• Ovarian Cancer
• 100 100 Answer Cancer Edition Ovarian Question Question Second Day
• What Are The Early Warning Signs Of Ovarian Cancer

L earning O bjectivesAfter completing this course, the reader will be able to:.Better appreciate the challenges faced in managing treatment of patients with ovarian cancer.Describe the factors that impact on the design of long-term treatment strategies for patients with relapsed ovarian cancer.Describe important disease management issues, including when to initiate treatment, which treatments to consider and why,and patient education.Access and take the CME test online and receive one hour of AMA PRA category 1 credit at. AbstractAdvances in the treatment and early detection of ovarian cancer have led to gains in 5-year survival rates, with 52% of womendiagnosed between 1992 and 1997 surviving 5 years or longer, compared with 41% of women diagnosed between 1983 and 1985.

Althoughapproximately 10%-15% of patients achieve and maintain complete responses to therapy, the remaining patients have persistentdisease or eventually relapse. These patients will generally undergo a series of treatments, each associated with progressivelyshorter treatment-free intervals. Nevertheless, median survival of patients with recurrent ovarian cancer ranges from 12-24months, demonstrating the chronic natural history of the disease. Advances in the treatment of ovarian cancer over the pastdecade have led to these improvements and have prompted oncologists to now view the management of patients with ovarian canceras an ongoing, long-term challenge.

Question: What is the WHO histological classification for ovarian tumors? World Health Organization: The World Health Organization (WHO) is one of several agencies overseen by the United Nations.

This shift in approach has raised important new questions regarding patient management,including the need to define trigger points for initiating or changing treatment (e.g., sequential increases in serum cancerantigen 125 levels, appearance of symptoms, or cumulative toxicities), anticipation of impending treatment decision points,recognition that the overtreatment of patients early in the disease process may adversely affect future treatment opportunities,and a renewed emphasis on patient education and participation in decision-making. This review will discuss these importantpatient management issues and will conclude with case studies illustrating two distinct treatment strategies (planning andsequencing) for the long-term management of patients with ovarian cancer.

I ntroductionThe 5-year survival of patients diagnosed with ovarian cancer has continued to improve over the past several decades, withmore than half of the patients diagnosed between 1992 and 1997 expected to live 5 years or more. These gains have been attributed, in large part, to broader access to expert surgical care, improvements in chemotherapy,and (to a lesser extent) to cancer screening. Of the patients who present with advanced disease (approximately 60%), approximately10%-15% achieve long-term remission; however, the remainder tend to undergo a progression of treatments. Thus, for the oncologist, a great deal of effort will be invested in the management and treatment of patients in relapse.The chronic nature of relapsed ovarian cancer has important implications for both oncologists and patients alike, includingrepercussions concerning treatment planning and patient education (e.g., setting realistic expectations). This review willdiscuss these important patient management issues and will conclude with case studies illustrating two distinct treatmentapproaches (planning and sequencing) to the long-term management of patients with relapsed ovarian cancer. C hallenges in O varian C ancerA number of important questions have emerged as a consequence of the need to plan for the long-term care of patients withovarian cancer, many of which revolve around treatment planning (Table 1).

Although 50% of patients treated with first-line therapy achieve a clinical complete response, half of these responderswill be positive for disease on second-look laparotomy. A further percentage of patients (50%) who are negative on second-looklaparotomy will eventually relapse , leaving a small proportion of patients initially diagnosed achieving long-term remission. These findings underscore theimportance of disease surveillance and of defining the point at which the tumor has relapsed and reinstitution of therapyis appropriate.

Disease Surveillance and Relapse DefinitionSurveillance options for monitoring disease activity include second-look laparotomy, physical examination (pelvic exam), serumcancer antigen 125 (CA-125) levels, and radiographic, magnetic resonance, or computed tomography imaging. Of these, a physicalexamination that includes a thorough pelvic exam is perhaps the most cost-effective surveillance option. Additionally, CA-125,a serum marker of the presence and severity of ovarian cancer, can be monitored at intervals. However, there can be a poorcorrelation between disease burden and CA-125 concentration in some relapsing patients. Additionally, abnormally elevatedor rising CA-125 levels may predate the onset of symptoms by many months or even years. Finally, patients often undergo orrequest imaging as a means of monitoring for disease recurrence.Although myriad tools are available to monitor disease activity, the timing of treatment initiation can be confounded by anumber of factors, including interpretation of CA-125 findings, ambiguous test results, and a lack of consensus for when relapsehas occurred.

