By Dr Maxton Bergin
When skin cancer is treated without surgery, it can be difficult to know whether the area has fully responded. Redness, crusting, pigment change and scarring can all remain after radiotherapy or topical treatments such as imiquimod or 5-fluorouracil (5-FU). These changes may be part of normal healing, but they can also make it harder to judge whether any cancer remains.
Non-invasive skin imaging can provide extra information before, during and after treatment. It may include clinical examination, dermoscopy, standardised photography and reflectance confocal microscopy (RCM), sometimes called an optical biopsy. These tools allow doctors to document a lesion, compare it over time and look for features that may suggest treatment response or possible persistent disease.¹⁻³
However, imaging is not a guarantee that residual or recurrent tumour will be detected. A treated area that looks clear on examination or imaging is not always proven to be clear at a microscopic level. If a doctor remains concerned about persistent or recurrent skin cancer, a surgical biopsy may still be needed for histopathology—the laboratory examination of tissue removed during a biopsy.¹⁻⁴
What is non-invasive skin cancer treatment monitoring?
Non-invasive skin cancer treatment monitoring means checking a treated lesion without immediately removing more tissue. It combines clinical review with images taken before, during or after treatment so doctors can compare the same area over time.¹˒²
The approach may be used after:
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radiotherapy;
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topical imiquimod, an immune-response-modifying cream;
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topical 5-fluorouracil (5-FU), a cream used for sunspots and, in selected circumstances, squamous cell carcinoma in situ (also called Bowen disease);
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photodynamic therapy, where a light-sensitive treatment is activated with a specialised light source;
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other carefully selected non-surgical or minimally invasive treatments.²˒⁵˒⁶
The appropriate follow-up method depends on the original diagnosis, tumour subtype, location, treatment used and the patient’s individual risk factors.²˒⁵˒⁶
Why treated skin can be difficult to assess
A treatment response is not always obvious from looking at the skin. Radiotherapy and topical treatments are intended to create a visible reaction in many patients. During and after treatment, the area may become red, inflamed, scaly, crusted, lighter or darker than the surrounding skin, or develop scar-like changes.¹˒²˒⁵
These changes can obscure the original lesion. For example, inflammation after imiquimod can be expected and may indicate that the immune system is responding to the treatment, but inflammation alone does not confirm that all abnormal cells have been removed.¹˒⁷ Similarly, a radiotherapy-treated area may remain discoloured or firm long after treatment, making clinical assessment more complex.⁸˒⁹
This is where serial imaging can be useful. A baseline image before treatment and repeat images after treatment can help the treating doctor identify whether the area is settling as expected, remaining unchanged or developing features that need further investigation.¹˒²˒⁸
The role of clinical examination
Clinical examination remains the foundation of treatment monitoring. Your treating doctor assesses the site in person, asks about symptoms such as bleeding, tenderness, itch or a non-healing area, and compares the treated site with previous photographs.²˒⁵
No imaging method can replace the importance of examining the skin directly. Some features—such as ulceration, a new lump, a change in sensation or rapid growth—may prompt a biopsy even if previous imaging was reassuring.²˒⁵˒⁶
For this reason, imaging should be understood as an additional source of information rather than a stand-alone answer.
Dermoscopy and digital photography
Dermoscopy
Dermoscopy is a close-up examination using magnification and specialised light. It allows doctors to see skin structures that are not visible to the naked eye, including pigment patterns, blood vessels and surface features.³˒¹⁰
When a lesion has been treated, dermoscopy may help document changes in these structures and identify areas that need closer assessment. It is quick, painless and can be repeated at follow-up visits.³˒¹⁰
Dermoscopy has limitations after treatment. Inflammation, pigmentation and scarring may alter the appearance of the skin and make some features harder to interpret. Therefore, dermoscopy findings are considered alongside the clinical history, treatment timing and, where appropriate, other imaging or biopsy.¹˒²˒³
Standardised digital photography
Standardised photography creates a visual record of the treated area. For people with multiple lesions or broad areas of sun damage, this can help document the original treatment field and support comparison at later appointments.¹˒²
Photography does not show cells or deeper structures, but it can be valuable for noticing visible change, tracking the healing pattern and ensuring that the same area is assessed consistently over time.¹˒²
What is reflectance confocal microscopy?
