Gynaecological Oncology in India: Past, Present and Future

Abstract

Gynaecological cancers contribute to a substantial portion of the global cancer burden. Traditionally, these cancers have been treated by generalists, including gynaecologists and surgeons. However, owing to increasing sophistication and challenges in their management, a new sub-speciality of Gynaecologic Oncology, dedicated to these women’s comprehensive care, has emerged in recent times. The emergence and evolution of this sub-speciality will facilitate a holistic approach to treating women suffering from gynaecological cancers, including tailored surgical techniques, fertility preservation, precision medicine, hormone modulators, targeted therapy and immunotherapy, which can be achieved within the framework of multidisciplinary management. Hence, we decided to write this synopsis to shed light on the evolution of this discipline in India and offer current and future perspectives.

Raison d’être of Gynaecological Oncology

The Indian subcontinent had 678,383 new cancer cases in women per GLOBOCAN 2020 data. Almost 180,000 (25%) of these cases were gynaecological cancers [1]. The first point of healthcare contact for many women is their family physician, general practitioner or gynaecologist. Traditionally, gynaecological cancers have been treated by generalists (gynaecologists or surgeons) in most countries. However, owing to increasing sophistication and challenges in their management, a new sub-speciality dedicated to the comprehensive care of these women — ‘Gynaecologic Oncology’ — has recently emerged. There is now good evidence that management of gynaecological cancers by physicians specialised in gynaecologic oncology, working in dedicated multidisciplinary settings, results in better outcomes than management by less specialised physicians [2–4]. It is estimated that about one-fifth of women with gynaecological cancers are diagnosed in the reproductive age group [5]. A holistic approach to their management, including tailored surgical techniques, fertility preservation, hormone modulators, targeted therapy and immunotherapy, can be achieved within the framework of multidisciplinary gynaecologic oncology. This sub-speciality started developing in some Western countries in the early 1970s [6] and has since expanded in countries such as India, which contribute a major bulk to the global cancer burden.

Path Down the Memory Lane

The first radiotherapy unit in India was started in Calcutta Medical College Hospital in 1910 by the Countess of Minto [7]. In 1941, a major impetus to radiation oncology was given by Dr Ramaiah Naidu, a former associate of Marie Curie, who established the first radon plant of India at the Tata Memorial Hospital (TMH) [8]. The use of brachytherapy in India, which forms an integral part of modern cervical cancer management, dates back to the 1920s with radium as the source [8]. However, it was only after another six to seven decades that the current standard of remote after-loading brachytherapy units was introduced in India [9].

The surgical aspects of cancer treatment have been mentioned in the ancient scriptures by the great sages — Charaka and Sushrutha — in their respective treatises (‘Samhitas’) [10, 11]. Radical hysterectomies and cytoreductive surgeries are the foundation of gynaecological cancer treatment. Most of these techniques were discovered and refined in Western countries, especially during the tumultuous times of colonial expansion and world wars. Despite being disadvantaged during those times, there have been significant contributions from surgeons of Indian origin, such as Professor Subodh Mitra. He added extraperitoneal lymphadenectomy to the famous Schauta’s technique of radical vaginal hysterectomy [12].

Modern chemotherapy evolved to the present-day status from its inception in the days of the Second World War. Countless international scientists have contributed to this field. An often forgotten name is that of Dr Yellapragada Subbarao. He was an Indian-origin American researcher who discovered the anti-folate agents aminopterin and methotrexate, which are used to treat many cancers including gestational trophoblastic neoplasia (GTN). He also discovered adenosine triphosphate (ATP) as the cellular energy store [13].

Indian Contribution to Evidence and Literature in Gynaecological Oncology

In recent times, Indian studies have contributed to defining gynaecological cancer practice in various fields like preventive medicine, surgery, systemic therapy and radiotherapy. A brief review published a few years ago summarised the Indian contribution to gynaecological cancers [14]. We briefly highlight some important studies below.

A cluster randomised controlled trial conducted by investigators at Tata Memorial Centre, Mumbai, in 150,000 women showed that screening for cervix cancer with visual inspection with acetic acid (VIA) showed a statistically significant 32% reduction in cervical cancer mortality in the screened group [15]. Subsequently, VIA-based screening has been adopted for implementation at the primary and secondary healthcare levels throughout India. A previous study of VIA in Tamil Nadu also showed VIA to be an effective population-level cervical cancer screening method [16]. Another study in rural Maharashtra suggested that human papillomavirus (HPV)-based screening is also an effective screening strategy for the Indian population [17]. In the domain of primary prevention, analyses from India have suggested that a single dose of HPV vaccine may have similar immunogenicity to two- or three-dose schedules [18]. However, because of decreasing cervical cancer incidence in almost all regions of India [19], others have questioned the need for population-level HPV vaccination [20].

In terms of cervical cancer treatment, important studies from India have focused on the management of locally advanced disease and refining adjuvant treatment in this disease. Two landmark studies from Tata Memorial Centre showed significantly higher disease-free and overall survival with cisplatin-based concomitant chemo-radiotherapy compared to radiotherapy in patients with stage IIIB disease [21], and significantly higher disease-free survival with concomitant chemo-radiotherapy compared to neoadjuvant chemotherapy followed by surgery in patients with stage IB2 to IIB disease [22], respectively. More recently, the PARCER trial, from Tata Memorial Centre, showed that intensity-modulated image-guided post-operative adjuvant radiotherapy (IMRT) resulted in significantly lower toxicity than conventional 3D conformal radiotherapy [23], with the implication that IMRT should be the standard of care in this setting. Another study from the same centre explored the prognostic value of persistent HPV infection in patients diagnosed with cervical cancer [24]. Notably, Indian gynaecologic oncologists led the effort to develop the 2018 FIGO staging system for cervical cancer [25, 26]. The status of cervical cancer research in India has been well summarised in a recent review [27]. There are well-developed contextual guidelines for managing cervical cancer in India [28].

