Management of Skin Malignancies: Lessons Learnt at a Tertiary Care Center in Northern India
Corresponding Author: Santosh Irrinki, Department of General Surgery, PGIMER, Chandigarh, India, e-mail: firstname.lastname@example.org
Introduction: The prognosis of skin cancers in India is worse when compared to the Western countries. It may be because of overall rarity and low experience at individual centers, presentation with advanced disease, inadequate first treatment and a higher incidence of poor prognostic disease subtypes.
Aims and objectives: To analyze the clinicopathological characteristics, recurrence patterns and the completeness of first treatment in the patients with skin cancers.
Materials and methods: It was a retrospective analysis of all patients operated for skin cancers. Mean and SD was computed for normal data; for skewed data, median and IQR were used. Kaplan-Meier analysis was used to assess the survival.
Results: There were 18 cases of skin malignancies of which 8 (44.4%) patients had MM 5 (27.8%) had SCC 2 (11.1%) each had BCC and DMFSP and 1 (5.6%) had MCC. Pain was the most common presenting symptom (55.6%). The median follow-up was 12.25 months (Range 2–21.5 months). Ten (55.6%) patients had received a primary treatment elsewhere, not in accordance with the standard treatment guidelines. The median delay between the primary treatment and definitive surgery was 8 months (Range 2.5–48 months) which led to an increase in surgical morbidity in at least 4 (40%) of these patients. Median disease-free survival in the study was 12 months.
Conclusion: Skin cancers have poor outcomes in Indian patients when compared to the Western countries. Awareness programs for early diagnosis, a high index of suspicion and early referral to a center experienced in handling these malignancies may help in improving outcomes.
How to cite this article: Khare S, Singh A, Singhai P, et al. Management of Skin Malignancies: Lessons Learnt at a Tertiary Care Center in Northern India. J Postgrad Med Edu Res 2022;56(2):63-69.
Source of support: Nil
Conflict of interest: None
Keywords: BCC, DMFSP, Melanoma, Merkel cell carcinoma, SCC, Skin cancer
Skin cancers are a heterogeneous group of cancers classified into melanoma and nonmelanoma skin cancers (NMSC) and have a highly varied incidence across the globe.1 Melanoma of the skin, with 14,260 cases,2 is the 3rd most common cancer in Australia (apart from NMSCs). Australia also gets around 767,000 cases of NMSCs per year.3 In the US, melanoma of the skin ranks 7th in incidence with 71,343 cases4 whilst the approximate number of cases of NMSCs is in excess of 3.5 million.3 In contrast, in India, melanoma is the 33rd most common malignancy with only 3048 cases (the incidence of NMSCs is unknown).5
Although malignant melanoma (MM) has a poorer prognosis when compared to the two most common varieties of NMSCs, namely basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) which account for almost 99% of NMSCs,1 many other rarer varieties of NMSCs like Merkel cell carcinoma (MCC), cutaneous T-cell lymphoma, Kaposi Sarcoma and angiosarcoma are also associated with poor prognosis.6-9
In India, skin cancers pose some peculiar problems. Because of overall rarity, experience at individual surgical centers is low and even at high volume referral centers, they form about 0.5–2.4% of all cancers being operated upon.10,11 Another problem is that many patients present with advanced malignancy, and even in resectable cancers, almost 42% are locally advanced.10 Yet another problem is of primary treatment of the tumors in nonspecialized centers as 31.1–100% patients presenting to a referral surgical unit have undergone an excision elsewhere, making accurate staging and treatment difficult.10,11 In addition, it may also lead to a delay in definitive therapy viz wide excision, lymph node sampling, radiotherapy and systemic therapy. Furthermore, the Acral Lentiginous variety of MM, which is associated with poor prognosis, is relatively more common in the Indian population.12 It may be because of the combination of these factors that although, the number of patients with MM detected in India in 2018 was 3048, the number of deaths related to it in the same year was 2053.5 This assumes greater importance when we compare it to western countries (MM in Australia in 2018: new cases-14260, deaths-1602, MM in the US in 2018: new cases-71343, deaths-9491).2,4
Worried about all these anomalies in skin cancer management in India, we performed this analysis to probe the clinicopathological characteristics and short-term recurrence patterns of skin cancers and the completeness of the first treatment of the patients with skin cancer.
