(UroToday.com) During the first testicular cancer session at the 2020 Annual Meeting of the Society of Urologic Oncology, Dr. Clint Cary tackled management of one of the rarest and difficult patient populations in urologic oncology: those with late recurrence or relapse of testicular cancer.
He began by clarifying the definitions of these patient categories and their treatments:
- Salvage surgery in this context refers to surgical treatment of growing disease or rising tumor markers following induction or salvage chemotherapy
- Late relapse refers to recurrence of disease at least 2 years after complete response to initial therapy of any kind (surgery or chemotherapy)
As there are no randomized trials available in this space, Dr. Cary’s talk focused on a review of the major case series.
Addressing salvage surgery first, Dr. Cary reviewed 3 series, one older series before the time of modern standard chemotherapy,1 and two more recent from his institution2,3. All patients had rising tumor markers after first- or second-line chemotherapy. In the earlier trial from Indiana (1977-2000), 114 patients underwent retroperitoneal lymph node dissection (RPLND) after first- or second-line chemotherapy. ~50% were found to have residual viable germ cell tumor. This histology in the retroperitoneum was, unsurprisingly, found to be the best predictor of 5-year overall survival (OS), with those with residual germ cell tumor having a 31% chance of survival vs ~75% for teratoma and ~85% for fibrosis alone. Though he did not present numbers for how many patients received further chemotherapy after RPLND, he did state that RPLND alone was curative for at least some of the 31% surviving with residual germ cell tumor.
In an updated series from Indiana being presented elsewhere at this year’s conference,3 representing 81 patients from 2005-2019, all patients undergoing RPLND for rising tumor markers after chemotherapy were found to have residual disease, which may reflect an improvement in diagnostic practices in the intervening years. 5-year OS for these patients was also improved (now 50%). 38.3% of patients had surgery after first-line chemotherapy and the remainder after salvage chemotherapy. 42% of patients normalized their serum tumor markers after RPLND. Patients with prior salvage chemotherapy faired significantly worse compared to those having received only first-line chemotherapy previously with overall survival of ~60% vs ~20%.
Trying to parse these numbers to make a statement about the utility of surgery in this setting is challenging, but as Dr. Cary summarized, it does seem that surgery has a role for select patients and can be curative.
Perhaps more compelling is the data he presented from two series of patients undergoing RPLND after high-dose chemotherapy.4,5 Despite heavy pretreatment with few remaining options for these patients, 5- year OS was still around 40-50% for patients who were found to have viable disease in the retroperitoneum, which gives some hope that RPLND is a worthwhile effort in these dire situations.
Dr. Cary then turned his attention to the treatment of late relapse of disease. An early study from Indiana published in 1995 established the primacy of surgical treatment for this disease after showing that chemotherapy alone was curative only in 3% of patients.6 This was reinforced by a more recent series showing far superior outcomes in patients who underwent complete resection vs those who underwent incomplete or no resection (5 year OS 79% vs 36%), though chemotherapy may play a role when added to surgery.7 Patients with late relapse after stage I disease may be especially good candidates for RPLND alone, as their outcomes are generally better than those with relapse after recurrent disease.8
Interestingly, 75% of late relapses were discovered >= 5 years after initial therapy, emphasizing a role for long-term post-treatment surveillance of these patients.
To summarize Dr. Cary emphasized two take-home points from his lecture:
- Salvage surgery can be curative for some well-selected patients whose disease can be completely resected, with good (30-50%) long-term survival.
- In late relapse, complete resection is the primary treatment and can be curative, especially for chemotherapy-naïve and asymptomatic patients.
Presented by: K. Clint Cary, MD, MPH, Associate Professor, Director, Center for Cancer and Health Equities, Indiana University Health Simon Cancer Center
Written by: Marshall Strother, MD, Society for Urologic Oncology Fellow, Division of Urologic Oncology, Fox Chase Cancer Center, Philadelphia PA @mcstroth during the 2020 Society of Urologic Oncology Annual Meeting – December 2-5, 2020 – Washington, DC
References:
1. Albers P, Ganz A, Hannig E, Miersch W-DE, Müller SC. Salvage surgery of chemorefractory germ cell tumors with elevated tumor markers. Journal of Urology. 2000;164(2):381-384.
2. Beck SD, Foster RS, Bihrle R, Einhorn LH, Donohue JP. Outcome analysis for patients with elevated serum tumor markers at postchemotherapy retroperitoneal lymph node dissection. J Clin Oncol. 2005 Sep 1;23(25):6149-56. doi: 10.1200/JCO.2005.11.684. PMID: 16135481.
3. Kern S, et al. Salvage Retroperitoneal Lymph Node Dissection in the Setting of Rising Tumor Markers in Relapsed Germ Cell Tumor, presented later at this meeting, Society of Urologic Oncology 21st Annual Meeting
4. Rick O, Bokemeyer C, Weinknecht S, Schirren J, Pottek T, Hartmann JT, Braun T, Rachud B, Weissbach L, Hartmann M, Siegert W, Beyer J. Residual tumor resection after high-dose chemotherapy in patients with relapsed or refractory germ cell cancer. J Clin Oncol. 2004 Sep 15;22(18):3713-9. doi: 10.1200/JCO.2004.07.124. PMID: 15365067.
5. Cary C, Pedrosa JA, Jacob J, Beck SD, Rice KR, Einhorn LH, Foster RS. Outcomes of postchemotherapy retroperitoneal lymph node dissection following high-dose chemotherapy with stem cell transplantation. Cancer. 2015 Dec 15;121(24):4369-75. doi: 10.1002/cncr.29678. Epub 2015 Sep 15. PMID: 26371446.
6. Baniel J, Foster RS, Gonin R, Messemer JE, Donohue JP, Einhorn LH. Late relapse of testicular cancer. J Clin Oncol. 1995 May;13(5):1170-6. doi: 10.1200/JCO.1995.13.5.1170. PMID: 7537800.
7. Sharp DS, Carver BS, Eggener SE, Kondagunta GV, Motzer RJ, Bosl GJ, Sheinfeld J. Clinical outcome and predictors of survival in late relapse of germ cell tumor. J Clin Oncol. 2008 Dec 1;26(34):5524-9. doi: 10.1200/JCO.2007.15.7453. Epub 2008 Oct 20. PMID: 18936477; PMCID: PMC2651099.
8. Rice KR, Beck SD, Pedrosa JA, Masterson TA, Einhorn LH, Foster RS. Surgical management of late relapse on surveillance in patients presenting with clinical stage I testicular cancer. Urology. 2014 Oct;84(4):886-90. doi: 10.1016/j.urology.2014.05.054. PMID: 25260450.