Leah K. Lawrence

NINA BEATY, a small cell lung cancer survivor, says she is alive because of immunotherapy.

Nina Beaty was one of the last patients to enroll in a clinical trial testing immunotherapy for the treatment of small cell lung cancer (SCLC) in May 2015 at Memorial Sloan Kettering Cancer Center (MSK) in New York City, where she resides. Now, she credits the trial for saving her life. The trial tested the drug Opdivo (nivolumab), an immune checkpoint inhibitor that blocks a pathway in cancer cells called PD-1, which is a protein that prevents T cells from recognizing and attacking cancer cells.

In Beaty’s case, within four weeks of initiating treatment with Opdivo, the 63-year-old woman’s tumor had shrunk by almost half. Now, nearly two years later, she continues to do well.

“When my oncologist saw my results, she was amazed,” Beaty recalls. “She gave me a huge hug out of sheer joy when sharing the news. I’ll never forget that moment of celebration for all of us in the room.”

Immunotherapy treatments, another class of drugs called PARP inhibitors and a DLL3-targeted antibody-drug conjugate called Rova-T (Rovalpituzumab tesirine) are among a group of new therapies showing early promise in clinical trials for the treatment of patients with SCLC, a disease that has had little improvement in prognosis in the last 25 years.

Small cell lung cancer, the most aggressive form of lung cancer, is named for the small, oval-shaped cancer cells seen under a microscope. It accounts for about 10 to 15 percent of all lung cancers in the United States.

Unlike non-small cell lung cancer, it spreads earlier and is often diagnosed at a time beyond the point where surgery could be considered — leaving chemotherapy as the only standard option. SCLC usually starts in the bronchi, and then quickly grows.

“In the patients who come to see me in clinic with SCLC, they describe having developed symptoms quickly, with a significant change in their normal activities in a short period of time,” says Lauren Averett Byers, M.D., assistant professor in the Department of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center in Houston.

Most lung cancers do not cause any symptoms until they have spread, but some patients with early lung cancer do have symptoms. Among the most common symptoms seen in patients with SCLC are worsening cough, shortness of breath and labored breathing. However, SCLC can also be diagnosed incidentally on chest imaging with patients experiencing no symptoms at all, as was the case with Beaty. The disease occurs more commonly in people with a history of smoking, but there are rare cases in individuals who have never smoked. Once SCLC is discovered, it is typically classified as either limited stage — disease confined to one side of the chest &mdash; or extensive stage &mdash; where tumors have spread to the opposite side, or beyond the chest.

Patients with limited-stage disease, representing about 40 percent of all diagnoses, can be treated with radiation to the chest, chemotherapy or surgery, and have a median survival of 16 to 24 months. In patients with extensive-stage disease, the disease has become too sizeable for radiation treatment, Byers explains. These patients are usually treated with chemotherapy alone, and have a median survival of between 6 and 12 months.

Due to the high rate of brain metastasis, a technique called prophylactic cranial irradiation (PCI) is a standard treatment for all patients with SCLC who respond to chemotherapy. PCI has been shown to improve survival to a significant degree in patients with either limited or extensive stage disease. However, it may be best to use in younger patients, because some study results have shown PCI-related neurotoxicity, such as dementia or walking disturbance, more frequently in older patients.

When Beaty learned about her SCLC, she was diagnosed with limited-stage disease and underwent traditional treatment with platinum-based chemotherapy and radiation. Her cancer responded to treatment, but within a year her follow-up imaging scans showed that her original tumor was growing back, and the disease had spread to other parts of her body.

“SCLC is a type of cancer that responds well initially to chemotherapy and radiation,” Byers says. “Often we see a lot of shrinkage from the treatment and patients notice an improvement in symptoms, but the challenge remains that for almost all patients, the disease is going to come back at some point.”

Only about 10 percent of patients with SCLC remain disease-free two years out from the start of therapy.

Knowing that she was running out of options, Beaty’s doctors referred her to MSK to enroll in a clinical trial testing experimental therapies.

For years, researchers have sought more effective treatments for patients whose SCLC has progressed after their initial treatment, says Charles M. Rudin, M.D., Ph.D., chief of the Thoracic Oncology Service at MSK.

Currently, topotecan is the only FDA-approved therapy for recurrent SCLC. The chemotherapy drug has been shown to improve overall survival, quality of life and symptom control, compared with best supportive care.

“A number of other drugs are currently being used for these patients that have been adopted by the National Comprehensive Cancer Network guidelines, including drugs like temozolomide, and, more recently, a combination immunotherapy regimen of the drugs Opdivo and Yervoy [ipilimumab],” Rudin says.

The combination of Opdivo and Yervoy has been tested in several other solid tumors and has shown improvements in outcomes for certain patients.

To treat her cancer, Beaty was enrolled in a trial for patients with SCLC who had their tumors progress after prior therapy. Called CheckMate-032, it tested Opdivo alone or in combination with Yervoy, which is a different type of immunotherapy called a CTLA-4 inhibitor. Beaty was treated on the Opdivoalone arm. Published results of the CheckMate-032 study showed that both Opdivo alone and with Yervoy had antitumor activity in patients with relapsed SCLC.

These results were similar to those from another trial also testing Opdivo with or without Yervoy that also showed that Opdivo alone or in combination with Yervoy was associated with antitumor activity and durable responses.

The KEYNOTE-028 trial tested another immune checkpoint inhibitor, Keytruda (pembrolizumab), in patients with advanced-stage SCLC that is positive for PD-L1, a ligand on the immune and tumor cells that normally binds to the drug’s target. About one-third of patients treated with Keytruda in the study had their tumors respond to treatment.