MATERIALS AND METHODS
This was a retrospective analysis. After the institutional ethics committee approval, data were collected from perioperative records and from follow-up visits for all the patients who were operated on for skin cancers in our unit over the 1-year period from 15th March 2019 to 14th March 2020. Any patient with pre-existing metastases were excluded from the study. Records were also checked for any previous treatment received which was then compared to the standard treatment guidelines (NCCN®)13-17 at the time of that treatment. The staging was done according to AJCC 8th edition13-17 (Extrapolated for cutaneous SCC from cutaneous SCC of head and neck). Disease-free survival (DFS) and overall survival (OS) were defined as the time interval between surgery and any event (detection of local or systemic recurrence) or death, respectively.
Data analysis was done using SPSS ver22. Mean and SD was computed for normally distributed data whereas, for skewed data, median and IQR were used. Kaplan-Meier analysis was performed to estimate the DFS and OS.
Eighteen cases of skin cancers were operated in our unit during the study period. No patient was lost to follow up. The median follow-up was 12.3 months. Overall, 4 patients also had associated co-morbidities; 1 patient with MM had hypothyroidism, controlled on oral Thyroxine, 1 patient with BCC was hypertensive controlled with oral medications and 2 patients with SCC had both diabetes and hypertension which were again controlled with oral medications and perioperative insulin therapy.
The clinicopathologic characteristics of the patients can be found in Table 1. All the patients operated on had nonmetastatic disease. Pigmentation was the most common symptom present in the patients with MM (7, 87.5% patients). However, most of the patients with MM took medical advice because of either pain (5 patients, 62.5%), regional nodal mass (4 patients, 50%) or both. Four (50%) patients with MM had Tx disease and the rest had T4 disease. All the patients in whom primary was excised by us had acral lentiginous type of melanoma. In one patient, a biopsy that was reported elsewhere showed blue nevus but showed MM after slide review. Like MM, although ulcer was the most common symptom (5 patients, 100%) in patients with SCC, most (4 patients, 80%) presented only when there was associated pain. All 5 patients with SCC had some associated risk factor for the development of SCC; 4 (80%) patients had burn scar whereas 1 (20%) had actinic keratosis and a personal history of SCC. In three (60%) of the SCC patients, preoperative biopsy showed chronic inflammation without any evidence of malignancy and SCC was confirmed only after excision. One (20%) of the patient with SCC had T4, 3 (60%) had T3 whereas 1 (20%) had Tx disease. In patients with BCC, DMFSP and MCC, the subcutaneous nodule was the presenting symptom although 1 (50%) patient with BCC also had ulceration. One patient with BCC had a residual tumor <1 mm in size whereas the other one had no residual tumor (in both, primary excision was done elsewhere). The median size of tumors in DMFSP patients was 7 cm (Range 4–10 cm). The size of the tumor of the MCC patient was 7.5 cm.