Reflectance confocal microscopy, or RCM, is a non-invasive imaging technique that uses a low-power laser to create highly magnified images of the layers of the skin. It is sometimes called an optical biopsy because it can show cellular patterns without cutting the skin.¹˒³˒¹¹
During an RCM examination, a small imaging head is placed gently against the skin. The clinician captures images at several levels through the epidermis and upper dermis. The procedure does not involve needles, incisions or stitches.¹˒³˒¹¹
RCM is particularly suited to lesions located in cosmetically sensitive areas, including the face. It can be useful when a treated site is difficult to assess because of residual redness, pigment changes or scarring.¹˒³˒¹¹
How confocal microscopy may help after treatment
RCM may provide additional information in selected cases by showing whether the upper skin layers have returned towards a more normal appearance or whether there are features that raise concern for persistent or recurrent disease.¹˒²˒⁷
Research has evaluated RCM for monitoring non-surgical treatment of basal cell carcinoma, actinic keratosis and squamous cell carcinoma in situ, including treatment with imiquimod, 5-FU, photodynamic therapy and other approaches.¹˒²˒⁷˒¹² A recent systematic review found that RCM could help assess treatment response and identify possible subclinical disease, especially where treatment-related inflammation makes ordinary clinical assessment difficult.¹
Imaging after radiotherapy
Radiotherapy is an established option for selected skin cancers, particularly where surgery is unsuitable, declined or likely to cause substantial functional or cosmetic impact.⁵˒⁶ It may be used for some basal cell carcinomas, squamous cell carcinomas and selected cases of lentigo maligna, depending on the diagnosis and multidisciplinary treatment plan.⁵˒⁶˒⁸
After radiotherapy, the skin can remain red, dry, scaly, darker or lighter than normal, and may develop longer-term texture changes. These effects can make it challenging to distinguish normal treatment response from persistent disease through visual examination alone.⁸˒⁹
Clinical follow-up is essential. In selected cases, dermoscopy, photography and RCM can provide a baseline and help document changes over time. RCM may show radiation-related inflammation and structural change as well as features that warrant further investigation, but a suspicious site may still need biopsy.⁸˒⁹
Imaging after imiquimod
Imiquimod is a prescription cream that stimulates a local immune response. It may be used for selected superficial basal cell carcinomas, actinic keratoses and other conditions where it is clinically appropriate.⁵˒⁶
Redness, irritation, crusting and inflammation are common during treatment. These reactions can be uncomfortable, but they are not a reliable measure of whether the lesion has completely cleared.⁷˒¹³
Before treatment, imaging may document the lesion’s size, borders and internal features. At follow-up, the doctor may compare new dermoscopic or confocal images with the baseline to assess whether concerning features have resolved or whether there are areas that need closer review.¹˒⁷˒¹³
Small studies and case series suggest RCM can sometimes identify features of residual basal cell carcinoma in areas that appear clinically clear after imiquimod.¹˒⁷ However, this does not mean every treated lesion requires RCM, nor does it mean RCM can replace biopsy when there is ongoing concern.¹˒³˒⁴
Imaging after 5-fluorouracil treatment
Topical 5-FU is commonly used for actinic keratoses, also known as sunspots, and may be used in selected cases of squamous cell carcinoma in situ.⁶˒¹⁴ It causes inflammation in abnormal sun-damaged skin, often resulting in redness, scaling and crusting during treatment.⁶˒¹⁴
Clinical examination and photography are commonly used to assess the response. RCM has also been studied for monitoring actinic keratoses and may detect features of both clinically visible and less obvious disease, but the role of RCM depends on the site, diagnosis and available expertise.¹˒¹²
A persistent, thickened, tender, bleeding or non-healing area after treatment should be reviewed promptly. It may need dermoscopy, further imaging or biopsy, depending on the clinical assessment.⁶˒¹⁴
When non-invasive imaging may be particularly useful
Non-invasive imaging may provide helpful additional information when:
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a lesion is on the face or another cosmetically sensitive area;
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a lesion was treated without surgical removal;
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redness, inflammation, pigment change or scarring makes the treated site difficult to assess;
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a baseline is needed before treatment for later comparison;
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the doctor wants to compare an area at planned intervals;
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the full extent of a lesion needs assessment before treatment;
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there is concern about persistent or recurrent disease, but the need for biopsy is not yet clear.¹˒³˒⁸˒¹¹
Suitability is always individual. The same imaging approach is not right for every lesion, cancer type or treatment pathway.
