Combined Chemotherapy and Radiotherapy Improves Survival in 1897 Testicular Lymphoma Patients from a Contemporary Cohort - Beyond the Abstract

Primary testicular lymphoma (PTL) is a rare disease, found more frequently in older men. It is a unique extranodal presentation of non-Hodgkin lymphoma (NHL), with diffuse large B-cell lymphoma (DLBCL) the most frequent histology.1,2 Five-year overall survival (OS) rates have ranged from 68% to 86% according to recent reports.3-5 However, assessing outcomes among PTL patients can be challenging, due to the low prevalence of this disease.



Retrospective reports of PTL use small numbers of patients and/or include patients treated during preceding treatment eras. To understand the oncologic outcomes of PTL, it is important to assess the era during which patients received treatment, because of the evolution of therapies over time. The current standard of care for these patients is a combined treatment with orchiectomy, anthracycline-based chemotherapy (CHT) with rituximab, radiotherapy (RT) of the contralateral testis, and central nervous system (CNS) prophylaxis.2,3,5

For this study, we analyzed treatment patterns and survival of 1897 men with PTL to examine the impact of present-day treatments (including rituximab) on OS in PTL patients.

By querying the National Cancer Database (NCDB) NHL database from 2006 through 2016, we grouped patients based on receipt of treatment (1) standard of care (SOC) and (2) non-SOC groups. The SOC group included men who received a combination of orchiectomy, CHT, and RT. The non-SOC group included men who received (1) orchiectomy only, or (2) orchiectomy plus CHT, or (3) orchiectomy plus RT. A propensity score matching approach was used to account for differences in patient demographics to compare survival in the SOC and non-SOC groups.

Our results show a clear underutilization of SOC treatment, with only 47% of the entire cohort receiving CHT-RT after orchiectomy. Further data shows that the five-year OS is significantly worse across all disease stages for those that do not receive combined CHT + RT treatment after orchiectomy (Figure 1).
overall survival of standard of care

Figure 1. Kaplan-Meier estimates of overall survival of standard of care (SOC) and non-SOC groups by stage using propensity score-matched data. A log-rank test was used to compare curves.

Multivariable analyses on the unmatched dataset showed that receiving SOC treatment was a predictor of survival (hazard ratio 0.51, P <0.001) (Table 1). A Charlson Comorbidity Index score over 2, analytic stage over 2, and Medicaid or Medicare insurance were also predictors of mortality.

Table 1. Model associations with all-cause mortality for men with primary testicular lymphomas diagnosed from 2006 to 2013.

model associations with all cause mortality
One limitation of our study is its retrospective nature. Although clinical and demographic factors in our statistical models were adjusted, we are subject to unmeasured confounders related to the observational nature of our study. This study is also subject to selection biased since all patients underwent orchiectomy and were treated at Commission on Cancer (CoC) accredited hospitals.

Our study has several strengths: the NCDB includes about 70% of all U.S. patients diagnosed with cancer and is sourced from hospital registry data, which represents a broad array of facilities. This allowed us to analyze a more significant number of patients. This cohort, to our knowledge, represents one of the largest PTL cohorts ever reported. This study also used propensity matching to limit confounders associated with the database. Lastly, our analysis includes only patients treated after the regulatory approval of rituximab, reflecting a current treatment era.

These data highlight the need for improved management of PTL patients.

Written by: Fernando Caumont, Christopher Porter, Hannah DeBerg, John Burns, Jason Frankel, John Paul Flores

Virginia Mason Medical Center, Seattle, WA. Electronic address: ., Virginia Mason Medical Center, Seattle, WA., Benaroya Research Institute, Seattle, WA.

References:

  1. Zucca, E., A. Conconi, Tariq I. Mughal, A. H. Sarris, J. F. Seymour, U. Vitolo, R. Klasa et al. "Patterns of outcome and prognostic factors in primary large-cell lymphoma of the testis in a survey by the International Extranodal Lymphoma Study Group." Journal of Clinical Oncology 21, no. 1 (2003): 20-27.
  2. Surveillance E, and End Results Program. SEER Stat fact sheets: prostate cancer. 2018. https://seer.cancer.gov/statfacts/html/prost.html.
  3. Mazloom, Ali, Nathan Fowler, L. Jeffrey Medeiros, Puneeth Iyengar, Patrecia Horace, and Bouthaina S. Dabaja. "Outcome of patients with diffuse large B-cell lymphoma of the testis by era of treatment: the MD Anderson Cancer Center experience." Leukemia & lymphoma 51, no. 7 (2010): 1217-1224.
  4. Vitolo, Umberto, Annalisa Chiappella, A. J. Ferreri, Maurizio Martelli, Ileana Baldi, Monica Balzarotti, Chiara Bottelli et al. "First-line treatment for primary testicular diffuse large B-cell lymphoma with rituximab-CHOP, CNS prophylaxis, and contralateral testis irradiation: final results of an international phase II trial." (2011): 2766-2772.
  5. Deng, L., Z. Y. Xu-Monette, Sanam Loghavi, G. C. Manyam, Y. Xia, C. Visco, J. Huh et al. "Primary testicular diffuse large B-cell lymphoma displays distinct clinical and biological features for treatment failure in rituximab era: a report from the International PTL Consortium." Leukemia 30, no. 2 (2016): 361-372.
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