A New Path to Ovarian Cancer Prevention: The SOROCk Study is now open to High-Risk (BRCA1+) Women in BC

Research suggests that the majority of ovarian cancers in women may originate in the fallopian tubes rather than the ovaries. Reflecting these findings, an exciting new approach to risk-reducing surgery is now available to some high-risk women in British Columbia through a UBC branch of a multi-national clinical trial called the SOROCk (Salpingectomy versus Salpingo-oophorectomy to Reduce risk of Ovarian Cancer) study, led locally by Dr. Janice Kwon.

Background

BRCA1 and BRCA2 carriers face a 17%-44% lifetime risk of ovarian cancer and are traditionally offered the choice of removing their ovaries and fallopian tubes with a surgery called prophylactic salpingo-oophorectomy (rrSO) (Kuchenbaecker et al., 2017). This risk-reducing surgery can be successful in decreasing ovarian cancer incidence by up to 96%, but it is not without drawbacks (Boerner et al., 2021). As a consequence of removing the ovaries, which produce estrogen, women (if they were still pre-menopausal) are put into what is commonly called “surgical menopause.”

Given that the surgeries are on average performed 10-15 years before natural menopause, women must navigate a variety of health risks from early menopause including increased osteoporosis risk to sexual health challenges (Kaunitz et al., 2021). This premature start of menopause is thought to have both short-term and long-term impacts on the health and quality of life of women.

Studies such as PROTECTOR in the UK and SOROCk in the United States are investigating a two-step approach where one surgery is done to remove only the fallopian tubes, and a second is done five to ten years later to remove the ovaries, in medical terms called prophylactic salpingectomy with delayed oophorectomy (Kyo et al., 2019).

Compared to traditional surgery, women who have only removed their fallopian tubes often report better quality of life (Gasparri et al., 2019). The delayed ovary removal (oophorectomy) still induces menopause, but using the two-step approach, it can be done closer to the average age of natural menopause (~age 51), potentially without increased cancer risk, although that is what these studies look to definitively determine.

Currently, an estimated 65% of BRCA carriers elect to remove their fallopian tubes and ovaries, so having more options to reduce risk and improve quality of life will not only impact current but also future generations of BRCA mutation carriers (Gasparri et al., 2019).

What carriers should consider

Current guidelines still endorse the combined fallopian tube and ovary removal for BRCA1 and BRCA2 carriers. This table highlights the current age range for the standard single surgery (rrSO) for BRCA1 and BRCA2 compared to the two-step approach. The right choice will look different for every BRCA carrier depending on their age, mutation status, family cancer history and lifestyle. It’s important to note that the current study on offer in BC is *not available* to BRCA2 carriers, however.

(Steenbeek et al., 2023)

What is fallopian tube and ovary removal-risk-reducing Salpingo oophorectomy (rrSO) exactly?

In this procedure, a single laparoscopic surgery is typically done between the ages of 35-45, depending on your BRCA mutation. This surgical option reduces ovarian cancer incidence by up to 96% and breast cancer incidence by up to 50% (Choi et al., 2021). With this risk reduction, women must however navigate surgical menopause, which may have symptoms that can be challenging to manage with or without hormone replacement therapy (HRT), depending on your healthcare provider's guidance. It Is recommended that hormone replacement therapy is gradually stopped around the average age of natural menopause (age 51) (Kaunitz et al., 2021).

What is fallopian tube with delayed ovary removal? (rrSDO)

This approach is being investigated in clinical trials globally and is now available in BC, for those eligible for the SOROCK study. In this approach, two laparoscopic surgeries are done between 5 and 15 years apart, depending on the BRCA mutation and the patient's age. First, the fallopian tubes are removed, which early research suggests results in an estimated 65% ovarian cancer risk reduction (Boerner et al., 2021). Compared to the single surgery, there are very few side effects associated with fallopian tube removal. The second surgery, which is completed closer to the age of natural menopause (age 51), involves removing both ovaries. Menopause is surgically induced, and HRT can take place for a short time to aid in the transition to menopause. Women may still experience both short- and long-term effects from induced menopause, and current studies are measuring experience outcomes to determine the benefits of waiting closer to natural menopause age (Gasparri et al., 2019). Two surgeries inherently carry more risk and recovery time than one; however, the quality-of-life benefits for BRCA carriers may make this approach the preferred method once we learn more from the current trials. A study published over 10 years ago also predicted that the two-stage approach would be a cost-effective alternative to standard rrSO, by improving quality-adjusted life expectancy at acceptable cost (Kwon et al., 2013).

