Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3–pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994): an intergroup, open-label, randomised phase 3 trial

Sternberg, Cora N.; Skoneczna, Iwona; Kerst, J. Martijn; Albers, Peter; Fosså, Sophie D.; Agerbæk, Mads; Dumez, Herlinde; Santis, Maria De; Théodore, Christine; Leahy, Michael; Chester, John D.; Verbaeys, Antony; Daugaard, Gedske; Wood, Lori; Witjes, J. Alfred; Wit, Ronald de; Geoffrois, L.; Sengeløv, Lisa; Thalmann, George N.; Charpentier, Danielle; Rolland, Frédéric; Mignot, L.; Sundar, Santhanam; Symonds, Paul; Graham, John D.; Joly, Florence; Marréaud, Sandrine; Collette, Laurence; Sylvester, Richard

doi:10.1016/s1470-2045(14)71160-x

Cited by 323 publications

(177 citation statements)

References 28 publications

Supporting

Mentioning

153

Contrasting

Unclassified

Order By: Relevance

“…184 After a median followup of seven years, the absolute mortality rates were 47% for the adjuvant treatment group and 57% for the delayed treatment group. However, the difference was not statistically significant (adjusted HR 0.78, 95% CI 0.56-1.08; p=0.13).…”

mentioning

confidence: 94%

Recommendations for the improvement of bladder cancer quality of care in Canada: A consensus document reviewed and endorsed by Bladder Cancer Canada (BCC), Canadian Urologic Oncology Group (CUOG), and Canadian Urological Association (CUA), December 2015

Kassouf

Aprikian

Black

et al. 2016

CUAJ

View full text Add to dashboard Cite

This initiative was undertaken in response to concerns regarding the variation in management and in outcomes of patients with bladder cancer throughout centres and geographical areas in Canada. Population-based data have also revealed that real-life survival is lower than expected based on data from clinical trials and/or academic centres. To address these perceived shortcomings and attempt to streamline and unify treatment approaches to bladder cancer in Canada, a multidisciplinary panel of expert clinicians was convened last fall for a two-day working group consensus meeting. The panelists included urologic oncologists, medical oncologists, radiation oncologists, patient representatives, a genitourinary pathologist, and an enterostomal therapy nurse. The following recommendations and summaries of supporting evidence represent the results of the presentations, debates, and discussions. Methodology

show abstract

mentioning

confidence: 94%

Recommendations for the improvement of bladder cancer quality of care in Canada: A consensus document reviewed and endorsed by Bladder Cancer Canada (BCC), Canadian Urologic Oncology Group (CUOG), and Canadian Urological Association (CUA), December 2015

Kassouf

Aprikian

Black

et al. 2016

CUAJ

View full text Add to dashboard Cite

show abstract

“…Patients were randomized to immediate treatment and deferred treatment groups. The study found no significant improvement in overall survival in the immediate treatment group compared to the treatment-deferred group [61]. This suggests that the timing of adjuvant or early salvage chemotherapy following cystectomy does not impact survival.…”

Section: Adjuvant Chemotherapymentioning

confidence: 80%

Current Concepts in the Management of Muscle Invasive Bladder Cancer

Krishna

Konety

2016

Indian J Surg Oncol

View full text Add to dashboard Cite

Bladder cancer is the ninth most common cancer in the world. Twenty to twenty-five percent of all newly diagnosed bladder cancers are muscle invasive in nature, and further, 20-25% of patients who are diagnosed with high-risk nonmuscle invasive disease will eventually progress to muscle invasive disease in due course of time irrespective of adjuvant intravesical therapies. Availability of newer imaging modalities improves appropriate identification of patients with muscle invasive disease. Radical cystectomy remains the mainstay of treatment for management of muscle invasive disease. Availability of neoadjuvant chemotherapy has improved overall survival. Risk stratification systems are now in consideration to identify patients who benefit maximally from neoadjuvant chemotherapy. Urinary diversion is a major cause of morbidity in these patients, and several strategies are being employed to reduce morbidity. In this article, we review available literature on various aspects of management of muscle invasive disease. Histologically, over 90% of bladder tumors are transitional cell carcinomas. The other subtypes, such as squamous cell and adenocarcinoma, are uncommon and account for 5 and <2%, respectively. Bladder cancer is a heterogeneous disease with a variable natural progression. Urothelial carcinomas can have a component of Bvariant histology^such as squamous differentiation, micropapillary, or adenocarcinoma. Micropapillary variant of urothelial carcinoma is associated with worse prognosis than pure urothelial carcinoma. Around 70% of the patients present with tumors that are superficial and have a tendency to recur. The remaining 30% present with muscle invasive tumors [4]. PathologyLow-grade tumors represent 50-60% of the cases. Majority of the tumors are stage Ta, i.e., confined to the urothelium. These tumors tend to recur and generally require repeated transurethral resection (TURBT) and surveillance cystoscopies [5].High-grade (HG) lesions account for 20-25% of all new cases. These lesions can either be sessile or papillary lesions. These tumors have a tendency to invade into the bladder wall if left untreated, especially in the presence of carcinoma in situ (CIS). Despite treatment in the form TURBT and chemotherapy, more than 20% of the patients with high-grade lesions progress to muscle invasive bladder cancer (MIBC) [6,7]. This has led to a lot of controversy regarding aggressive treatment in the form of early radical cystectomy vs. TURBT along with intravesical therapy, particularly in patients with HG