|No. of patients||8 (44.4%)||5 (27.8%)||2 (11.1%)||2 (11.1%)||1 (5.6%)||18 (100%)|
|Age (in years) (Mean ± SD, Range)||45.5 ± 17.7 (21-82)||54.4 ± 12.1 (45-79)||54.5 ± 17.7 (42-67)||42.5 ± 7.8 (37-48)||47||48.7 ± 14.4 (21-82)|
|Female sex||3 (37.5%)||2 (30%)||0 (0%)||2 (100%)||1 (100%)||8 (44.4%)|
|Duration of symptoms in months (median, IQR, range)||27 (57; 3-120)||18 (12; 12-216)||27 (9; 18-36)||24 (12; 12-36)||10||18 (24; 3-216)|
|Location of primary|
|Head and neck||2 (100%)||2 (11.1%)|
|Trunk||2 (100%)||1 (100%)||3 (16.7%)|
|Lower limb||6 (75%)||5 (100%)||11 (61.1%)|
|Upper limb||2 (25%)||2 (11.1%)|
|Ulcer||3 (37.5%)||5 (100%)||1 (50%)||9 (50%)|
|Nodule||1 (12.5%)||2 (100%)||2 (100%)||1 (100%)||6 (33.3%)|
|Pigmentation||7 (87.5%)||7 (38.9%)|
|Axillary/inguinal/neck mass||4 (50%)||1 (20%)||5 (27.8%)|
|Pain||5 (62.5%)||4 (80%)||1 (50%)||10 (55.6%)|
|Presence of risk factors for development of skin cancer**||0 (0%)||5 (100%)||0 (0%)||0 (0%)||0 (0%)||5 (27.8%)|
|Follow-up in months (median, IQR, range)||14.8 (4.8, 3.5-21.5)||10.5 (1.5; 2-12.5)||11.5 (0.5, 11-12)||13.5 (0.75, 12-15)||14||12.25 (5.3; 2-21.5)|
*some patients had more than one symptom at presentation
**Apart from sun exposure
Outcomes of surgical procedures can be seen in Table 2. In patients with MM, 1 patient had undergone great toe amputation elsewhere with no doubt about the margin. Three patients with MM had clinically negative nodes (cN0). Out of them, 2 underwent sentinel lymph node biopsy (SLNB) procedure and 1 had to undergo a prophylactic regional nodal dissection because of unavailability of radioactive tracer on the day of surgery. All the 3 patients had negative nodes (pN0) on histopathology report (HPR). Rest five MM patients had clinically involved regional lymph nodes and underwent a therapeutic regional nodal dissection. Out of them, 3 (37.5%) had pN3 disease and 2 (25%) had pN2 disease. In contrast, only 1 (20%) patient with SCC needed therapeutic LN dissection, which, on HPR, came out to be positive (pN2a). Rest 4 patients had cN0 disease. The patient with MCC had cN0 disease and after SLNB was found to be pN0.
|Surgical procedure for primary**|
|Wide local excision with primary closure||3 (37.5%)||2 (100%)||1 (100%)||6 (33.3%)|
|Wide local excision with secondary intention healing||1 (20%)||1 (5.6%)|
|Wide local excision with SSG/Flap cover||3 (37.5%)||2 (40%)||2 (100%)||7 (38.9%)|
|Amputation (limb/digit)||1 (12.5%)||1 (20%)||2 (11.1%)|
|Patients with any margin positive||0 (0%)||0 (0%)||0 (0%)||0 (0%)||0 (0%)||0 (0%)|
|Management of regional lymph nodes|
|SLNB||2 (25%)||1 (100%)||3 (16.7%)|
|Regional lymph node dissection||6 (75%)||1 (20%)||7 (38.9%)|
|Morbidity (> 28 days)||3 (37.5%)||3 (60%)||0 (0%)||0 (0%)||0 (0%)||6 (33.3%)|
*There was no perioperative mortality
**In some patients, primary had already been excised outside. They were managed with either re-excision of the scar if there was doubt about the margins or left as it was
There were 4 patients with MM, 3 with SCC, 2 with BCC and 1 with DMFSP who underwent primary treatment elsewhere which was not in accordance with the standard guidelines (Table 3). In all the MM patients in this group, regional lymph nodes were not addressed and in 3, margins were doubtful. In the patients with SCC in this group, 1 patient underwent SSG without excision of primary, in another WLE with SSG was done for the primary but nothing for cN2 disease and another patient, despite being a good surgical candidate, was referred for radiotherapy. Both patients with BCC and 1 patient with DMFSP had undergone local excision without adequate margins.
