morgan Rouprêt
Received: 3 March 2014 / Accepted: 20 August 2014 © Springer-Verlag Berlin Heidelberg 2014
Abstract Objective To assess the oncological outcomes of radical cystectomy (RC) and adjuvant chemotherapy to treat muscle-invasive bladder cancer (MIBC) with a micropapillary component (MPC), and to compare outcomes with those from pure urothelial carcinoma (PUC). Materials and methods A retrospective review of clinicopathological and follow-up data was performed for all patients treated by RC and adjuvant platinum-based chemotherapy for advanced MIBC in three tertiary reference centers between 1999 and 2012. Uni- and multivariate Cox’s regression analyses evaluated the association of
A. Masson‑Lecomte (*) · A. de la Taille Department of Urology, Henri Mondor Academic Hospital, Paris Est Creteil University, Creteil, France e-mail: [email protected] E. Xylinas · M. Zerbib Department of Urology, Cochin Hospital, APHP, Paris Descartes University, Paris, France M. Bouquot · M. Rouprêt Academic Urology Unit, Pitié Salpêtriere Academic Hospital, Pierre et Marie Curie University, Paris, France e-mail: [email protected] M. Sibony Department of Pathology, Cochin Hospital, APHP, Paris Descartes University, Paris, France Y. Allory Department of Pathology, Henri Mondor Academic Hospital, Paris Est Creteil University, Creteil, France E. Comperat Department of Pathology, Pitié Salpêtriere Academic Hospital, Pierre et Marie Curie University, Paris, France
the presence of MPC with disease recurrence and cancerspecific mortality. Results Two hundred and thirty-five (88 %) PUC and 31 (12 %) MPC cases were included. Median age was 65 (39– 83) years in the PUC group and 62 (45–80) years in the MPC group. Median survival was 29 months in the MPC versus 31 months in the PUC group. No significant difference was observed between the groups regarding main clinical and pathological characteristics. The median number of treatment cycles administered was 6 (3–8) in the PUC versus 5 (3–8) in the MPC group (p = 0.45). Five-year disease-free recurrence and cancer-specific survival (CSS) rates were 15 and 24 %, respectively, in the MPC versus 42 and 47 %, respectively, in the PUC group (p = 0.007 and 0.058). In multivariate analyses, ASA score, soft tissue surgical margins, and MPC were associated with disease recurrence (p = 0.022, 0.001, and 0.015, respectively). We found no association between MPC and cancer-specific mortality (univariate, p = 0.06). Conclusion MPC was associated with higher recurrence rates after RC and platinum-based adjuvant chemotherapy than that with pure urothelial tumors. Keywords Urothelial carcinoma · Bladder neoplasm · Micropapillary variant · Radical cystectomy · Adjuvant chemotherapy · Survival
Introduction In the last 30 years, the mortality rate for bladder cancer has remained stable [1], whereas the mortality rates from other cancers, such as colon cancer, have halved [2]. Radical cystectomy (RC) remains the gold-standard treatment for non-metastatic muscle-invasive bladder cancer (MIBC)
13
[3]. Cisplatin-based adjuvant chemotherapy is proposed when the disease is found to be locally advanced [4]. In order to improve our selection of candidates suitable for adjuvant chemotherapy, four nomograms have been proposed in the postoperative setting. All of these predict the patient’s survival after RC, using standard clinicopathological features, such as age, gender, pT stage, the presence of carcinoma in situ, number of removed nodes, node positivity, lympho-vascular invasion, status of margins, and administration of adjuvant treatments [5–8]. Only one of these predictive tools has included a histological subtype in the list of requested items [5]. Moreover, in a large metaanalysis that evaluated adjuvant chemotherapy in bladder cancer patients, none of these criteria had an influence on survival outcomes [9]. Micropapillary carcinoma of the bladder (MPC) is a rare entity, representing less than 2 % of all urothelial tumors [10]. Since 2000, several clinicopathological studies have described it as a highly aggressive histological variant that is associated with high-stage and high-grade tumors [11–16]. However, studies have failed to demonstrate any independent impact of this variant on prognosis [17, 18]. It remains unclear whether this particular histological subtype benefits less from chemotherapy [19, 20]. The aim of our study was to assess whether MIBC patients with a MPC variant had worse survival outcomes after RC and adjuvant chemotherapy than patients with ‘pure’ urothelial carcinoma (PUC).
Materials and methods Study population A retrospective review was conducted of all patients with locally advanced MIBC. They were identified following pathology-specimen analysis [pT3–T4 N0 or any stage (pTa/T1/Tis/T2/T3/T4), and node positive] and had received platinum-based adjuvant chemotherapy at three institutions between 1999 and 2012. Data from 1175 consecutive executions of RC were available. RC was performed with extended pelvic lymph node dissection up to the aortic bifurcation. The following data were reviewed: age, gender, tumor and node stage (according to the AJCC TNM classification), grade (1973 WHO classification), number of removed and positives nodes, the presence of carcinoma in situ, status of surgical margins, lympho-vascular invasion, histological variations in RC specimens, adjuvant chemotherapy, and survival outcomes. Patients with metastatic disease or who had received neoadjuvant chemotherapy were excluded.
13
World J Urol
Chemotherapy regimen Cisplatin-based chemotherapy was the most common regimen, depending on the patient’s eligibility and renal function. Briefly, cisplatin was administered at a median dose of 70 mg/m2 of body-surface area (calculated using the appropriate formula from the height and weight of the patient). This was performed every 3 weeks if renal function and circulating blood elements were at acceptable levels (creatinine clearance ≥60 mL/min, platelets ≥100,000/mm2, and polymorphonuclear leukocytes ≥1,000/mm2). Patients who were unfit for cisplatin therapy, such as those with impaired renal function or a poor performance status, received a carboplatin-based regimen. Carboplatin was dosed to an AUC of 5 and administered every 3 weeks. Pathological analyses Surgical specimens were examined by genitourinary pathologists at each center. Only patients presenting with PUC or MPC were included in the analyses. MPC was defined as the presence of a micropapillary component on the RC specimen. Statistical analyses All patients were followed from diagnosis until death or until the data were censored (with the patient still alive). Recurrence was defined as disease occurring in the bladder bed, the regional lymph nodes, or the appearance of distant metastasis. Student’s t test was used to compare the means of continuous variables, and Pearson’s chi-squared test was used to compare the proportions of categorical variables. Kaplan–Meier analysis was used to estimate recurrence-free and CSS rates. These rates were compared using the logrank test. Uni- and multivariate Cox’s regression analyses were performed to assess the effect of clinical and pathological data on recurrence and cancer-specific mortality rates. All potential prognostic factors in the univariable analyses were included in multivariate analyses. A p value of
