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ASCO 2018

ASCO 2018: Survivorship and Surveillance in Management of Germ Cell Cancer

Chicago, IL (UroToday.com) Christian Kollmannsberger, MD, gave an excellent talk on survivorship and long-term surveillance in the management of germ cell tumors (GCTs). All major types of cancer therapy can result in side effects that can impair well-being, physical and psychosocial functioning, and overall quality of life. These side effects may last long after the treatment ends. In GCTs the late effects affecting mortality do not show until 20+ years of follow-up.  Ironically, the mortality from long-term complications in good/intermediate risk patients may be higher than the mortality associated with the disease itself. In fact, 20 years after cisplatin-based chemotherapy, patients have a 50% higher risk of dying from unrelated GCT causes compared to the general population.[1]

Survivorship is divided into 4 distinct periods:

  1. Acute – from diagnosis to end of treatment
  2. Transitional – end of treatment period
  3. Extended – the first 5 years after end of treatment
  4. Permanent -  after the first 5 years from end of treatment. This includes the period when long-term/late toxicity arise and secondary malignancies develop
The essential components of survivorship care include recurrence and new cancers prevention, surveillance for cancer spread, intervention following consequences of cancer and its treatments, and coordination between specialist and primary care providers to ensure that all health needs are met. 

Some of the challenges of survivorship care include the fact that this a neglected phase of the cancer care trajectory. Survivors may be unaware of risks and have no follow-up plan. Furthermore, the healthcare providers themselves, lack education and training on survivorship, and there is a lack of specific guidelines pertaining long-term follow-up. 

Survivorship has many practical, and even more emotional issues (Figure 1,2).

Figure 1 – Practical issues of cancer survivorship:
practical issues survivorship

Figure 2 – Emotional issues of cancer survivorship:
emotional issues survivorship

There is a myriad of medical and psychosocial sequelae caused by GCT treatment (Figure 3). A partial list of such sequelae is provided below.

  1. GCT patients treated with cisplatin-based chemotherapy have an increased risk of developing metabolic syndrome.[2] 
  2. Cardiovascular morbidity and mortality are increased in these patients, typically developing years after treatment with either chemotherapy or radiotherapy. The combination of both these treatment modalities yields the highest risk. [3,4] 
  3. There is an increased risk of secondary malignancies, including bladder, kidney, thyroid, and other soft tissue cancers.[5] 
  4. Another potential sequala is nephrotoxicity caused by cisplatin damaging the proximal and distal tubular epithelium and collecting ducts. The cumulative dose of cisplatin is associated with the degree of renal function damage. 
  5. Ototoxicity can also occur, presumably caused by selective damage to the outer hair cells.  It includes tinnitus and hearing impairment, with a frequency of 20-40%, with approximately 20% persisting indefinitely.  The main risk factors for ototoxicity include pre-existing hearing impairment, previous significant noise exposure, hypophosphatemia, hypomagnesemia, and most importantly, cumulative cisplatin dose. Genetic polymorphisms contribute to the development of cisplatin-induced ototoxicity.  The SNP rs62283056, was the first intron of Mendelian deafness gene WFS1 that was found to be associated with ototoxicity.[6] Using this data, we can predict which patients are at higher genomic risk for developing ototoxicity. This will enable us to develop intervention strategies to mitigate hearing loss from cisplatin therapy.
  6. Neurotoxicity – expression of RPRD1B was associated with cisplatin-induced peripheral neuropathy. Long-term serum platinum levels are significantly associated with the severity of neurotoxicity 5-20 years after cisplatin-based chemotherapy.[7]
  7. Residual serum platinum has been detected decades following treatment. Long-term platinum has been associated with hypogonadism, hypercholesterolemia, hypertension, paresthesia, and other additional long-term toxicities.
  8. Hypogonadism may contribute to the development of metabolic syndrome, cardiovascular disease, depression, sexual dysfunction, fatigue and more.[8] If patients are symptomatic, they should testosterone replacement. 
Figure 3: Physical effects of testicular cancer treatment:
physical effects testicular cancer treatment

Dr. Kollmannsberger moved on and summarized the indications for survivorship care in GCT patients. Patients with GCTs treated with chemotherapy should be followed for life. The shared care model is preferred, in which oncology and primary care teams work together. In this model, early intervention is recommended to avoid secondary effects from late toxicity. 

Next, Dr. Kollmannsberger provided a list of measures in an attempt to improve survivorship in GCTs, which included :

  • Avoidance of overtreatment
  • Development of predictive biomarkers for recurrent disease to guide therapy
  • Determine the extent and frequency of long-term toxicity
  • Examine mechanisms of long-term toxicity and potential risk factors
  • Understand the molecular basis of various toxicities and adjust treatment to avoid long-term risk
  • Develop structured survivorship programs tailored to GCT survivors
  • Implement lifestyle changes and preventative measures
  • Treatment of late toxicity
Dr. Kollmannsberger concluded his excellent talk and emphasized that long-term toxicity impacts quality of life and life expectancy of GCTs survivors. Overtreatment must be avoided, as it is the best prophylaxis against long-term toxicity. Elucidation of underlying pathways will allow the development of targeted prevention, and intervention strategies to optimize risk-based care, minimize chronic morbidities, and improve patients’ quality of life. Structured survivorship care is required to minimize the impact of long-term toxicity on quality of life and mortality of GCT patients. Lastly, the treating physicians and GCT patients who are treated with chemotherapy must understand that they need to be followed for life.

References:
1. Lubberts et al. JCO 2017
2. Haugnes et al. Ann Oncol 2007
3. Huddart et al. JCO 2003
4. Haugnes et al. JCO 2010
5. Fung et al. JCO 2013
6. Wheeler et al.  Clin Cancer Res 2016
7. Dolan et al. Clin Cancer Res 2017
8. Bandak et al. Andrology 2016

Presented by: Christian Kollmannsberger, MD, University of British Columbia, Vancouver, Canada


Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, Twitter: @GoldbergHanan at the 2018 ASCO Annual Meeting - June 1-5, 2018 – Chicago, IL USA