show abstract

“…Accordingly, several large trials were planned to compare immediate adjuvant chemotherapy versus the same treatment administered at recurrence, or comparing adjuvant therapy versus sequential therapy. Like the preceding trials, all of these closed prematurely due to poor accrual, and thus they were unable to demonstrate a clear benefit of adjuvant chemotherapy [31,32].…”

Section: • Adjuvant Chemotherapymentioning

confidence: 99%

Systemic Therapy for Bladder Cancer Finally Comes into a New Age

Zibelman

Plimack

2016

Future Oncol.

View full text Add to dashboard Cite

Systemic therapy for bladder cancer, both localized muscle-invasive disease and metastatic disease, has seen minimal progress over the past two decades. Current approaches rely upon cytotoxic chemotherapy combinations aimed at increasing cure rates or achieving palliation and disease control, but these regimens are fraught with short-and long-term toxicities and outcomes remain suboptimal. The emergence of systemic immunotherapies that can provide durable remissions in subsets of patients with other malignancies has the potential to transform the field, and early phase trials have begun to demonstrate activity in some patients with metastatic bladder cancer. In this article, we review the current state of systemic therapy for bladder cancer and discuss the current literature and ongoing trials utilizing various immunotherapies. KEYWORDS• bladder cancerCancers of the urinary bladder are the sixth most commonly diagnosed malignancy in the USA and the most prevalent malignancy of the GI tract, with 74,000 new cases estimated from 2015 [1]. The predominant histologic subtype is urothelial carcinoma (UC), which accounts for more than 90% of diagnoses in the western world. For patients with muscle-invasive bladder cancer (MIBC) confined to the bladder and deemed surgical candidates, radical cystectomy (RC) with pelvic lymphadenectomy remains the gold standard, with bladder preservation techniques using combinations of radiation therapy (RT) and systemic therapy receiving increased attention [2][3][4][5]. Local therapy with surgery or radiation alone is suboptimal, with median overall survival (OS) ranging from 1.8 to 3.8 years and 5-year survival of only 43% after RC and less than 40% with RT, with the majority of deaths related to distant disease [6,7]. The addition of neoadjuvant chemotherapy (NAC) has significantly improved outcomes. For patients who present with metastatic disease, systemic chemotherapy with cisplatin-based regimens, long recognized as an active drug in this disease, is accepted as the standard of care. Thus, systemic therapy is an integral component of treatment for patients with UC, yet despite tremendous advances across a multitude of malignant conditions, no new therapies have entered the armamentarium in over decade. Fortunately, recent and ongoing research in the burgeoning field of cancer immunotherapy (IT) offers hope that new agents will finally demonstrate survival benefits in clinical trials. In this article, we review the definitive studies that have established the current standards of care for systemic treatment in UC, then focus on new and future trials aiming to bring the systemic treatment of UC into the IT age.For reprint orders, please contact: reprints@futuremedicine.com

show abstract

Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3–pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994): an intergroup, open-label, randomised phase 3 trial

Abstract: Lilly, Canadian Cancer Society Research.

Cited by 323 publications

References 28 publications

Recommendations for the improvement of bladder cancer quality of care in Canada: A consensus document reviewed and endorsed by Bladder Cancer Canada (BCC), Canadian Urologic Oncology Group (CUOG), and Canadian Urological Association (CUA), December 2015

Recommendations for the improvement of bladder cancer quality of care in Canada: A consensus document reviewed and endorsed by Bladder Cancer Canada (BCC), Canadian Urologic Oncology Group (CUOG), and Canadian Urological Association (CUA), December 2015

Current Concepts in the Management of Muscle Invasive Bladder Cancer

Systemic Therapy for Bladder Cancer Finally Comes into a New Age

Contact Info

Product

Resources

About