13. Follow-up after treatment for keratinocyte cancer

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Clinical practice guidelines for keratinocyte cancer > 13. Follow-up after treatment for keratinocyte cancer


Background

There are three reasons to undertake follow-up for patients who have been treated for keratinocyte cancer (KC):

  • to identify new lesions
  • to identify recurrent lesions
  • to identify metastatic disease.

Several studies have reported the higher incidence of subsequent KC following an index case.[1][2]

The frequency and duration of review for patients who have undergone treatment for a KC will be determined by the location of the original lesion, the original histopathology findings, the histological margin of the original lesion, the method of treatment of the original lesion and the number of previous KCs.

At each follow-up visit, all of the skin surface that has been chronically or intermittently sun-exposed should be examined. Good lighting is important. Visual examination (both with and without magnification) should be followed by appropriate physical examination, where needed, for signs such as induration and tenderness.

There is a lack of evidence to guide recommendations on follow-up after treatment for KC. No study has assessed the possible benefit from regular medical review for patients who have been treated for KCs, compared with observation by the patients themselves.

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Overview of evidence (non-systematic literature review)

Lesion-related factors associated with higher risk of recurrence include certain subtypes and sites (Table 5).[3]

Table 5. Tumour-specific factors associated with recurrence of keratinocyte cancers

Tumour type Normal risk High risk
Basal cell carcinoma Nodular subtype

Nodulocystic subtype

Superficial subtype

Fibroepithelioma  subtype

Infiltrative subtype

Sclerosingscar-like (morphoeic) (morphoeic) subtype

Micronodular subtype

Basosquamousshowing evidence of squamatisation (descriptor applicable to basaloid tumours and indicating aggressive subtype) carcinoma

Recurrence

Cutaneous squamous cell

carcinoma

In situ subtype

Well-differentiated subtype

Moderately well-differentiated subtype

Location on area other than head and neck

Poorly differentiated subtype

Adenosquamous subtype

Spindle cell subtype

Increasing thickness of the primary tumour

Location on the head and neck especially the lip, ear and genitalia

Origin in a burn scar

Recurrence

Recurrence of basal cell carcinoma

Approximately 44% of people will develop a second basal cell carcinoma (BCC) within 3 years of a BCC excision.[1] This represents a 10-fold increase, compared with the general population.

Local recurrence is rare (<2%)[2] after histological clearance, with most local recurrences occurring within 2 to 3 years, but up to 20% may occur within 5–10 years.

Regional recurrence is extremely rare. Clinical assessment for regional recurrence is unnecessary, except in those with significant immunosuppression or genetic syndromes associated with increased risk of metastases.

Recurrence of cutaneous squamous cell carcinoma

Overall, the 3-year cumulative risk of a subsequent cutaneous squamous cell carcinoma (cSCC) after an index cSCC is 18%; at least a 10-fold increase in incidence, compared with the incidence of first tumours in a comparable general population.[1]

Local recurrence is uncommon after wide excision, but the risk of recurrence increased in the presence of risk factors including certain anatomical sites, certain subtypes, and perineural invasion (PNI), for a tumour in a previously treated site, and for a recurrent lesion (versus primary lesion) (see: Surgical treatment).[1] Most local recurrences occur within 2–3 years.

Regional recurrence is uncommon and usually occurs in patients with risk factors for local recurrence (including tumour sites of lip, ear or genitalia) and in certain groups. Recurrence is usually within 2 years.

A systematic review and meta-analysis of 36 studies (17,248 patients with 23,421 cSCCs) of low-to-moderate quality identified the following risk factors for recurrence of cSCC, in descending order of risk ratio (RR):[3]

  • Breslow thickness >2mm (RR 9.64; 95% confidence interval [CI] 1.30–71.52)
  • invasion beyond subcutaneous fat (RR 7.61; 95% CI, 4.17–13.88)
  • Breslow thickness >6mm (RR 7.13; 95% CI 3.04–16.72)
  • PNI (RR 4.30; 95% CI 2.80–6.60)
  • diameter >20mm (RR 3.22; 95% CI 1.91–5.45)
  • location on the temple (RR 3.20; 95% CI 1.12–9.15)
  • poor differentiation (RR 2.66; 95% CI, 1.72–4.14).