Relapse is defined by some clinicians as a sequential increase in serum CA-125 or levels greater than some arbitraryvalue such as 100 U/ml. Although serum CA-125 is often used to guide treatment decisions, patients may remain asymptomaticfor extended periods despite exhibiting very high CA-125 levels. Additionally, some patients experience a symptomatic recurrencewithout suggestive changes in CA-125 marker levels or confirmatory imaging.

In such cases, a combination of positive surveillancefindings may confirm initial suspicions; alternatively, the patient may require further rigorous follow-up.Traditional clinical measures of relapse include disease progression, usually defined as a 25% or greater increase in tumorsize, appearance of new lesions, or death. Applying this definition to patients enrolled in clinical trials (e.g., GynecologicOncology Group Study 111), approximately 7% of patients will progress within the initial 3 months of receiving cisplatin/paclitaxel,while 13%-14% of patients will progress within 6 months of randomization (Fig. In Study 111, the average patient experienced clearly defined progression within approximately 18 months of randomizationto cisplatin/paclitaxel therapy. Clearly defined progression triggers a decision for further treatment based on factors including the time interval sincecompletion of initial chemotherapy. The observation of variable patient responses based on the duration of this interval hasled to a definition of relapsed patients based on the predicted platinum sensitivity of the tumor. Patients who progress onfirst-line therapy or relapse within 3 months of treatment are considered to be platinum refractory. Patients who respondto primary treatment and relapse within 6 months are considered platinum resistant, whereas those who relapse more than 6months after completion of initial therapy are characterized as platinum sensitive.

Platinum-Free IntervalAccording to current dogma in ovarian cancer treatment, the potential for patient sensitivity to platinum is perhaps the mostimportant factor in planning subsequent treatment. Tumor response rates are directly related to the platinum-free intervalamong all of the novel agents currently used in second-line therapy –. For instance, the range of antitumor responses in platinum-sensitive patients receiving topotecan is 19%-33% , , compared with 12%-19% for patients who are platinum resistant (Table 2) , –. A comparable pattern of responses has been observed with other novel agents in patients with recurrent ovarian cancer , –. As a result of these findings, an important goal of treatment is to extend the platinum-free interval for all patients,regardless of platinum sensitivity. One explanation for the consistent relationship between tumor response and platinum- or treatment-free interval is tumor resistance(e.g., P-glycoprotein-mediated multidrug resistance). As noted previously, the majority of patients relapse following an initialresponse to therapy and develop disease that is more drug resistant than at first-line therapy.

Tumor resistance in ovariancancer may be acquired or intrinsic. In acquired resistance, tumors become resistant to treatment under the selective pressureof a specific agent. However, acquired resistance is frequently unstable and can be lost over time. Therefore, the longer the treatment-free interval, the greater the chance for tumors to lose acquired resistance.In cases in which patients develop resistance to a specific agent (e.g., cisplatin), the application of a non-cross-resistantagent (e.g., topotecan) may offer an opportunity for tumor response. Because many of the agents used in second-line and salvagesettings have disparate mechanisms of action and are non-cross-resistant with platinum and/or paclitaxel, there are a varietyof options to offer patients. Moreover, the use of a nonplatinum agent at first relapse, for instance, can lower the probabilitythat tumors will become increasingly resistant to platinum retreatment.

The results of a study by Kavanagh et al. suggest that extending the platinum-free interval improves patient outcomes by increasing the sensitivity of tumors to subsequentreintroduction of platinum. In that study, the use of an agent not cross-resistant with platinum (taxane) at relapse sensitizedpatients’ disease to the reintroduction of carboplatin. Another potential benefit of extending the platinum-free intervalis avoiding potential cumulative toxicities. Cumulative ToxicitiesTreatment-related toxicities increase with increasing numbers of treatments.

