Oncology: Treating the unmet needs
Dr Asma Mohd Yousuf
Cancer management involves a combination of many therapies. Chances of infertility are high following the aggressive cancer treatment. However, oncofertility offers hope to all patients who have fears of conceiving post cancer treatment.
The prevalence of cancer in India is rising in quantum leaps. Today, oncology OPDs of every hospital in India are overcrowded. Increased awareness among the masses along with better diagnostic procedures are some of the reasons why more and more people are diagnosed with cancer.
“The current prevalence is approximately 30 lakh cases in our country, and in 2010 there were 10 lakh new cases. The estimated load in our country could exceed that of cardiac-related diseases by 2015. The male to female ratio of cancer in India is almost equal. The common cancers found in Indian men are cancers of the mouth, tongue larynx, lung and upper digestive tract, which are all tobacco-related. In women breast cancers and cervical cancers had the maximum incidence, with breast cancer more prevalent in urban areas and cervix cancer more in the rural areas,” points out Dr Dhairyasheel Savant, Consultant Surgical Oncologist, Reconstructive & Microvascular Surgeon at SL Raheja Hospital (a Fortis associate), Mumbai.
Cancer prevalence in India is estimated to be around 2.5 million with over 8,00,000 new cases and 5,50,000 deaths occurring each year, informs Dr Rashmi Yogish, Obstretician and Gynaecologist, The Lady Hospitals, Bengaluru.
She further adds, “Overall cancer in childhood is more common among males than females. The reported incidence of childhood cancer in India in males (39-150 per million children per year) is higher than in females (23-97 per million children per year), except in North East India, and this gives a male to female ratio that is much higher than what is seen in the developed world. It remains to be determined if this is a true difference or a registration artifact.”
Further Dr Niti Raizada Narang, Consultant Medical Oncologist, Vital Diagnostic Clinic, Bengaluru, adds, “Over 70 per cent of the cases report for diagnostic and treatment services in advanced stages of the disease, resulting in poor survival and high mortality rates. The disease is associated with a lot of fear and stigma in the country. But what is worth emphasising is that now with improving treatment modalities, ‘cancer survivorship’ has increased and so issues like fertility preservation are being brought to the forefront.”
Imaging diagnostics: An oncological risk factor?
The presence of cancer can be suspected on the basis of symptoms or findings on radiology. Definitive diagnosis of cancer, however, requires microscopic examination of a biopsy specimen. Dr Anita Balakrishna, Consultant Gynaecologist, Motherhood, Bengaluru, says, “Repeated exposure to radiations poses health hazards as these electromagnetic ionising radiation (like X rays) can remove the electrons from the molecules producing free radicals. This is responsible for molecular damage like mutations and chromosomal aberrations causing abnormal reproductive capacity.”
Medical use of ionising radiation is a growing source of radiation-induced cancers. Ionising radiation may be used to treat other cancers, but this may, in some cases, induce a second form of cancer. It is also used in some kinds of medical imaging.
Dr Rakesh Badhe, Onco Surgeon, Kohinoor Hospital, Mumbai, mentions a report that estimates approximately 29,000 future cancers could be related to the approximately 70 million CT scans performed in the US in 2007. He further adds, “It is estimated that 0.4 per cent of current cancers in the US are due to CTs performed in the past and this may increase to as high as 1.5-2 per cent considering the 2007 rates of CT usage.”
Treatment: A hindrance?
Surgery, radiotherapy and chemotherapy are the main stay of treatment in cancer patients. However, all the three modalities can affect the reproductive health of both the males and females. Radical surgery done for most female gynaecological cancers involves the removal of both ovaries along with the uterus. Radiotherapy uses high-energy radiations to kill cancer cells, which can also kill gonadal cells apart from causing fibrosis, stenosis, scarring and permanent sterility. Chemotherapy kills the fast multiplying cells targeted at the cancer cells. These cytotoxic drugs affect other tissues as well and can cause immediate infertility or premature loss of reproductive function.
