Dr. Brant Inman took the position of metastasectomy for M+ patients. He started by noting that what the patient wants is a cure. What drugs usually give is some tumor shrinkage, toxicity, and cost, and what drugs rarely give is complete shrinkage (and for how long?). Key considerations for metastasectomy according to Dr. Inman include (i) patient comorbidity, (ii) disease burden, (iii) tumor location, and (iv) timing.
The principle for patient comorbidity is to not kill the patient, which includes assessing age, the severity of disease, and the patient’s life-expectancy without cancer. A recent study from SEER-Medicare examined the use and outcomes of metastasectomy in 70,648 patients ≥65 years of age with urothelial carcinoma; among these 497 patients had at least one metastasectomy1. The median overall survival (OS) after the first metastasectomy was 19 months (95%CI 15-23), and over a third of patients were alive at 3 years. The median length of stay after metastasectomy was 7 days (IQR: 4-12), and 10% of patients had at least 1 complication within 30 days of discharge; 30-day mortality after metastasectomy was 10%. Dr. Inman notes that in well-selected patients, appropriate outcomes are achievable.
The principle of disease burden is that surgery is unlikely to cure widespread disease. In Dr. Inman’s opinion, single disease site is better than multiple, one organ is better than two and one compartments is better than more. There is precedence for this in bladder cancer with extended pelvic lymphadenectomy. In a Danish study, 336 consecutive patients underwent radical cystectomy and extended pelvic lymphadenectomy without preoperative or postoperative chemotherapy2. The 5-year overall and recurrence-free survival rates in the entire study population were 68% and 69%, respectively. Overall, 64 patients (19%) had lymph node metastases of whom 22 (34.4%) had lymph node involvement above the bifurcation of the common iliac vessels outside the template of the standard lymph node dissection. Of note, the overall 5-year survival rates were similar in patients with lymph node involvement above the bifurcation of the common iliac vessels (37%) compared to the entire population with lymph node metastasis (41%) and to those with lymphatic metastases in the true pelvis below the bifurcation of the common iliac vessels (42%).
The principle of tumor location is that some sites are worse than others. According to Dr. Inman, nodal metastasectomy is better than lung, which is better than the brain, which is better than liver and bone. Work on predictive modeling of OS from the RISC group among patients with metastatic urothelial carcinoma found that several factors predict OS in patients receiving first-line combination based chemotherapy: performance status, white blood cell count, body mass index, ethnicity, lung, liver, or bone metastases, and prior perioperative chemotherapy3.
The principle of timing is that when the metastasis occurs matters. Dr. Inman notes that whether the metastases are synchronous or metachronous and whether the event occurred before or after chemotherapy are important considerations. In his opinion, chemotherapy response is a good selection tool for who may be a candidate for metastasectomy. In an Italian study, Necchi et al4 assessed 157 patients with locally advanced or metastatic urothelial carcinoma received first-line chemotherapy consisting of mMVAC; patients with subdiaphragmatic nodal disease and/or local recurrence only and who experienced at least stable disease were selected (n=59). Of these, 28 underwent surgery and 31 started consolidation chemotherapy with or without radiotherapy or observation. Among the 28 patients undergoing surgery, there were 14 PLND and 14 RPLND. Seven patients had achieved a complete response or partial response and stable disease (n = 21). Over a median follow-up of 88 months, the median PFS was 18 and 11 months, respectively, in favor of the surgical cohort vs consolidative chemotherapy (p = 0.009).
Dr. Inman concluded with several take-home messages supporting his stance regarding metastasectomy for bladder urothelial carcinoma patients:
- Metastatic bladder cancer is not always a death sentence
- Not all patients are good candidates for metastasectomy
- The best outcomes are achieved with multi-modal treatment: chemotherapy à surgery
Presented by: Professor James Catto MB ChB Ph.D. FRCS (Urol), Department of Oncology & Metabolism, The Medical School, Sheffield, United Kingdom and Brant A. Inman, MD, MS, Surgical Oncologist, Urologic Oncologist, Urologist, Duke University, Durham, North Carolina
Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University - Medical College of Georgia Twitter: @zklaassen_md at the 34th European Association of Urology (EAU 2019) #EAU19 conference in Barcelona Spain, March 15-19, 2019.
- Faltas BM, Gennarelli RL, Elkin E, et al. Metastasectomy in older adults with urothelial carcinoma: Population-based analysis of use and outcomes. Urol Oncol 2018 Jan;36(1):9.e11-9.e17
- Steven K, Poulsen AL. Radical cystectomy and extended pelvic lymphadenectomy: survival of patients with lymph node metastasis above the bifurcation of the common iliac vessels treated with surgery only. J Urol 2007 Oct;178(4 Pt 1):1218-1213.
- Necchi A, Sonpavde G, Lo Vullo S, et al. Nomogram-based prediction of overall survival in patients with metastatic urothelial carcinoma receiving first-line platinum-based chemotherapy: Retrospective Internation Study of Invasive/Advanced Cancer of the Urothelium (RISC).
- Necchi A, Giannatempo P, Lo Vullo S, et al. Postchemotherapy lymphadenectomy in patients with metastatic urothelial carcinoma: long-term efficacy and implications for trial design. Clin Genitourin Cancer 2015 Feb;13(1):80-86.
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