The third option: no surgery

A portion of BRCA1 and BRCA2 carriers still elect not to have ovarian cancer risk-reducing surgeries. The risk of ovarian cancer before the age of 70 ranges from 17-44% depending on the BRCA mutation compared to 1.2% in the general population. (Kuchenbaecker et al., 2017). While there is a significantly increased risk, it is not a guaranteed cancer diagnosis in one's lifetime. Carriers who decide not to get risk-reducing surgeries should discuss the risks and benefits with their healthcare providers. It should be noted that at this time, there are currently no evidence-based ovarian cancer screening options in British Columbia (or anywhere in the world).

Current ongoing studies worldwide

PROTECTOR trial in the UK compares the outcomes of the two-step surgical approach to the traditional single surgery and those who do not have surgery (Gaba et al., 2020). The study is inclusive of women with BRCA1 and BRCA2 mutations, among others, who are at an increased risk of ovarian cancer. This study also measures the quality of life and satisfaction with the surgical outcomes.

TUBA-WISP II (short for Tubectomy with delayed oophorectomy as Alternative for risk-reducing salpingo-oophorectomy in high-risk Women to assess the Safety of Prevention) is a Dutch study focused on BRCA1 and BRCA2 carriers that includes participating centers from all over the world (Steenbeek et al., 2023). It compares the two-step surgical approach to the traditional single surgery. This study is primarily focused on quality of life rather than measuring the cancer-reducing efficacy of the two-step approach. The study also has an interactive aid module you can use to explore the pros and cons of different ovarian cancer risk-reducing options for both BRCA1 and BRCA mutation carriers.

SOROCk study is based in the United States and is limited to pre-menopausal BRCA1 carriers. The objective is to determine if carriers can benefit from the same ovarian cancer risk reduction by only removing fallopian tubes (Huh et al., 2022,). Similarly, to TUBA WISP II This study also aims to measure quality of life benefits reported by the participants receiving the two-step surgery compared to those who had the single surgery.

What is the opportunity now for BC women?

Clinical trials centred on this two-step approach have been inaccessible to BC women until now. The SOROCk study has partnered with UBC as a satellite study center. This means pre-menopausal BRCA1 carriers between the ages of 35-50 in BC now have the opportunity to join the study and have risk reducing surgery in Vancouver. Eligible participants will be able to choose between the standard risk-reducing bilateral salpingo-oophorectomy (removal of both fallopian tubes and ovaries) or salpingectomy followed by delayed oophorectomy (removal of fallopian tubes first followed by a second surgery to remove ovaries).

Both options are outpatient procedures meaning that participants can go home the same day after the surgery. Participants will be followed by the team before, during and after the surgeries and are expected to complete quality of life surveys and annual follow ups. This is an exciting step to having more risk-reducing options for BRCA carriers in BC.

While this study is currently only open to BRCA1 carriers, future studies will be open to BRCA2 carriers. To participate you need a referral from your family doctor, nurse practitioner, or if you are an existing patient at the Gynecologic Cancer Survivorship Clinic, you can get a referral from Dr Lesa Dawson. For more information concerning how to apply and eligibility criteria can be accessed here or by contacting the study’s research associate Wilfred Hui directly.