|No. of patients||4 (50%)||3 (60%)||2 (100%)||1 (50%)||10 (55.6%)|
|Type of treatment received|
|Surgery||4 (100%)||2 (66.7%)||2 (100%)||1 (100%)||9 (90%)|
|Radiotherapy||1 (33.3%)||1 (10%)|
|Duration between primary treatment and definitive treatment in months (median, IQR, Range)||8 (2.8; 6-11)||11 (22.8; 2.5-48)||5 (0.5; 4.5-5.5)||14||8 (5.4; 2.5-48)|
|Increase in morbidity due to delay||1 (25%)||3 (100%)||0 (0%)||0 (0%)||4 (40%)|
*Patient with Merkel cell carcinoma did not receive any primary treatment before being referred to us
During follow-up, 9 (50%) patients developed recurrence (4 with MM, 4 with SCC and 1 with MCC) and 3 (16.7%) died (2 with MM and 1 with SCC). The median DFS for the patients with MM was 12 months, for the patients with SCC was 5.5 months and for the patient with MCC was 7 months. In patients who received primary treatment elsewhere, the median DFS was not significantly different from those who had either not received any primary treatment elsewhere or had received adequate treatment elsewhere (p = 0.730).
Skin malignancies are superficial malignancies and are accessible for early diagnosis and early treatment. Despite this, we found out that the median duration of symptoms in our patients was 18 months. As a result, most of our patients present at an advanced stage. In stark contrast to Western countries, where more than 90% of the patients present with localized MM (stages 1 or 2)18 having a median DFS of 68 months, 62.5% patients with MM in our study had clinically apparent metastases to regional lymph nodes in which the median DFS is a dismal 16 months.19 Similarly for SCC, in a study from MD Anderson Cancer Centre, TX, USA, only 15.5% patients had deep invasion beyond subcutaneous tissue20vis a vis at least 80% in our study (1 patient in our study had excision of primary elsewhere). The size of primary of both DMFSP and MCC was higher as well than reported in western literature (median size of DMFSP: 7 cm vs 2.9 cm;21 size of MCC: 7.5 cm vs average of 2.9 cm).22
Because of the advanced disease at the time of presentation, our patients had poor DFS as well. The DFS of 12 months in MM patients in our study is similar to that in another study from India in which MM patients had a DFS of only 10 months,23 but significantly shorter than the DFS of 16-68 months as seen MM patients in studies from developed countries.19 Similarly, DFS seen in SCC patients in our study was shorter when compared to that in the west (5.5 months vs 8 months).24
There are some other minor factors that may have affected outcomes in our patients. MM is more common in males when compared to females (approx. 55% vs 45%).25 However, it is much more common in females in the age bracket around 45 years25 which was the median age of MM patients in our study. But there were only 37.5% females with MM in our study. This reverse sex ratio may have had some bearing on the prognosis of MM patients in our study as in MM patients with nonmetastatic disease, females tend to have a better prognosis than males.25 However, this effect of sex on prognosis is not seen in SCC26 and is not clear for other malignancies. Duration of symptoms before surgery and type of reconstruction has no effect on prognosis in skin cancers26,27 although the longer duration of symptoms may suggest a slowly progressing disease, especially in SCC.26 Age has little impact on outcomes of SCC.26,28 However, it is generally accepted that younger patients with MM have a better prognosis when compared to older patients with MM.29 Our results were in contradiction, though, as even with a median age of 45.5 years in MM patients in our study (20 years less than the average age of presentation of MM patients in the USA),30 the prognosis of MM patients in our study was still worse. This paradox may be because of newly available systemic therapies, something that our patients may be largely devoid of and in the west, are more likely to be prescribed to younger patients, who are also more likely to complete such treatments when compared to the older population as they are more tolerant to newer systemic therapies.31 Location of the tumor may have also had a role. SCC arising in a scar is a poor prognostic marker32 and was present in 80% of our patients. On the contrary, MM arising in the lower limb, which was seen in 75% of MM patients in our study, should imply a better prognosis.33 However, this effect may have been nullified by the higher number of acral lentiginous subtype which is notorious for poor prognosis34(Figs 12 to 3).