Because the treatment-free intervals progressivelynarrow or disappear with the introduction of each new therapy, planning for cumulative toxicity takes on greater significanceas the number of salvage regimens increases. For instance, the reintroduction of platinum at first relapse may lead to cumulativemyelosuppression (particularly thrombocytopenia) and neurotoxicity. Thus, patients receiving platinum at first relapse mayenter further therapies with compromised bone marrow reserves and consequently may not achieve maximal clinical benefits fromthese other active therapies. Potentially suboptimal tumor responses may be attributed to the administration of lower, potentiallysubtherapeutic dose levels or because of dose omissions (see Dunton et al. In this issue for an in-depth review of cumulative toxicity, pp 11-19 ). Likewise, the use of or need for blood product support may result in a delay in initiating subsequent courses of therapyor reductions in subsequent dose levels. In summary, although in clinical practice all patients entering on therapy for ovariancancer have hope for complete response and long-term remission, clinicians and their patients should be realistic about thelow probability of achieving these outcomes.

As a result, caution should be exercised that subsequent rounds of interventionare not jeopardized through the pursuit of overly aggressive treatment at first relapse. Patient/Disease FactorsFor newly diagnosed patients, a number of patient and disease factors are important in the rational design of a treatmentplan, including disease stage, volume of residual disease following cytoreductive surgery, performance status, sites of metastases(e.g., liver), presence of ascites, and tumor histology. Of these prognostic factors, disease stage, residual tumor burden,and performance status have been the best studied. Survival is inversely related to disease stage; patients with stage I,II, III, and IV ovarian cancer have median 5-year survival rates of approximately 93%, 70%, 37%, and 25%, respectively. Thus, in patients with advanced inoperable tumors, chemotherapy with a good tolerability profile may be used to controlsymptoms. In these patients and in those who undergo optimal debulking surgery (approximately 60%), platinum-based therapywith paclitaxel is the standard first-line approach.Intuitively, optimal versus suboptimal (residual disease ≥1 cm) cytoreduction represents another important prognostic factorin the survival of patients with ovarian cancer.

Patients with minimal residual disease have a greater probability of achievinga remission following systemic chemotherapy, have a longer time to relapse, and live longer than patients with large-volume,bulky residual disease. In one study of patients with stage IV disease, the overall median survival for optimally debulkedpatients was 32 months, compared with 16 months for suboptimally debulked patients. In a similar study in patients with stage IV disease, median survival for optimally cytoreduced patients was 38 months,compared with 10 months for suboptimal residual disease. Other studies have demonstrated the importance of surgical debulking as an independent prognostic indicator for survival,. However, the potential benefits of surgical debulking and the prognostic importance of disease volume have not been prospectivelystudied in recurrent disease.Performance status is another useful prognostic indicator of survival in patients with advanced ovarian cancer.

In a studyby Bristow et al. , overall median survival was highly correlated with performance status ( p = 0.002). The prognostic value of performance status has also been demonstrated in other studies.

Patient EducationEducating patients regarding the natural history of their disease and the treatment options available empowers them to partnerwith their physician in the decision-making process and to better meet the challenges of the disease. Because it is likelythat patients will receive a series of three to five treatment regimens over the course of the disease, proactive planningand shared decision-making are vital to ensure the best possible outcome. Additionally, proactive planning allows for theuse of a treatment regimen that offers the greatest efficacy benefit while balancing considerations for patient lifestyleand potential cumulative toxicities. Consideration should also be made for scheduling chemotherapy into the patient’s dailyroutine; that is, discussing with the patient issues concerning when she is better able to comply with treatments and to toleratecertain toxicities.

Additionally, educating patients on the toxicities associated with each regimen and toxicity interventionsand management are vital to ensuring that therapeutic dose levels are administered in a timely manner and maintained throughoutthe recommended duration of treatment.Another critical aspect of education involves the early establishment of realistic expectations for patients. Although onlya small percentage of patients will achieve long-term disease remission, the vast majority will experience a series of treatments,remissions, and recurrences. Additionally, patients should be informed about the possibility of achieving a late clinicalbenefit despite a lack of early evidence that a clinical response will be achieved (i.e., reduction or normalization of CA-125levels). Further, educating patients on the benefits of stable disease is an important lesson in the context of this chronicdisease. The clinical value of stable disease in ovarian cancer has been established. Survival among patients who achieved stable disease was statistically comparable with those who experienced a partial responseto topotecan.

