Future directions in risk stratification and therapy for advanced pediatric genitourinary rhabdomyosarcoma

Miriam Harel, Fernando A. Ferrer, Linda H. Shapiro, John H. Makari

Research output: Contribution to journalReview article

19 Citations (Scopus)

Abstract

Rhabdomyosarcoma (RMS) represents the most common soft tissue sarcoma in infants and children and the third most common pediatric solid tumor, accounting for 5% to 15% of all childhood solid tumors. Of these, 15% to 20% arise from the genitourinary tract, with the most common sites originating from the prostate, bladder, and paratesticular regions, followed by the vagina and uterus. Although upfront radical surgery was used at the initiation of Intergroup RMS Study-I (1972–1978), the treatment paradigm has shifted to include initial biopsy with the goal of organ preservation, systemic chemotherapy for all patients, and local control involving surgical resection with or without radiation therapy for most patients. Collaborative group clinical trials have led to dramatic improvement in survival rates from 1960 to 1996 among patients with low- or intermediate-risk disease; however, outcomes appear to have plateaued in more recent years, and the prognosis for patients with metastatic or relapsed/refractory disease remains poor. Current management goals include minimizing toxicity while maintaining the excellent outcomes in low-risk disease, as well as improving outcomes in patients with intermediate- and high-risk disease. Advances in genetic analysis have allowed further refinement in risk stratification of patients. Perhaps the most significant recent development in RMS research was the discovery of an association of alveolar RMS (ARMS) with translocations t(2;13) and t(1;13). Translocation fusion-positive tumors comprise 80% of ARMS and are more aggressive. Fusion-negative ARMS may have a clinical course similar to embryonal RMS. Future Children׳s Oncology Group sarcoma studies will likely incorporate fusion status into risk stratification and treatment allocation. Newer radiotherapy modalities hold promise for providing local control of disease while minimizing morbidity. The addition of traditional cytotoxic chemotherapeutic agents does not seem to improve outcomes in high-risk patients. Ultimately, the most substantial progress may arise from further elucidation of genetic and molecular pathways involved in RMS tumor formation in an effort to identify novel, targeted therapeutic approaches.

Original languageEnglish (US)
Pages (from-to)103-115
Number of pages13
JournalUrologic Oncology: Seminars and Original Investigations
Volume34
Issue number2
DOIs
StatePublished - Feb 1 2016

Fingerprint

Rhabdomyosarcoma
Pediatrics
Sarcoma
Therapeutics
Neoplasms
Radiotherapy
Alveolar Rhabdomyosarcoma
Embryonal Rhabdomyosarcoma
Organ Preservation
Cytotoxins
Vagina
Direction compound
Uterus
Prostate
Molecular Biology
Urinary Bladder
Survival Rate
Clinical Trials
Morbidity
Biopsy

Keywords

  • Genitourinary
  • Multimodal therapy
  • Pediatric
  • Rhabdomyosarcoma
  • Risk stratification

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

Future directions in risk stratification and therapy for advanced pediatric genitourinary rhabdomyosarcoma. / Harel, Miriam; Ferrer, Fernando A.; Shapiro, Linda H.; Makari, John H.

In: Urologic Oncology: Seminars and Original Investigations, Vol. 34, No. 2, 01.02.2016, p. 103-115.

Research output: Contribution to journalReview article

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abstract = "Rhabdomyosarcoma (RMS) represents the most common soft tissue sarcoma in infants and children and the third most common pediatric solid tumor, accounting for 5{\%} to 15{\%} of all childhood solid tumors. Of these, 15{\%} to 20{\%} arise from the genitourinary tract, with the most common sites originating from the prostate, bladder, and paratesticular regions, followed by the vagina and uterus. Although upfront radical surgery was used at the initiation of Intergroup RMS Study-I (1972–1978), the treatment paradigm has shifted to include initial biopsy with the goal of organ preservation, systemic chemotherapy for all patients, and local control involving surgical resection with or without radiation therapy for most patients. Collaborative group clinical trials have led to dramatic improvement in survival rates from 1960 to 1996 among patients with low- or intermediate-risk disease; however, outcomes appear to have plateaued in more recent years, and the prognosis for patients with metastatic or relapsed/refractory disease remains poor. Current management goals include minimizing toxicity while maintaining the excellent outcomes in low-risk disease, as well as improving outcomes in patients with intermediate- and high-risk disease. Advances in genetic analysis have allowed further refinement in risk stratification of patients. Perhaps the most significant recent development in RMS research was the discovery of an association of alveolar RMS (ARMS) with translocations t(2;13) and t(1;13). Translocation fusion-positive tumors comprise 80{\%} of ARMS and are more aggressive. Fusion-negative ARMS may have a clinical course similar to embryonal RMS. Future Children׳s Oncology Group sarcoma studies will likely incorporate fusion status into risk stratification and treatment allocation. Newer radiotherapy modalities hold promise for providing local control of disease while minimizing morbidity. The addition of traditional cytotoxic chemotherapeutic agents does not seem to improve outcomes in high-risk patients. Ultimately, the most substantial progress may arise from further elucidation of genetic and molecular pathways involved in RMS tumor formation in an effort to identify novel, targeted therapeutic approaches.",
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