Another reason for the poorer prognosis of skin malignancy patients in India may be inadequate adjuvant treatment. Even though we did not collect data on adjuvant treatment, many of the newer recommended adjuvant therapies like dabrafenib, trametinib, pembrolizumab, ipilimumab etc.,13 are not offered to patients in India with MM who have a high risk of relapse, either because of prohibitively high cost or non-availability at some centers. As for systemic therapies, there may be a gap in the delivery of adjuvant radiotherapy in patients with MM, SCC, DMFSP and MCC as well. Treatment in a tertiary care cancer center in which the surgical, medical and radiation oncologists can sit together in a tumor board meeting to decide upon the best approach for the patient may be an ideal setting for the treatment for these malignancies (Figs 4567 to 8).
Patients who received primary treatment which was not in accordance with the standard treatment guidelines did not have any significant impact on DFS. However, it did lead to an increase in morbidity in 40% of such patients.
Although there are certain limitations to our study like a small sample size with a few patients in each group because of which we could not compare the groups, a short follow up period and a referral bias as we are practicing in a tertiary care referral center, there are certain problems that have been highlighted by this study. We noticed that the median duration of symptoms in our study was 18 months. While most of the patients with MM had pigmentation, they waited for the disease to cause more significant symptoms like pain and ulceration and presented to us when it started to affect their activities of daily living, an effect that was seen in some previous studies as well.35 Similarly, most of the patients with SCC, despite the presence of an ulcer, presented only when they developed associated pain and patients with DMFSP and MCC presented when the lump increased to a significant size. Another problem we noted in our study was with the preoperative biopsies. Sixty percent of patients in our study with SCC and 12.5% with MM didn’t have a diagnosis of malignancy in the first biopsy that was performed elsewhere which may have led to a delay in presentation. Sometimes even many repeat punch or wedge biopsies may also not provide the desired information. In such situations, if the clinical suspicion is high, biopsies may be reviewed by an experienced dermato-pathologist. Even then, if the biopsy remains inconclusive and the clinical suspicion remains high, the clinician should perform an excision biopsy in accordance with the recommended guidelines for the suspected malignancy to eliminate any chance of unknowingly sitting on cancer.
The experience from Australia suggests that awareness programs about sun damage and early symptoms of skin cancers have not only increased the rates of early detection of skin cancers but also have given financial gain worth 2.6 times the money spent on such programs.36 Even though it may be a long time before we are able to emulate it in India, simple educational materials like posters, pamphlets etc., in dermatology and GP clinics and their websites stressing on skin health and self-examination can be a first step in that direction and may go a long way in helping patients by making them seek medical help earlier and thereby reducing morbidity and mortality related to skin cancers.
Melanoma and SCC have significantly worse outcomes in Indian patients when compared to western countries. Awareness programs for early diagnosis, a high index of suspicion and early referral to a center experienced in handling these malignancies are essential for improving outcomes.