References

Boerner, T., Long Roche, K., Fiacco, E., Zuber, V., Di Micco, R., Gazzetta, G., Valentini, A., Mueller, M. D., Papadia, A., & Gentilini, O. D. (2021). Salpingectomy for the risk reduction of ovarian cancer: Is it time for a salpingectomy-alone approach? Journal of Minimally Invasive Gynecology, 28(3), 403-408. https://doi.org/10.1016/j.jmig.2020.09.020

Choi, Y.-H., Terry, M. B., Daly, M. B., MacInnis, R. J., Hopper, J. L., Colonna, S., Buys, S. S., Andrulis, I. L., John, E. M., Kurian, A. W., & Briollais, L. (2021). Association of risk-reducing salpingo-oophorectomy with breast cancer risk in women with BRCA1 and BRCA2 pathogenic variants. JAMA Oncology. https://doi.org/10.1001/jamaoncol.2020.7995

Gaba, F., Robbani, S., Singh, N., McCluggage, W. G., Wilkinson, N., Ganesan, R., Bryson, G., Rowlands, G., Tyson, C., Arora, R., Saridogan, E., Hanson, H., Burnell, M., Legood, R., Evans, D. G., Menon, U., & Manchanda, R. (2020). Preventing ovarian cancer through early excision of tubes and late ovarian removal (PROTECTOR): Protocol for a prospective non-randomised multi-center trial. International Journal of Gynecologic Cancer, 31(2), 286-291. https://doi.org/10.1136/ijgc-2020-001541

Gasparri, M. L., Taghavi, K., Fiacco, E., Zuber, V., Di Micco, R., Gazzetta, G., Valentini, A., Mueller, M. D., Papadia, A., & Gentilini, O. D. (2019). Risk-Reducing bilateral salpingo-oophorectomy for BRCA mutation carriers and hormonal replacement therapy: If it should rain, better a drizzle than a storm. Medicina, 55(8), 415. https://doi.org/10.3390/medicina55080415

Huh, W. K., Pugh, S. L., Walker, J. L., Pennington, K., Jewell, E. L., Havrilesky, L. J., Carter, J., Muller, C., Drapkin, R., Lankes, H. A., Demora, L., & Kachnic, L. A. (2022). NRG-CC008: A nonrandomized prospective clinical trial comparing the non-inferiority of salpingectomy to salpingo-oophorectomy to reduce the risk of ovarian cancer among brca1 carriers [SOROCk]. Journal of Clinical Oncology, 40(16_suppl), TPS10615. https://doi.org/10.1200/jco.2022.40.16_suppl.tps10615

Kaunitz, A. M., Kapoor, E., & Faubion, S. (2021). Treatment of women after bilateral salpingo-oophorectomy performed prior to natural menopause. JAMA, 326(14), 1429. https://doi.org/10.1001/jama.2021.3305

Kuchenbaecker, K. B., Hopper, J. L., Barnes, D. R., Phillips, K.-A., Mooij, T. M., Roos-Blom, M.-J., Jervis, S., van Leeuwen, F. E., Milne, R. L., Andrieu, N., Goldgar, D. E., Terry, M. B., Rookus, M. A., Easton, D. F., Antoniou, A. C., McGuffog, L., Evans, D. G., Barrowdale, D., Frost, D., . . . Lasset, C. (2017). Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA, 317(23), 2402. https://doi.org/10.1001/jama.2017.7112

Kwon J.S., Tinker A., Pansegrau G., McAlpine J., Housty M., McCullum M., Gilks C.B., Prophylactic salpingectomy with delayed oophorectomy as an alternative for BRCA mutation carriers. Obstet Gynecol 2013 Jan;121(1): 14-24. DOI: 10.1097/aog.0b013e3182783c2f

Kyo, S., Ishikawa, N., Nakamura, K., & Nakayama, K. (2019). The fallopian tube as origin of ovarian cancer: Change of diagnostic and preventive strategies. Cancer Medicine, 9(2), 421-431. https://doi.org/10.1002/cam4.2725

Steenbeek, M. P., van Bommel, M. H. D., intHout, J., Peterson, C. B., Simons, M., Roes, K. C. B., Kets, M., Norquist, B. M., Swisher, E. M., Hermens, R. P. M. G., Lu, K. H., & de Hullu, J. A. (2023). TUBectomy with delayed oophorectomy as an alternative to risk-reducing salpingo-oophorectomy in high-risk women to assess the safety of prevention: The tuba-wisp II study protocol. International Journal of Gynecologic Cancer, 33(6), 982-987. https://doi.org/10.1136/ijgc-2023-004377