Thus, stable disease may offer equal clinical benefit compared with partial tumor responses in patients withrelapsed ovarian cancer. In the context of maintaining stable disease, the choice of an agent that can be administered atdisease progression (i.e., no cumulative toxicities) would be desirable. T reatment S trategies in O varian C ancer M anagementTreatment strategies will be presented that summarize two approaches in the long-term management of patients with relapsedovarian cancer.

The first strategy offers a review of a commonly practiced treatment sequence, whereas the second strategyprovides an alternate sequence plan with greater recognition of the chronic nature of relapsed ovarian cancer.As shown in Figure 2, the commonly practiced treatment sequence begins with carboplatin or cisplatin plus paclitaxel as first-line therapy. Themedian progression-free interval (PFI) in stage III/IV ovarian cancer patients receiving platinum (cisplatin/carboplatin)with paclitaxel ranges from approximately 18-22 months ,. Because most patients respond well to platinum and paclitaxel in first-line therapy as measured by objective response ratesand PFI, the median or average patient is considered platinum sensitive and usually is re-treated with platinum and taxanetherapy at first relapse. Response rates of up to 84%-91% have been reported at first relapse , ; however, the time to progression generally shortens with consecutive therapies. Provided the patient continues to respondto treatment, each successive response or disease remission is typically shorter in duration than the previous one. Following each disease recurrence, the patient will continue to receive a series of new treatments, including, but not limitedto, oral etoposide at second relapse, liposomal doxorubicin at third relapse, topotecan at fourth relapse, and gemcitabineat fifth relapse.

However, cumulative toxicities associated with most, but not all, of these treatment choices may lead toa diminution in the number of downstream options ( Dunton et al. For instance, retreatment with platinum and paclitaxel at first relapse can result in cumulative neurotoxicity and myelosuppression,which may limit the available treatment options on subsequent relapses.

In the treatment strategy proposed in Figure 2, etoposide is recommended at second relapse, with the goal of extending the platinum-free interval. However, although etoposideis convenient and generally well tolerated, it has also been associated with an increased risk for secondary leukemias. Uponrelapse on etoposide, patients continue on therapy with liposomal doxorubicin. Although liposomal doxorubicin affords patientsthe opportunity to further extend the platinum-free interval, cumulative palmar-plantar erythrodysesthesia (PPE) often limitsthe number of cycles administered. Severe (grade 3/4) PPE occurs in up to 23% of liposomal doxorubicin-treated patients andis managed by dose reduction, delay, or discontinuation of therapy. Viewed as a whole, this treatment sequence can be seriously debilitating to the overall health and well-being of the patient.According to the sequence illustrated in Figure 2, the patient will typically receive topotecan at fourth relapse.

However, significant disadvantages to withholding topotecanuntil fourth relapse are the more demanding dosing schedule and bone marrow toxicity. The standard regimen of 1.5 mg/m 2/day for 5 consecutive days of every 21-day cycle is more demanding of the patient at a time when she is less likely to beable to tolerate therapy, irrespective of how active the agent is in managing the disease. Moreover, whereas the bone marrowtoxicity associated with topotecan is noncumulative and can decrease over subsequent courses of therapy , it arrives at a time when the patient has undergone a series of myelosuppressive treatments and enters on treatment withdepleted bone marrow reserves.Finally, the patient receives gemcitabine at fifth relapse. Gemcitabine is convenient and, like topotecan, has no cumulativetoxicity.

However, gemcitabine demonstrates a lower activity level than other agents in patients with recurrent ovarian cancer.In summary, the cumulative toxicities incurred with the treatment schema illustrated in Figure 2 may adversely affect patient outcomes, including quality of life. Because this strategy does not adequately recognize thechronic nature of relapsed ovarian cancer, alternate approaches to the long-term management of patients should be pursued.An attractive but unproven alternate approach to that described in the first strategy is depicted in Figure 3. As illustrated in this matrix, initial therapy continues to include carboplatin or cisplatin plus paclitaxel. However, ratherthan re-treating the patient with platinum and a taxane at first relapse, the patient receives topotecan. The efficacy oftopotecan is comparable to that of single-agent platinum in this setting. Topotecan yields overall response rates of 13%-33%and a PFI of approximately 2.5-8.8+ months, depending on the degree of platinum sensitivity ( Herzog pp 3-10 ) –,.