Siddhant Khare https://orcid.org/0000-0001-9142-1115
2. GLOBOCAN 2018 Australia [Internet]. Gco.iarc.fr. 2020 [cited 17 May 2020]. Available from: https://gco.iarc.fr/today/data/factsheets/populations/36-australia-fact-sheets.pdf
4. GLOBOCAN 2018 USA [Internet]. Gco.iarc.fr. 2020 [cited 17 May 2020]. Available from: https://gco.iarc.fr/today/data/factsheets/populations/840-united-states-of-america-fact-sheets.pdf
5. GLOBOCAN 2018 India [Internet]. Gco.iarc.fr. 2020 [cited 17 May 2020]. Available from: https://gco.iarc.fr/today/data/factsheets/populations/356-india-fact-sheets.pdf
7. Ruiz R, Morante Z, Mantilla R, et al. Primary cutaneous T-cell lymphoma: experience from the Peruvian national cancer institute. An Bras Dermatol 2017;92(5):649–654. DOI: 10.1590/abd1806-4841.20176825
9. Cao J, Wang J, He C, et al. Angiosarcoma: a review of diagnosis and current treatment. Am J Cancer Res 2019;9(11):2303-2313
10. Deo SV, Hazarika S, Shukla NK, et al. Surgical management of skin cancers: experience from a regional cancer centre in North India. Indian J Cancer 2005;42(3):145–150. DOI: 10.4103/0019-509x.17059
11. Nair MK, Varghese C, Mahadevan S, et al. Cutaneous malignant melanoma- clinical epidemiology and survival. J Indian Med Assoc 1998;96:19–20
12. Vijaykumar DK, Kannan RR, Chaturvedi HK. Plantar acral melanoma-an experience from a regional cancer centre, India. Indian J Cancer 1996;33(3):122–129.
13. [Internet]. Nccn.org. 2020 [cited 15 May 2020]. Available from: https://www.nccn.org/professionals/physician_gls/pdf/cutaneous_melanoma.pdf
14. [Internet]. Nccn.org. 2020 [cited 15 May 2020]. Available from: https://www.nccn.org/professionals/physician_gls/pdf/squamous.pdf
15. [Internet]. Nccn.org. 2020 [cited 15 May 2020]. Available from: https://www.nccn.org/professionals/physician_gls/pdf/nmsc.pdf
16. [Internet]. Nccn.org. 2020 [cited 15 May 2020]. Available from: https://www.nccn.org/professionals/physician_gls/pdf/mcc.pdf
17. [Internet]. Nccn.org. 2020 [cited 15 May 2020]. Available from: https://www.nccn.org/professionals/physician_gls/PDF/dfsp.pdf
18. National Cancer Registration and Analysis Service. Routes to diagnosis of cancer by stage 2012–2013 workbook. London: NCRAS; 2016.
19. Spillane AJ, Pasquali S, Haydu LE, et al. Patterns of recurrence and survival after lymphadenectomy in melanoma patients: clarifying the effects of timing of surgery and lymph node tumor burden. Ann Surg Oncol 2014;21(1):292–299. DOI: 10.1245/s10434-013-3253-6
22. Meyer-Pannwitt U, Kummerfeldt K, Boubaris P, et al. Merkel cell carcinoma. Langenbecks Archiv für Chirurgie 1997;382(6):349.
24. Veness MJ, Morgan GJ, Palme CE, et al. Surgery and adjuvant radiotherapy in patients with cutaneous head and neck squamous cell carcinoma metastatic to lymph nodes: combined treatment should be considered best practice. Laryngoscope 2005;115(5):870–875. DOI: 10.1097/01.MLG.0000158349.64337.ED
26. Endo Y, Tanioka M, Miyachi Y. Prognostic factors in cutaneous squamous cell carcinoma: is patient delay in hospital visit a predictor of survival? ISRN Dermatol 2011;2011:285289. DOI: 10.5402/2011/285289
29. Cavanaugh-Hussey M, Mu E, Kang S, et al. Older age is associated with a higher incidence of melanoma death but a lower incidence of sentinel lymph node metastasis in the SEER databases (2003–2011). Ann Surg Oncol 2015;22(7):2120–2126. DOI: 10.1245/s10434-015-4538-8
30. Melanoma Skin Cancer Statistics [Internet]. Cancer.org. 2020 [cited 25 May 2020]. Available from: https://www.cancer.org/cancer/melanoma-skin-cancer/about/key-statistics.html
33. Garbe C, Büttner P, Bertz J, et al. Primary cutaneous melanoma. Prognostic classification of anatomic location. Cancer 1995;75(10):2492–2498. DOI: 10.1002/1097-0142(19950515)75:10<2492::aid-cncr2820751015>3.0.co;2-w
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