Can imaging prove a skin cancer has gone?
No. Imaging can provide reassuring information, but it cannot guarantee microscopic clearance or rule out recurrence in every situation.¹˒³˒⁴ A lesion may look clinically clear while small areas of disease remain, and treatment-related changes can sometimes mimic disease on imaging.¹˒⁷˒⁸
Histopathology—the laboratory examination of tissue removed during a surgical biopsy—remains necessary when a definitive tissue diagnosis is required.³˒⁴ If a treating doctor suspects residual or recurrent tumour, biopsy or further treatment may be recommended regardless of previous imaging.
How Skintel supports treatment monitoring
Skintel is a specialist diagnostic skin imaging service. It does not provide radiotherapy or prescribe topical skin cancer treatments. Instead, Skintel can provide advanced imaging and medical interpretation to support the treating doctor’s decision-making.
Where appropriate, Skintel may use dermoscopy, digital photography and reflectance confocal microscopy to document a lesion before treatment or assess a treated area over time. Findings are reviewed by a skin cancer doctor and communicated in a report to the referring clinician.
Your GP, dermatologist, surgeon or radiation oncologist remains responsible for treatment decisions, follow-up intervals, biopsy and ongoing management. Imaging adds information to that care pathway; it does not replace clinical judgement or histopathology when these are needed.
Frequently Asked Questions
Can imaging tell if skin cancer treatment has worked?
Imaging can provide useful evidence of treatment response, but it cannot prove in every case that all cancer cells have gone. Clinical examination, dermoscopy, photography and RCM may help compare the treated area over time and identify features that need further investigation.¹˒² If residual or recurrent disease is suspected, biopsy may still be needed for histopathology—the laboratory examination of tissue removed during a biopsy.³˒⁴
Can confocal microscopy detect skin cancer after treatment?
Confocal microscopy may help identify features that raise concern for persistent or recurrent skin cancer in selected treated areas, particularly when redness, pigmentation or scarring makes ordinary examination difficult.¹˒²˒⁷ It is an additional diagnostic tool, not a guarantee of clearance. ³˒⁴˒¹¹
Do I still need a biopsy after topical treatment?
You may still need a biopsy after topical treatment if the treated area remains suspicious, fails to heal as expected, changes again or shows concerning features on examination or imaging.⁵˒⁶ Biopsy provides histopathology, which examines removed tissue under a microscope and remains the standard method for confirming many diagnoses.³˒⁴ A clear-looking treatment site does not always prove microscopic clearance.
How is a skin cancer monitored after radiotherapy?
Skin cancer after radiotherapy is monitored with planned clinical follow-up, and may also involve dermoscopy, photography or selected non-invasive imaging.⁵˒⁶ The treating team assesses healing, skin changes and any signs that could suggest persistent or recurrent disease. Radiation-related redness, pigment changes and scarring can make assessment difficult, so a suspicious area may need biopsy after discussion with the treating radiation oncologist.⁶˒⁸˒⁹
Can skin cancer come back after imiquimod?
Yes. Skin cancer can persist or recur after imiquimod, particularly if treatment is not suitable for the lesion type or if microscopic disease remains.⁵˒⁶ Most treatment failures in studies of imiquimod for superficial basal cell carcinoma occurred within the first year, which is why follow-up remains important.⁶ Imaging may support review, but persistent or recurrent disease needs clinical assessment and sometimes biopsy.
What does an optical biopsy show?
An optical biopsy, usually reflectance confocal microscopy, shows highly magnified images of the cells and structures in the top layers of living skin without cutting it.³˒¹¹ It can help doctors assess whether a lesion has features that appear reassuring or concerning, and it can be repeated to compare an area over time. It cannot replace biopsy when tissue is needed to confirm diagnosis.³˒⁴
Can confocal microscopy replace a surgical biopsy?
