Cancer Screening in the Pediatric Cancer Patient: A Focus on Genitourinary Malignancies and Why a Urologist Needs to Know About This? – Beyond the Abstract

In the United States, approximately 11,000 children are diagnosed with cancer every year.   Multiple advances in our diagnostic acumen and treatment strategies have resulted in an overall five-year cancer-free survival rate of 80%.1-3  Although the primary goal of treatment is to have the child survive the malignancy, the long-term consequences of the interventional procedures used to reach success cannot be understated.  Currently, over three-fourths of the patients who survive their childhood cancer for more than 40 years report the presence of either a severely debilitating, life-threatening complication or have died from a long-term complication arising from the therapeutic interventions.3,4 
It is reported that the leading cause of long-term mortality in this patient population is the development of a secondary or subsequent malignant neoplasm (SMN).1,2,4   In specific, approximately 20% of childhood cancer survivors will have developed an SMN by their 40th cancer free anniversary.4 Unfortunately, the risk of developing an SMN does not plateau with age, with the incidence continuing to rise as the length of follow-up increases.1,2,5 It is notable that the cancer-specific survival in a patient who develops an SMN is up to 40% lower than comparable individuals with a similar staged primary malignancy.4  This decrease in survivorship is believed to be due to one of three etiologies:  inherent genetic abnormalities within the patient that stimulate tumor development or growth,  prior chemo-radiation therapies inducing genetic resistance to treatment or a reduction in the potential types of treatment options available due to accumulative toxic effects from the prior therapies employed.3,4  Directly related to the limited effectiveness of chemoradiation therapy and the need to reduce the dosage of treatment regimens are the recommendations to screen the at-risk patient population, specifically, the earlier the tumor is diagnosed, the lower the tumor stage, the less aggressive the treatment and the higher the documented cancer-specific survival.4  

It is important to be aware of the fact that the risk of developing an SMN is unequally expressed among childhood cancer survivors, with the cost risk benefits of long-term screening found to be beneficial in five specific high-risk patient categories; 1)  In patients where there is a genetic predisposition for tumor development.  2) In individuals where a presumably benign post-treatment non-malignant mass is present, typically this a persistent post tumor mass in patients who have survived treatment for neuroblastoma or rhabdomyosarcoma. 3) In persons where the initial type of tumor is known to predispose to the development of SMN, specifically, if the initial tumor was retinoblastoma, Hodgkin's lymphoma, or any kind of sarcoma. 4)  In patients where chemotherapy was administered before two years of age.  In this patient population, it is believed that the high rate of cellular proliferation that is present in the young infant or child renders their cells more susceptible to treatment induced DNA damage. 5) In any patient undergoing radiation therapy there is an increased risk for SMN, be aware that the younger the age of radiation exposure the higher the risk. 4 Compliance with cancer screen protocols in these five high-risk patient populations is associated with almost half of the SMN being diagnosed at an earlier stage, resulting in a documented improvement in cancer-specific survival. 1,4,5

The question arises why educate urologists regarding the need for surveillance?  We became aware of the need to inform the urologic community regarding the benefits of long-term cancer surveillance when we surveyed 100 consecutive high-risk childhood cancer survivors seen in our transitional and adult urologic clinics.  These patients had been referred for treatment of infertility, erectile dysfunction, symptomatic hypotestosteronemia, lower urinary tract symptomatology or follow up of a urinary diversion, all were genitourinary complications arising from the treatment of their childhood tumors.  It is, however, significant that the prior history of childhood cancer survivorship was only noted at the time of the intake history and physical examination.  Out of 100 consecutive high-risk patients seen in the urology clinics, 50% had been lost to surveillance protocols.4  This finding underscores both the need of the urologist to be aware of the long-term urologic consequences of childhood chemo-radiation therapy and their need to be informed regarding the risk for SMN in this patient population.   The urologist's ability to identify the high-risk patient and re-establish this patient with physicians who are familiar with the needed long-term surveillance protocols may indeed be a lifesaving event. In the United States, information, where to refer these patients, may be found on the website associated with the National Children's Cancer Society long-term follow-up clinics


Written by: Douglas A. Husmann, MD, Pediatric Urologist, Department of Urology, Mayo Clinic, Rochester, MN, USA

References:

  1. Armenian SH, Kremer LC, Sklar C. Approaches to reduce the long-term burden of treatment-related complications in survivors of childhood cancer. American Society of Clinical Oncology Educational Book. pp 196-204, 2015.
  2. Hudson MM, Link MP, Simone JV. Milestones in the curability of pediatric cancers. J Clin Oncol. 32: 2391-7,2014.
  3. Landier W, Armenian SH, Lee J et al. Yield of screening for long-term complications using the children's oncology group long-term follow-up guidelines. J Clin Oncol.  30: 4401-8, 2012.
  4. Husmann, DA: Cancer screening in the pediatric cancer patient: a focus on genitourinary malignancies and why does a urologist need to know about this?  J of Pediatric Urology 2018. Doi.org/10.10.16/j.purol.2018.10.015
  5. Hudson MM, Mulrooney DA, Bowers DC et al. High-risk populations identified in Childhood Cancer Survivor Study investigations: implications for risk-based surveillance. J Clin Oncol. 27: 2405-14, 2009.
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