Dr Savant explains, “In the female, the ovary is particularly sensitive to the adverse effects of chemotherapy and radiation due to its finite number of unrenewable germ cells. Alkylating agents and pelvic irradiation pose the greatest threat to ovarian function. In addition, the uterine effects of pelvic irradiation may contribute to infertility and increase the risk of pregnancy loss. Premature ovarian failure not only causes infertility but can lead to long-term health problems such as osteoporosis, cardiovascular disease and sexual problems in women.” He further adds, “Cancer therapies also affect reproductive function in males. Both chemotherapy, particularly alkylating agents such as cisplatin, and testicular radiation pose a threat to future fertility. In addition, some surgical treatments for cancer can have an effect on transport of sperm and ejaculatory function, eg, surgery for rectal cancers. In both males and females, cranial irradiation can have a profound effect on pubertal development and long-term reproductive function.”
Many anticancer agents damage DNA and interfere with its replication and repair and with chromosome segregation in both animal and human cells, which can cause genetic diseases in the offspring. Agrees Dr Nitin Pai-Dhungat, Consultant Obstetrician and Gynaecologist, Bombay Hospital, Mumbai, “Chemotherapy acts on rapidly dividing cells. Different drugs act at different times in cell division. Therefore, there is a higher risk of genetic abnormalities after someone has received chemotherapy. However, it also depends on the dosage and the drugs used. Some drugs like the alkylating agents, cyclophosphamide and nitrogen mustard are particularly toxic to the testis and can cause permanent sterility.”
What is oncofertility?
The emergent discipline of oncofertility, an intersection between oncology and fertility, recognises that cancer patients and cancer survivors have legitimate concerns about their fertility. Common cancer treatments such as chemotherapy and radiation pose a great threat to reproductive functioning, and infertility is a very common side effect of cancer therapy. Oncofertility addresses these concerns, using both existing fertility preservation technologies and developing new techniques to accommodate the unique concerns of cancer patients.
Highlighting on this subject, Dr Badhe explains, “The Oncofertility Consortium is a multi-institutional project to assess the impact of cancer and its treatment on reproductive health. The term was coined in 2006 by Dr Teresa Woodruff, at the Feinberg School of Medicine (Northwestern University, Chicago). By aggressively applying new reproduction techniques it can help improve the fertility prospects of cancer patients.”
Discussing the methods available for preserving fertility in women, Dr Badhe informs, “The first method is cryopreservation that is generally done in pre-pubertal girls, where the ovarian tissue is taken and preserved in deep freeze. This can be later auto-transplanted. Stimulating the ovary to produce lots of eggs and preserving them in deep freeze to use later for conception is the second method applied in female patients.” He continues, “The third method is removing eggs, mixing them with sperm, creating an embryo and preserving it, and the fourth method includes using Gonadotropin-releasing hormone (GnRH) analogues, which is given before chemotherapy begins. This injection protects the ovaries from the effects of chemotherapy.”
Further informing on the fertility preservation methods used in male patients, Dr Balakrishna says, “In men, infertility may precede the disease itself. Further, chemotherapy or radiation therapy can cause decrease in the sperm count, motility, morphology and DNA integrity. Due to the advances in fertilisation and sperm banking technologies, all men, even those with extremely low sperm counts and motility, should be considered candidates for sperm cyropreservation. Sperm should be collected before initiation of cancer therapy; however, men with testicular cancer or Hodgkin’s lymphoma may have particularly poor sperm quality. Hormonal therapy has not been successful in preserving fertility or speeding the recovery of spermatogenesis.”
However, given the potential of cancer therapies to cause reproductive problems, it is important to monitor a patient’s reproductive function after cancer therapy. Avers Dr Savant, “Cancer survivors at risk for infertility should be counselled about pursuing pregnancy as soon as appropriate because the age-related decline in fertility may occur at an earlier age. In addition, cancer survivors experiencing delayed conception should be evaluated by a fertility specialist sooner than normally recommended (before 12 months of unprotected intercourse) given that such couples may have a shorter fertile window compared to couples without a history of cancer. Post-therapy options for having a family include fertility treatments including IVF, the use of donated gametes or embryos, or adoption.”
