|Year : 2021 | Volume
| Issue : 4 | Page : 728-730
Melanoma: Gaps in knowledge and treatment
Anand Raja, Chandra Kumar Krishnan
Department of Surgical Oncology, Cancer Institute (WIA), Chennai, Tamil Nadu, India
|Date of Submission||02-Dec-2021|
|Date of Decision||07-Dec-2021|
|Date of Acceptance||08-Dec-2021|
|Date of Web Publication||29-Dec-2021|
Department of Surgical Oncology, Cancer Institute (WIA), 38, Sardar Patel Road, Chennai - 600 036, Tamil Nadu
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Raja A, Krishnan CK. Melanoma: Gaps in knowledge and treatment. Cancer Res Stat Treat 2021;4:728-30
Melanomas are rare malignancies. In India, they account for 0.5% of all cancers in men and 0.3% of all cancers in women, with a corresponding lifetime cumulative risk of 0.043% and 0.028%, respectively. The crude incidence rate is 0.4 and 0.3 per 100,000 men and women, respectively. Melanomas comprise 20.32% and 21.21% of all skin cancers among men and women, respectively. The incidence of melanoma varies widely in India. The age-adjusted incidence rate (AAR) of melanoma of the skin is reported to be the highest in the northern region of the country, being 1.62 among men and 1.21 among women; it is least in the western region of the country, with an AAR of 0.21 for men and 0.16 for women. Data from India regarding the differential distribution of cutaneous and mucosal melanomas are scarce, but the incidence has been reported to be 93.4% for cutaneous and 6.6% for mucosal melanomas.
As in any rare disease, high-quality data with regard to epidemiology, location, mutational analysis, stage distribution, and patterns of care are lacking from our country. Potential confounding factors include limited access to health care, the chance of mucosal melanomas remaining undetected, and poor socio-economic status. Retrospective studies from major institutions exist with regard to the type, location, stage, and outcomes of melanoma,, but they are prone to bias either because the patients have undergone prior surgical interventions or the data are obtained from an isolated department.
The basis for a paradigm shift in the treatment of melanomas was the pioneering immunotherapy research by Allison and Honjo on checkpoint inhibitors and programmed cell death protein 1 (PD1), for which they received the Nobel Prize in 2018. Treatment of melanomas entered an exciting territory after the translation of their basic research led to the development of multiple therapeutic options.
The current standard as adjuvant therapy in completely resected stage IIIB/IIIC melanoma is anti-PD1 therapy and BRAF-MEK inhibition. Neoadjuvant therapy is not yet a standard but is an area of active research. Metastatic melanoma was thought of as having a dismal prognosis. Mortality for advanced melanoma in the western world has continued to decline, mainly over the past 10 years. The treatment has radically changed with the introduction of combination therapies, ipilimumab and nivolumab, with a 53% response rate; combined BRAF-MEK inhibition has shown response rates of 60%, with complete response rates of up to 18%. Mutations in KIT can be found in mucosal and acral melanomas, which may confer responsiveness to imatinib. A major limitation to the use of these therapies is the development of resistance. Most patients in practice end up receiving both targeted therapy and immunotherapy.
This is an exciting time for melanoma research. The landscape is brimming with new and evolving therapeutic options, including adoptive cell therapy, chimeric antigen receptor T-cell therapy, T-cell receptor therapy, and therapeutic vaccines.
Most patients in our country cannot afford testing for BRAF, RAS, NF1, and KIT mutations. Even when testing is performed, the cost is a deterrent for treatment. Patients simply cannot afford immunotherapy or targeted therapy., Immunotherapy and targeted therapy are not available even in large tertiary care hospitals funded by the government. Most patients end up getting dacarbazine because it is freely available. The high cost of treatment has resulted in dismal survival of 0% at 2 years for metastatic melanoma at our institution (unpublished data). This juxtaposed with the 3-year survival of about 26.4% for metastatic melanoma from the Surveillance, Epidemiology, and End Results program gives us a measure of the magnitude of gap in the delivery of health care in our country.,
Another problem that immensely impacts cancer outcomes is patient dropout. This problem is acute in melanoma and rises alarmingly after the diagnosis of metastasis.
In the current issue of Cancer Research, Statistics, and Treatment, Shishak et al. present a retrospective audit for unresectable/metastatic melanoma on patterns of care and evaluate oncological outcomes from the Medical Oncology Department of the All India Institute of Medical Sciences, a tertiary referral hospital in Delhi, India. This paper beautifully brings out the challenges we need to surmount. The proportion of patients undergoing BRAF testing was only 4.3%. Similarly, low rates of BRAF testing (6.98%) were reported by Bajpai et al. on patterns of care from a major cancer referral center in India conducted on 433 patients with metastatic melanoma. No patient could afford combined BRAF-MEK testing.
In Shishak et al.'s study, only 53.8% received any therapy, <50% were evaluable for response, and only 17.2% patients received immunotherapy. This is somewhat consistent with the results reported by Bajpai et al., where 25.4% of all patients were offered best supportive care and 13.6% defaulted on treatment. An important aspect of the current study is the wide variation in patients not evaluable and evaluable for response assessment between the chemotherapy and immunotherapy groups. The ratio was 28:22 for the chemotherapy group and 1:16 for the immunotherapy groups. Various reasons could account for this, including the burden of metastasis, performance status, and socio-economic status among others. It could be argued that with wider availability and use of the advanced therapeutic options, the delivery of health care, follow-up, and outcomes can be improved. In Shishak et al.'s study, the median progression-free survival and overall survival (OS) were 2 and 7 months, respectively. An extension to this baseline survival statistics in our country was provided by Bajpai et al.'s study where the median OS was 3.9 months for best supportive care alone versus 12 months with any systemic treatment (P < 0.0001). This paper helps to establish some baseline values for a real-world experience in our country.
The path to improved outcomes in our country is not easy. There are several ways to improve the outcomes, including increased testing for mutation, along with improving access and penetration and reducing the treatment cost; modifying immunotherapy regimens by reducing their duration and/or dose or using intermittent therapy; providing patient support programs; and improving the availability of generics. Melanomas are rare cancers, and in the absence of robust data, the above strategies would be difficult to implement in an evidence-based world. This underscores the need for an India-specific melanoma study group/national registry and academia–industry collaborations to optimize the outcomes.
Melanoma is a highly immunogenic tumor, and immunotherapy is the standard of care. But when immunotherapy is not feasible, any systemic therapy is better than no treatment. Evaluating the efficacy of non-immunotherapy-based systemic therapy regimens and variations in dosage/schedule of drugs to optimize the cost-benefit ratio may require collaborative studies.
The lacunae are many. The challenges seem insurmountable. Collaborative studies are the need of the hour; this is something that is often said but seldom practiced. The only thing left for us to do is to get together and fill in the gaps!
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