An additional 23%-48% of patients achieve stable disease, which has also been associated with significant patient benefits(i.e., improved survival) ,. The rationale for moving topotecan forward in the treatment sequence is several-fold. First, there is a lack of cumulativetoxicity associated with topotecan.

Although the main toxicity associated with topotecan is myelosuppression, it is short-lived,noncumulative, and manageable. Furthermore, the platelet toxicity associated with topotecan wanes in severity over the durationof treatment. Additionally, as might be expected, the severity of myelosuppression with topotecan correlates with the number of priortreatments and is worsened in patients who are heavily pretreated (Fig. Therefore, the best opportunity to use topotecan is at first relapse, when patients are less heavily pretreated. Patients are also better able to comply with topotecan therapy when they are less heavily pretreated.

Because myelosuppressionis noncumulative and short-lived, the use of topotecan at first relapse should not diminish downstream opportunities withplatinum, etoposide, liposomal doxorubicin, gemcitabine, or paclitaxel (Fig. Because topotecan demonstrates a lack of cumulative toxicity, the agent can be used to treat patients until disease progression,allowing patients to extend the treatment benefits of topotecan. The long-term benefits of topotecan treatment have been establishedin patients with ovarian cancer treated over the long term.Finally, patients may benefit from an extension in the platinum-free intervals in terms of the tumor response rates that canbe achieved with further platinum treatment. Notably, topotecan has a distinct mechanism of action and has not shown cross-resistancewith platinum or paclitaxel.

In a study by ten Bokkel Huinink et al. , topotecan was active in platinum- and paclitaxel-resistant tumors, with an overall response rate of 20%. The non-cross-resistanceof topotecan to first-line therapy and data indicating that extending the platinum-free interval facilitates platinum reintroductionsuggest that this agent is a good candidate for treatment of patients at first relapse.In this alternate sequence, after relapse on topotecan therapy, the patient receives platinum rather than the oral etoposiderecommended in the initial strategy. Tumor responses have been observed in patients re-treated with platinum following topotecantherapy.

Additionally, according to this sequence (and the first sequence), liposomal doxorubicin is reserved for treatment of thirdrelapse, thus delaying the onset of cumulative PPE. However, the relative convenience of once-monthly administration of liposomaldoxorubicin is an important factor in selecting salvage agents.

Finally, etoposide is recommended at fourth relapse becauseof its convenience and because secondary leukemia is less of an issue later in the disease course, whereas taxane retreatmentor gemcitabine is selected for fifth relapse due to unique mechanisms of action and good tolerability, albeit with less provenefficacy. S ummary and C onclusionsThe chronic natural history of relapsed ovarian cancer has important implications for both oncologists and patients in termsof treatment planning and patient education (Table 3). To optimize the management of patients over the long term, clinicians should recognize that ovarian cancer and the patient’sresponse to treatment take a variable course that requires tailoring disease management to individual patient needs. Additionally,clear definitions and consensus guidelines are needed to provide oncologists with the necessary information to anticipateimpending decision points in the natural history of the disease. These tools will help guide the oncologist and the patientthrough the treatment decision process. Also driving treatment decisions is the desire to manage treatment-associated toxicitiesand extend the platinum-free interval, with a focus on monitoring for potential cumulative toxicity in these sometimes heavilytreated patients. Finally, the education of patients takes on greater importance, including apprising them of the benefitsof stable disease and partial tumor responses, and maintaining realistic expectations for lasting disease remission and survival.A greater appreciation of these challenges and issues will augment our ability to offer the best possible treatment strategythat maximizes clinical end points in patients with ovarian cancer.