Risk factors for metastasis were:[3]

  • invasion beyond subcutaneous fat (RR 11.21; 95% CI 3.59–34.97)
  • Breslow thickness >2mm (RR 10.76; 95% CI, 2.55–45.31)
  • Breslow thickness >6mm (RR 6.93; 95% CI, 4.02–11.94)
  • diameter >20mm (RR 6.15; 95% CI, 3.56–10.65)
  • poor differentiation (RR 4.98; 95% CI 3.30–7.49)
  • PNI (RR 2.95; 95% CI 2.31–3.75)
  • immunosuppression (RR 1.59; 95% CI 1.07–2.37)
  • location on the temple (RR 2.82; 95% CI 1.72–4.63)
  • location on the ear (RR 2.33; 95% CI 1.67–3.23)
  • location on the lip (RR, 2.28; 95% CI 1.54–3.37).

Risk factors for cancer-specific death were:[3]

  • diameter >20mm (RR 19.10; 95% CI 5.80–62.95)
  • poor differentiation (RR 5.65; 95% CI 1.76–18.20)
  • location on the ear (RR 4.67; 95% CI, 1.28–17.12)
  • location on the lip (RR, 4.55; 95% CI 1.41–14.69)
  • invasion beyond subcutaneous fat (RR 4.49; 95% CI 2.05–9.82)
  • PNI (RR 4.06; 95% CI 3.10–5.32).

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Follow-up

Following treatment of a primary KC or related tumour, all patients need to receive counselling about their risk for further primary tumours, local persistence of their previous primary tumour and for metastatic disease, where appropriate. As much as possible these risks should be quantified. The patient should be advised about ways in which these problems might present, any signs or symptoms they should look for, and when medical assessment is needed.

In addition, patients should be advised about prevention strategies (e.g. ultraviolet radiation protection strategies and chemoprevention, including nicotinamide for patients with multiple previous KCs), and Vitamin D intake (see: Prevention of keratinocyte cancer [UV protection strategies, chemoprevention and vitamin D]).

It is appropriate for specialists to return patients to their referring general practitioner (GP) for ongoing care when their treatment is complete. The time of return will depend on the individual's lesion, type of treatment, and on agreement between the specialist and the referring GP.

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Future research

As more information about testing for specific genetic markers in KC becomes available, affected patients with genetic markers may require specific, yet unknown, follow-up regimes.

Practice Points

Practice pointQuestion mark transparent.png

PP 13.1.1. For patients who have undergone non-surgical treatments, where histological evidence of clearance is not available, planned regular follow-up (not just reassessment prompted by clinical need) should be provided for up to 3 years. Examination includes a full skin check for new lesions as well as inspection of the site of the original lesion.

Practice pointQuestion mark transparent.png

PP 13.1.2. For patients with cutaneous squamous cell carcinoma that is moderately to poorly differentiated or occurs on the lip or ear, initial follow-up should be conducted at 3 months and then every 6 months. It should always include examination of the draining lymph node basin.

Key point(s)
  • For patients with histological clearance of primary keratinocyte cancers and low-risk tumours, such as basal cell carcinomas and well-differentiated cutaneous squamous cell carcinomas, no specific evidence-based follow-up scheme is recommended.
  • All patients with a previous skin cancer should be advised to undergo annual skin examination for life, as part of routine health checks by their health care provider, to look for the development of new lesions.
  • Patients should be offered counselling about their risk for further primary tumours, local persistence of their previous primary tumour and for metastatic disease.
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Health system implications

Clinical practice

Implementation of the guidance on follow-up of KC would not alter current clinical practice.

Resourcing

Performing effective skin examinations, including dermatoscopy, requires adequate training and experience (see: The role of primary care in the prevention and management of keratinocyte cancer). In primary care, primary care nurses can undertake patient education about protection from UV radiation.

Barriers to implementation

No barriers to the implementation of this guidance are envisaged.

Discussion

Unresolved issues

Unlike for some other cancer types, there are no standardised protocols for surveillance (including monitoring strategies and intervals) after treatment of KC.

Studies currently underway

None.

Future research priorities

As more information about testing for specific genetic markers in KC becomes available, affected patients with genetic markers may require specific, yet unknown, follow-up regimens. Combining evidence for all known predictors might enable clinicians to choose a tailored follow-up strategy taking that better matches an individual’s absolute risk of recurrence or other adverse outcomes,

References

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