The discovery of new and more efficient anti-cancer drugs has increased the survival of the young cancer patients. The aggressive treatment has created new health problems, which were not anticipated at the time of diagnosis. Discussing the measures taken to preserve fertility in kids and teenagers, Dr Pai-Dhungat says, “Kids and teenagers who have not reached puberty most often do not need measures to preserve fertility. The reason chemotherapy or radiotherapy act more on cancer cells and less on normal cells is because they act at the level of cell division, so obviously those cells which are rapidly dividing are more prone to the action of chemotherapy/radiotherapy. In adults, the testis and the ovaries have some of the most rapidly dividing cells and the drugs have an adverse effect on them as well. However, in kids and teenagers who have not reached puberty, the testis and ovaries have not started function, ie, rapid cell division and hence they are much more resistant to the effects of chemo/radio therapy.”
Facilities in India
According to Dr Pai-Dhungat, “Sperm banking is readily available in India. Embryo freezing is also readily available. However, storage of ova (eggs) and the ovarian tissue is much more difficult. It is not a problem prevalent only in India but all over the world. However, things are looking up in this respect with the availability of blast freezing.”
Meanwhile, Dr Badhe adds, “The average cost of IVF cycle in the USA is around $7500 to 9000, whereas the discounted cost of IVF cycle in India is around $1500. The facilities are present in many private hospitals in various cities like Mumbai, Chennai, Delhi, Noida, Pune, Banglaru and many other parts of India. These facilities are at par with those in the developed world.”
However, Dr Narang feels, “Facilities like these are rapidly evolving in our country and most big cities have good facilities. But what is important here is that the oncologist needs to be cognisant of the patients’ needs and should be able to discuss fertility and fertility preservation options to their patients in the reproductive age group. ‘Timely intervention’ is probably the bottom line. It is vital to discuss these options before starting cancer-directed treatment so that whatever possible can be done at that juncture. Also, a subset of treated patient can regain ‘natural fertility’ some time later after treatment and so discussion with the oncologist and reproductive medicine specialist may be vital.”
Providing details on the legal issues involved, Dr Balakrishna says, “Fertility preservation counselling is to be offered to all patients who are under 45 years and also to anyone who expresses an interest regardless of the prognosis of the cancer. Women have the legal rights to decide if they want to parent a child. Future fertility options following cancer treatment must be considered in the patient’s best interest. The advantages of any fertility preservation must outweigh the disadvantages, both in short and long term. Every attempt is made such that the patient fully understands the risks and the benefits of her treatment plan. Any intervention must be evidence based as well as morally right. It should not give rise to unrealistic expectations nor have long-term adverse effects on the patients or the offspring. She further adds, “There is an increased risk of abnormalities with the use of Intracytoplasmic Sperm Injection (ICSI). There is also the probability of an increased risk of abortion and of genetic defects in offspring conceived soon after chemotherapy. Informed consent should be given voluntarily by the patient after discussing the complexity of the issues surrounding the fertility preservation. The consent should first be obtained for the collection and storage of the gametes. Later, consent is also obtained for the use of collected material for fertilisation or reimplantation. It is important to discuss with the patient and their family, of what could happen to the stored samples in the event of the death of the patient during the course of treatment. Some would seek to discard the samples whereas others may choose to donate for research purposes.”
What future beholds?
Recent diagnostic and therapeutic advances in oncology have led to greater survival rates in children and reproductive aged adults with malignancies. Clinicians must be aware of the reproductive consequences of cancer therapies in order to anticipate and address the needs of cancer survivors so that they can lead healthy, fulfilled lives.
Dr Savant says, “Cancer patients of all age groups and gender who choose to pursue fertility preservation in the face of a cancer diagnosis demonstrate faith and attribute value to their capacity to reproduce at a time when their physical bodies are at risk of not supporting their own lives. Modern science is offering a new option to cancer patients, an option that forces patients to think about creating a new life at a time when their own life is being questioned.” He further adds that understanding the biological, social and psychosocial roots of these parenting desires can hopefully help healthcare practitioners in best counselling their patients during the decision-making period and thereafter.
“A journey of 1000 miles begins with a first step. The first few steps have already been taken but we have a very long way to go. At best it can be summarised that the field is in its infancy and it will require a lot of effort on the part of oncology community, medical fraternity and civil society for the field of oncofertility to reach its logical ends,” concludes Dr Badhe.