© Maggie O'NeillMaggie O'NeillRose Marie Jackey is sitting in her hospital bed at Mount Sinai Hospital in New York City awaiting her monthly chemotherapy infusion—a treatment she's been getting each month for the past three years.It's what she and her doctors call 'maintenance therapy,' which, according to Jackey, makes it sound much more enjoyable than it actually is. 'I'm not getting a facial here,' she jokes. 'It sounds like you're on some kind of wonderful fresh fruit diet or something.' While it's a less invasive version of chemo, it still has some less-than-pleasant side effects, like mouth-blistering, overall fatigue, and an increased risk of kidney issues and blood clots.But that 'maintenance therapy,' however unpleasant, has kept her healthy since her second surgery to treat a rare, aggressive form of ovarian cancer in October 2016—one that had already recurred despite chemotherapy once before, and one that may come back again. In fact, Jackey being alive and well today is a sort of 'miracle,' in itself, her doctor says—and is a testament to just how dangerous her cancer was, and how far she's come since first being diagnosed.Jackey first knew something was wrong when she couldn't pee while on vacation in March 2016. © Alex SandovalShe asked her female friends, with whom she was traveling, what they thought was going on.

They believed she just had a urinary tract infection. Her general practitioner based in New York gave her the same answer and prescribed antibiotics.But two days later, when the antibiotics hadn't helped her situation, Jackey knew something bigger was up. She called her doctor in New York again, who told her to come home immediately.Back in New York, Jackey saw a urologist, who misdiagnosed her a second time. He reduced her symptoms to signs of aging, diagnosing her with urinary incontinence, or a loss of bladder control. Jackey was less than thrilled with his evaluation. “It was awful.

It was sexist,” she recalls. But she used the cream he gave her, hoping to alleviate her discomfort. After two days of following his instructions, though, she still couldn’t pee without contorting her body and physically 'jumping' to force the pee out.

Ovarian Cancer

'I was in pain,' she says.With that, Jackey called her doctor a third time, and he told her to go to the emergency room. She went to one on Long Island, where she lives, but still didn’t get any answers as to what was going on with her body. “No one examined me, nothing. They just put a catheter a tube that drains urine in.” © Getty(Stock image)Finally, after days of being in pain and having trouble urinating, she found an ob-gyn who immediately confirmed that something was wrong. After looking at the results of a sonogram, the ob-gyn told Jackey to bring her husband into the evaluation room to hear the results.

'She just kept saying over and over again, ‘I’m so sorry. I’m so sorry. You have a huge tumor blocking your urinary tract, and I think it’s cancer,' says Jackey.The next day, Jackey had her ovaries and uterus removed, and her doctor biopsied the tumor.The day after her operation, the first thing Jackey asked her doctor, Konstantin Zakashansky, MD, a gynecologic oncologist at Mount Sinai in New York City, was whether or not she had cancer.

Zakashansky's response: 'Probably,' but they were still waiting on the biopsy results to know exactly what they were dealing with.Those results confirmed that it was cancer—specifically, ovarian clear cell carcinoma, an especially rare type in the US, accounting for just 5–10% of all ovarian carcinomas in North America, according to. Ovarian clear cell carcinoma is associated with endometriosis (which Jackey had), and average survival rates for the illness depend on the stage the cancer is in when it is diagnosed. Women who are diagnosed with advanced ovarian clear cell carcinoma 'have poor survival,' the research in Gynecologic Oncology says, adding that they are often chemotherapy-resistant.Gallery: 50 foods that can lower your cancer risk (The Daily Meal). Ovarian clear cell carcinoma is usually diagnosed when women are in their forties, Dr. Zakashansky tells Health. Jackey was diagnosed in her sixties, he says, explaining that made the case even more rare. Because ovarian clear cell carcinoma is so rare, doctors don’t know as much as they’d like about the best way to treat it.

100 100 Answer Cancer Edition Ovarian Question Question Second Day

“We’re dealing with rare disease. There’s no randomized data, at all, specifically addressing the best treatment options for clear cell ovarian cancer,” says Dr. “You kind of have to individualize treatment plans.”At first, doctors were hopeful that the procedure she had in March combined with three months of chemotherapy would take care of the problem.

