Question 1

What are the preventive measures for PCOS?

Dr. Punyashree R M · Accepted Answer

PCOS is largely a lifestyle disease: if you correct the lifestyle, the hormones often come under control. Most of the time we do not put patients on hormonal pills upfront. We take time to explain what is causing the imbalance, even drawing diagrams of the ovary, so that they understand the importance of a healthy lifestyle, which means not only diet and exercise but also stress management and sleep. We give them 3 to 4 months to work on this. Around 60 to 70 percent of our patients come back at the end of 3 months with regular cycles. At the first visit we also check for other hormonal issues and for vitamin D and B12 deficiencies, and correct them in parallel. A good lifestyle is the best preventive measure.

Question 2

Is fertility-sparing treatment appropriate for ovarian cancer?

Dr. Punyashree R M · Accepted Answer

Fertility-sparing treatment is offered only if the woman desires fertility and the disease is early: confined to a single ovary, with no peritoneal deposits and no malignant cells in the ascites, especially stage IA. Even when disease appears confined to one ovary, we sometimes do a diagnostic laparoscopy to see whether the other ovary is involved, because imaging may not pick up surface deposits on it, and we biopsy those. The tumour type also matters: germ cell, sex cord-stromal or epithelial. Germ cell tumours are always managed with fertility-sparing surgery because they respond well to treatment; for other tumours we explain the possible complications if the disease is not completely staged, so the decision has to be tailor-made. We also always offer egg freezing (cryopreservation) until adjuvant therapy is complete, because chemotherapy can suppress the healthy ovary. We work with the infertility specialist and let the patient make an informed choice before fertility-sparing therapy.

Question 3

How is advanced-stage cervical cancer managed differently from early-stage disease?

Dr. Punyashree R M · Accepted Answer

Micro-invasive early-stage disease, stage IA1 and IA2, needs only surgery, a simple extrafascial hysterectomy or even a trachelectomy or a cone, usually without adjuvant therapy. For macroscopic disease, stage IB1, IB2 and IIA1, the size and type of the tumour decide whether surgery followed by radiation is needed, and a patient unfit for surgery is offered radiation therapy. Locally advanced disease, stage III and IV, is usually treated with chemotherapy and radiation: squamous cell carcinomas are radiosensitive, and chemotherapy is given as a radiosensitiser so that the response is better. Stage IVB disease with distant metastases needs systemic therapy. Even after this, if there is residual disease and the patient's performance status is good, we go back and remove it, by radical hysterectomy or anterior, posterior or total exenteration depending on where the tumour is and how big it is. So advanced cervical cancer is treated either with neoadjuvant chemotherapy, then surgery, then chemoradiation, or with direct chemoradiation, depending on the response, followed by an exenterative procedure if needed.

Question 4

Which technique do you recommend for locating the sentinel lymph node?

Dr. Punyashree R M · Accepted Answer

We do sentinel lymph node mapping in early-stage endometrial and cervical cancer. We use ICG (indocyanine green) dye, robotically or laparoscopically with a 4K system and the Firefly technique, injecting into the cervix at the 3 o'clock and 9 o'clock positions. Before injecting, we open the retroperitoneal spaces, identify the external iliac vein, open the obturator spaces and get everything ready; then we inject and, within 5 to 7 minutes, switch on Firefly to see which node glows, most often the obturator group. If you inject first and then dissect, any bleeding will stop you locating the node properly. The first node to glow is removed completely and sent to a good oncopathologist for frozen section and ultrastaging, so that micrometastases are not missed. If you are introducing the technique at your centre, do a pilot study of at least 25 cases each of endometrial and cervical cancer, with complete lymph node dissection, to confirm that you are picking up the sentinel node correctly and that your pathologist is reporting it correctly, before using it as the method of choice.

Question 5

What are the post-operative morbidities associated with radical hysterectomy with lymph node dissection?

Dr. Punyashree R M · Accepted Answer

We perform a nerve-sparing radical hysterectomy, for early-stage cervical cancer and for stage II endometrial cancer. The most common complication is urinary dysfunction, but only about one or two of every 100 patients we operate on have it, because we identify the hypogastric plexus and the inferior hypogastric nerve and try to preserve them. It is harder when the tumour infiltrates or is stuck to the nerve; those patients do have urinary issues, which we manage with bladder training, and they are mostly transient if the surgery is good and the nerves are spared. With lymph node dissection, apart from intraoperative vessel injury, the obturator nerve needs care while dissecting the obturator nodes; if it is damaged, it can be repaired with a 4-0 or 6-0 suture and the patient given physiotherapy. Lymphoedema of the legs, the counterpart of arm lymphoedema after axillary dissection, is something we have not seen so far after pelvic lymph node dissection. We give DVT prophylaxis and follow the ERAS (enhanced recovery after surgery) protocol: the patient is out of bed the same day, clear liquids start within 4 hours and a liquid diet within 6 hours. When these protocols are followed, morbidity is low, because the patient's physiology stays close to its pre-operative state.

Question 6

What is the current role of HPV testing versus Pap smear in cervical cancer screening?