There have been fewer contributions from India in gynaecological malignancies other than cervical cancer. Indian gynaecological oncologists have reported good outcomes of neoadjuvant chemotherapy in ovarian cancer [29], a high incidence (~ 20%) of germline pathogenic BRCA 1 or BRCA 2 among unselected ovarian cancer patients [30] and the potential utility of poly-ADP ribose polymerase (PARP) inhibitors in patients with platinum-resistant ovarian cancer [31]. Indian researchers recently published the first and only individual patient data meta-analysis of PARP inhibitors in the first-line treatment of ovarian cancer, showing that this drug class improves disease-free survival in patients with BRCA mutations (germline or somatic) and homologous recombination deficient tumours, but not in those with homologous recombination proficient tumours [32]. At the population level, the Mumbai Cancer Registry has reported that the incidence of ovarian cancer is gradually increasing in urban regions [33]. In 2017, the Indian Society of Peritoneal Surface Malignancies was started by a multidisciplinary group of oncologists who also initiated the Indian HIPEC (Hyperthermic Intraperitoneal Chemotherapy) Registry. This Registry is facilitating the collection of prospective data and creating an evidence base for the use of this procedure [34]. An analysis of 1470 ovarian cancer patients who underwent cytoreductive surgery with HIPEC, presented in the ASCO 2022 Annual Meeting, suggested a possible improvement in progression-free survival (PFS) in patients with primary and recurrent ovarian cancer [35]. There is an ongoing randomised controlled trial comparing HIPEC with standard treatment in first-line ovarian cancer in Tata Memorial Centre, whose results are expected in 4–5 years [36].

Evolution of Gynaecological Oncology Training

The American College of Obstetrics and Gynecology defines a sub-specialist in gynaecological cancers as an obstetrics and gynaecology physician who provides comprehensive management to gynaecologic cancer patients in a multidisciplinary institutional setting where all modalities of cancer therapy are available [37]. The United States National Cancer Institute (NCI) defines a gynaecologic oncologist as a physician who has received special training in diagnosing and treating cancers of the female reproductive organs [38].

The concept of surgeons dedicated to oncology was not well accepted in Western countries in the past. Complex oncological surgical procedures were performed by experienced surgeons, who were traditionally not focused on cancer care. There was deficient acknowledgement that clinical decision-making is better accomplished with a sound knowledge of the biological basis of the disease process and organ-based anatomy. Eventually, the speciality of gynaecological oncology was one of the first dedicated surgical specialities to be incorporated as a part of cancer centres in Western countries [39].

However, like all cancers, management of gynaecological malignancies has become increasingly complex, requiring multidisciplinary inputs, which is challenging to deliver in low- and middle-income countries. Therefore, training individuals who could become dedicated experts in gynaecological cancers is a pressing need. Many gynaecologists interested in cancer management started dedicated work in oncology. The concept of gynaecological oncology as a sub-speciality in India has its beginnings in the early 1980s when surgical and radiotherapy departments, providing short-term training, were set up in the regional cancer centres under the auspices of the National Cancer Control Programme. Gynaecologic Oncology received a major boost with the formation of the Association of Gynaecologic Oncologists of India (AGOI) in 1991. Since its inception, AGOI has worked towards early detection and appropriate management of gynaecological malignancies [40]. Formal fellowship programmes in gynaecologic oncology were started in a few tertiary cancer centres, which were later recognised by the respective universities and AGOI. The Tata Memorial Centre, Mumbai, started the first Medical Council of India approved gynaecological oncology M.Ch course in India in 2011. There has been a substantial increase in the number of gynaecologic oncology training programmes in the past decade, with ten centres now offering M.Ch courses and seven centres the DrNB course. Admissions to these courses are made through the super-speciality national entrance and eligibility test (NEET-SS) [41].

Future Perspectives

A multidimensional approach of strengthening preventive services, building a nationwide network of well-trained gynaecologic oncologists and setting up a referral system to ensure appropriate utilisation of services is necessary to deliver good quality care to patients and conduct locally relevant research activities.

In this context, the key to decreasing morbidity and mortality of already diagnosed malignancies is to train gynaecologic oncologists, other oncologists and medical staff in centres with adequate infrastructure and caseload. A well-designed curriculum and skills training are essential components of a good gynaecologic oncology course. Although there are a few well-structured training programmes in India now, exposure to modern practices in gynaecological oncology surgery, chemotherapy and radiation oncology is still insufficient in most other centres. Political, administrative and academic initiatives are required to train physicians and other paramedical staff who can serve at different levels in the community. In this context, the complex nature of gynaecological malignancies requires a multidisciplinary approach with the integration of trained personnel from physiotherapy, occupational therapy, psycho-oncology, palliative care and other relevant disciplines in a centralised care pathway.

Conclusion

Gynaecological oncology is now a well-established oncological sub-speciality in India. However, it has miles to go before it can deliver the service, education and research in gynaecological cancers that our society deserves.

Declarations

Conflict of Interest

The authors declare no competing interests.