But a scan in September revealed the cancer was also in her lymph nodes—and that it might be in her liver too. Her lymph nodes had been tested for cancer only four months earlier, and they were clean then, which meant Jackey's cancer continued to grow even while receiving chemotherapy.That's the thing about Jackey's specific type of ovarian cancer, says Dr. Zakashansky: When it recurs, the chances of survival are not good.

'It’s terrible. In the recurrent setting, those patients do not live very long at all.

They generally do very poorly,” says Dr. Zakashansky.Jackey's prognosis seemed especially grim, says Dr.

What Are The Early Warning Signs Of Ovarian Cancer

Zakashansky, since it appeared she was chemo-resistant. 'She had recurrence while she had chemotherapy. It kind of looked bleak at that point,” explains Dr. © GettyOvarian cancer vaccine under research.After getting multiple opinions from New York City’s biggest hospitals on whether or not she should have a second surgery to remove the cancer from her lymph nodes, Jackey learned many doctors believed any further surgeries would be 'pointless' and possibly dangerous to Jackey—except for Dr. There was controversy over whether surgery is the right way to go because she had a very short interval to recurrence.

Usually, we operate on patients that have long intervals,” says Dr. (FYI: Having “a short interval to recurrence” means the cancer came back quickly.) Still, Dr. Zakashansky was the first to recommend another operation, arguing that if anything at all could be done for his patient, surgery was it.Jackey had a second surgery in October 2016, in which she had cancerous lymph nodes removed.

Luckily, during the procedure, doctors confirmed that Jackey's cancer hadn't spread to her liver, which had been a concern after the September CAT scan.In all, her second surgery was successful. “Most of the surgery was just very tedious, careful dissection, removing all the enlarged lymph nodes. At the end of the procedure, she was completely free of disease,” says Dr. Zakashansky.Then came the question Jackey still lives with today: When will her cancer come back, if at all? © Maggie O'NeillMaggie O'NeillThat question was what prompted doctors to put Jackey on monthly infusions of a chemotherapy drug called Avastin, to reduce her chances of recurrence. Her doctor thought this was the best course of action, since her cancer recurred after her first treatment plan failed.Living with an indefinite chemotherapy prescription sounds scary—but not as scary, in some ways, as considering what might happen if she stops the monthly infusions, and the very aggressive cancer that managed to grow while she was receiving chemotherapy the first time around comes back for a third time.Still, Dr. Zakashansky says he and Jackey have been talking about the possibility of quitting the maintenance therapy.

She’s been doing so well and remained disease-free for so long that it’s tempting. “We’ve been talking about it. She’s nervous. Everybody’s nervous about stopping it,” says Dr.

Zakashansky, weighing the options. “Maybe we can stop treatment and everything’s going to be great, but how horrible everyone’s going to feel if we stop and everything comes back.”Jackey's current situation—that her cancer hasn't recurred in three years—is a promising indicator of how she might do off of chemotherapy, mainly because doctors don't really understand why it hasn't recurred yet. “I can’t think of a case in which the patient failed primary treatment, recurred extensively, and continued doing so well,” says Dr. That's because 70–80% of the time, ovarian clear cell carcinoma that has recurred in the past comes back again.Dr. Zakashansky chalks this up to how drastically different the disease can look in different people. 'That’s the thing about ovarian cancer,' he says. 'If you look at the numbers, they look terrible.

But it’s a dramatically different disease, even though everyone gets treated the same.' Gallery: 50 signs of poor health no-one over 50 should ignore (Best Life). Jackey herself has a number of theories as to why she’s done so incredibly well, despite her cancer's recurrence, crediting positive thinking, healthy eating, exercise, her faith, and her support system, as well as her work, which she's continued to do throughout her disease. (Jackey only missed two meetings—one in March and one in October, for each of her surgeries—but worked steadily despite her treatments).As for her health and outlook on life, Jackey insists on looking to the future—even though her future is uncertain.

Neither she nor Dr. Zakashansky know what will happen when and if she stops getting a monthly chemotherapy infusion, but she’s planning a vacation for 2022 despite that uncertainty.“Ovarian cancer in general doesn’t have good prognosis. But you look forward,” she says. “You never say, ‘Why me?’ I said, ‘Why not me?’ I’ve had a great life, why shouldn’t I have this disease?

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