Dr. Punyashree R M · Accepted Answer

A Pap smear can be started at 21 years, while HPV testing is done from 30 years. A Pap smear looks for abnormal cells, whereas HPV testing looks for HPV DNA. If the Pap smear is normal, HPV testing is not compulsory, but if it is abnormal, the next step is colposcopy. Co-testing is best, because it shows whether abnormal cells are present together with HPV. As a screening method either can be used. HPV DNA testing is done once in 5 years, so it is more acceptable to patients, and it is more sensitive than cytology, whether conventional or liquid-based, but it is more expensive than a Pap smear. Both are good; the choice depends on the centre and is discussed with the patient.

Question 7

What is the emerging role of imaging versus histopathology in staging endometrial cancer?

Dr. Punyashree R M · Accepted Answer

Every suspected endometrial cancer needs histopathology. The gold standard is a hysteroscopy-guided biopsy, but an endometrial pipelle biopsy in the OPD or a D&C is also acceptable. Histopathology gives the type and grade of the tumour, and that decides the imaging. For a grade 1 endometrioid adenocarcinoma, a favourable type, that appears confined to the uterus on ultrasound, an MRI of the abdomen and pelvis with contrast and diffusion-weighted images is enough, and it shows whether the tumour invades the myometrium. For a high-grade serous or clear cell carcinoma, the unfavourable type 2 cancers that spread early beyond the uterus, a full-body PET-CT is the better imaging modality.

Question 8

Full-body PET-CT is not widely available in Ethiopia and most sub-Saharan African countries. Where MRI and CT are available, what are the alternatives?

Dr. Punyashree R M · Accepted Answer

For a suspected early-stage disease, an MRI with contrast and diffusion-weighted images gives the best idea of the size of the disease, any myometrial invasion and whether the serosa is involved. For an unfavourable type 2 cancer, do the MRI of the abdomen and pelvis and add a CT of the chest to look for disease outside the abdomen. If PET-CT is not available, a screening CT of the thorax should be good.

Question 9

If the HPV vaccine can prevent many cervical cancers, why has it not been widely adopted?

Dr. Punyashree R M · Accepted Answer

The HPV vaccine was licensed in 2006 and introduced to the public in 2007. The Australian government incorporated it into its national immunisation programme for schoolgirls, and in 2013 included boys as well, since they spread the virus as adults; Australia is now on course to eliminate cervical cancer, which shows how effective the vaccine is. India developed its own indigenous quadrivalent vaccine two years ago, available at a much lower price than the imported vaccine, and its efficacy is being studied while awareness is built. The challenge in countries like ours is scale: the population is huge, so the resources must be huge, and awareness has to be created against stigma, since many people will not even sit through a cancer awareness talk. Government, society and NGOs all have to pitch in. Many doctors and NGOs are working to get the Indian-made vaccine into the national immunisation schedule so that all girls and boys are vaccinated, and as awareness grows we see more people coming to the OPD just for the vaccine.

Question 10

Could HPV vaccination programmes be run in our countries, and what would the vaccine cost per dose and per person?

Dr. Punyashree R M · Accepted Answer

Indian vaccines are currently given only in India. About 60 percent of the vaccines manufactured go to the government programme for vaccinating girls, prioritising underprivileged populations who would not otherwise come to a healthcare facility, and only around 40 percent are available to private hospitals, so I am not sure supply to another country will happen for now. The market price of the Indian vaccine is around 1,800 to 2,000 rupees, about half the price of the quadrivalent Gardasil at around 4,000 rupees, while Gardasil 9 costs around 10,000 rupees; it is free for those in the target age group. The Indian vaccine was introduced two years ago, so another decade may be needed for exact efficacy figures, but because its virus-like particles are similar to those of existing vaccines, it is expected to be effective. A national programme is ultimately a decision for the government.

Question 11

Is one ampoule for one person, and how many doses does a child need?

Dr. Punyashree R M · Accepted Answer

Yes, one ampoule of 0.5 ml is for one person. The best age is 9 to 14 years; in that age group, two doses six months apart are enough, with no booster required, and protection has so far proved long-lasting. Between 15 and 45 years, three doses are needed, at 0, 2 and 6 months.

Question 12

Given the growing role of molecular profiling, how do you prioritise patients for targeted therapies where access is limited?

Dr. Punyashree R M · Accepted Answer

All endometrial cancer patients should now undergo molecular profiling, which places them in four categories. If the tumour is POLE-mutated, the prognosis is good even when it is high grade, so I would not add multiple treatment modalities: in stage I to II disease, surgery with radiation would probably do. If it is p53-abnormal, I make sure the patient receives all six doses of chemotherapy on time, with adjuvant radiation if needed, to reduce recurrence and improve overall survival. Hormone therapy depends on ER and PR status and is not commonly given in endometrial cancer. Targeted therapies are still being studied and depend on the tumour type; not every patient gets them, and we use them in recurrent settings or unusual varieties, mostly as maintenance. Where access is limited, the conventional therapies are good enough, provided there is the facility to keep monitoring the patient, pick up a recurrence early and treat it. Where facilities exist, maintenance targeted therapy is a good choice for a selected population, not for everyone.

Live Discussion with Dr. Punyashree R M