No. Confocal microscopy is a useful non-invasive adjunct, but it does not replace surgical biopsy when a definitive diagnosis, tumour depth assessment or histopathology is clinically required.³˒⁴˒¹¹ It can be affected by inflammation, scarring and the characteristics of the lesion. Your treating doctor decides when biopsy is the safer and more appropriate next step.
Why does treated skin still look red or scaly?
Redness, scaling, crusting and pigment changes can be normal effects of radiotherapy, imiquimod or 5-FU treatment.⁵˒⁶˒¹³˒¹⁴ These treatments can cause inflammation as they act on abnormal skin cells. However, persistent symptoms or a new change should be reviewed by your treating doctor, because appearance alone cannot always distinguish normal healing from residual or recurrent disease.
Conclusion
Non-invasive skin cancer treatment monitoring combines clinical examination with tools such as dermoscopy, photography and reflectance confocal microscopy. These technologies can help document a lesion before treatment, assess changes over time and provide additional information when healing, inflammation or scarring makes a treated site difficult to interpret.
They are not replacements for careful clinical follow-up, biopsy or histopathology when these are needed. For patients treated with radiotherapy, imiquimod, 5-FU or other non-surgical approaches, the right monitoring plan depends on the individual lesion, diagnosis, treatment and personal risk profile.
If your treating doctor believes advanced imaging may add useful information, Skintel can provide a diagnostic assessment and report to support your ongoing care.
Disclaimer
All information is general and not intended as a substitute for professional advice.
References
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Moscarella E, Rabinovitz H, Zalaudek I, et al. Monitoring the effectiveness of noninvasive or minimally invasive therapies for nonmelanocytic lesions using reflectance confocal microscopy: a systematic review. Actas Dermosifiliogr. 2026;117(2):101-112.
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Ulrich M, Lange-Asschenfeldt S, Gonzalez S. The use of reflectance confocal microscopy for monitoring response to imiquimod treatment of basal cell carcinoma. Br J Dermatol. 2012;167(5):1173-1175.
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Longo C, Ragazzi M, Rajadhyaksha M, et al. Reflectance confocal microscopy: an effective tool for diagnosing melanoma and non-melanoma skin cancers. J Am Acad Dermatol. 2018;79(2):247-257.
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Dinnes J, Bamber J, Chuchu N, et al. Reflectance confocal microscopy for diagnosing keratinocyte skin cancers in adults. Cochrane Database Syst Rev. 2018;12(12):CD013191. doi:10.1002/14651858.CD013191.
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Peris K, Fargnoli MC, Garbe C, et al. European consensus-based interdisciplinary guideline for diagnosis and treatment of basal cell carcinoma—update 2023. Eur J Cancer. 2023;192:113254. doi:10.1016/j.ejca.2023.113254.
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Venturini M, Gualdi G, Zanca A, et al. Assessment of changes in lentigo maligna during radiotherapy by in-vivo reflectance confocal microscopy: a pilot study. Br J Dermatol. 2015;172(1):81-87.
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Ruiz ES, et al. Radiation therapy for synchronous basal cell carcinoma and lentigo maligna: monitoring response with reflectance confocal microscopy. Case Rep Dermatol Med. 2015;2015:1-6.
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Kittler H, Pehamberger H, Wolff K, Binder M. Diagnostic accuracy of dermoscopy. Lancet Oncol. 2002;3(3):159-165.
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Dickman AM, et al. Reflectance confocal microscopy: principles, basic terminology, clinical indications, limitations, and practical considerations. J Am Acad Dermatol. 2021;84(1):1-15.
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Ulrich M, Maltusch A, Rius-Diaz F, et al. Clinical applicability of in vivo reflectance confocal microscopy for the assessment and monitoring of actinic keratoses and treatment response. Br J Dermatol. 2008;158(2):273-280.
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Cancer Council Australia. Topical treatments for skin cancer. Sydney: Cancer Council Australia; 2024.
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Cancer Council Australia. 5-fluorouracil for actinic keratoses and Bowen disease. Sydney: Cancer Council Australia; 2024.