While they show promise, immunotherapy drugs can cause serious side effects, and patients on these treatments need to be carefully monitored. Nonetheless, in most patients, they are well tolerated, with severe side effects seen less frequently than is typical with chemotherapy, according to Rudin. Many toxicities that do occur are specific to treatment with immunotherapies and the stimulation of the immune system.

Although these side effects can be serious, they can usually be managed in patients with close follow-up, he adds.

“The real excitement with immunotherapy, in my mind, is when we do get responses, they can, in some cases, be quite durable,” says Rudin, who treated Beaty on the CheckMate-032 clinical trial. “Nina is coming up on two years of treatment. She has an excellent quality of life and a continued remarkable response.”

However, most patients with SCLC, like those with many other tumor types, unfortunately do not currently respond to immunotherapy. In the CheckMate-032 trial, the objective response rate was only 10 percent for patients treated with Opdivo alone, and about 21 percent for the combination group. For those patients who do respond, clinicians do not yet know the optimal duration of immunotherapy treatment. For example, Beaty has been told that she may need to continue to undergo immunotherapy infusions in the foreseeable future.

“We do have patients who have had to go off of immunotherapy because of adverse effects whose tumors have remained in remission, in rare cases for many years,” Rudin says. “We are always a bit afraid to quit when patients have good success and tolerance to a drug.”

Researchers continue to conduct studies of immunotherapy treatments in order to identify which patients will respond to therapy and to find ways of getting more patients to respond.

Another exciting area of research for patients with SCLC is the use of PARP inhibitors. A PARP inhibitor is a drug that blocks an enzyme in cells called poly ADP ribose polymerase, which helps repair DNA when it becomes damaged. For patients with cancer, blocking PARP may help keep cancer cells from repairing their damaged DNA, consequently causing the cancer cells to die.

“In early studies, we found that SCLC has high levels of the protein PARP, and when we block it with a drug that inhibits PARP, that small cell dies,” Byers says.

One preclinical study conducted by Byers and colleagues showed an equal decrease in growth of SCLC cells using a PARP inhibitor as is seen with standard chemotherapy. When used together, the two approaches may work even better, says Byers. In another recent study, Byers, Rudin and colleagues tested a PARP inhibitor called veliparib. Patients with previously treated SCLC were treated with the chemotherapy drug temozolomide with or without veliparib. The combination increased response rates almost threefold compared with chemotherapy alone.

“We also found biomarker testing that could help us predict who would get the most benefit from a PARP inhibitor,” Byers says.

She and colleagues at MD Anderson Cancer Center, as well as several other cancer centers, continue to design and launch clinical trials investigating PARP inhibitors in patients with SCLC, along with tests to identify patients mostly likely to respond, in the hopes of getting at least one PARP inhibitor approved for the standard care of patients with relapsed SCLC.

Research into immunotherapies, PARP inhibitors, and other new treatments continue to provide promising new approaches to the treatment of SCLC, and hope to patients living with the disease.

Beaty acknowledges that she has beaten the odds by surviving almost two years since her SCLC spread outside of her chest. As a way of giving back, she has applied her background as an art therapist to work with patient support groups that help provide guidance and support to other patients with SCLC.

One of the most encouraging resources she found is a group called Imerman Angels, which provides one-on-one cancer support. Through the group’s website, patients can fill out a support request form where they can enter information such as their diagnosis, age and gender. They are then matched with someone to speak with, who has dealt with the same or similar diagnosis, about their personal diagnosis and journey.

“As a newly diagnosed person, you hear that the average survival is 3 to 6 months, and you look to find other patients with a similar experience as you and discover that there aren’t many around,” Beaty says. “A couple of weeks after contacting Imerman Angels a man called me and said he had SCLC and had survived two years. Hearing that surviving two years was possible made me burst into tears. It was the first time that I was given some hope and realized that I might have a future after all.”

Now, Beaty is the survivor, and she credits it all to immunotherapy.

Articles

Treatment options on the horizon offer hope to patients with small cell lung cancer.

Finding New Targets for Small Cell Lung Cancer

ERICA BRITTON has a genetic mutation associated with risk for both breast cancer and melanoma. - PHOTO BY RACHEL FESKO

WHEN ERICA BRITTON, 31, was diagnosed with melanoma at the age of 23, her family history of ovarian cancer prompted her physicians to test her for inherited mutations in the BRCA1 and BRCA2 genes. Inherited mutations in these genes, or germline mutations, are most commonly associated with increased risk for breast cancer and ovarian cancer; however, some research has also linked the mutations to an increased risk for certain skin cancers, including melanoma.

Melanoma is a form of skin cancer in which cancer cells form in melanocytes, or the cells that color the skin, such as moles. In 2016, it is estimated that more than 76,000 new cases of melanoma were diagnosed. The majority of cases are diagnosed at an early stage, and these patients have a five-year survival rate of greater than 90 percent. Although melanoma starts in the skin, it can spread, or metastasize, to other parts of the body. Patients diagnosed with metastatic melanoma have a five-year survival rate of about 18 percent.

About 8 percent of people diagnosed with melanoma have a first-degree relative who has also been diagnosed. Even fewer — about 1 to 2 percent &mdash; have two or more relatives with melanoma. These patients may have familial melanoma.

“Cases of inherited melanoma are extremely rare,” says Lynn M. Schuchter, M.D., chief of the division of hematology/ oncology and C. Willard Robinson Professor of Hematology-Oncology at Penn Medicine. “The vast majority of melanoma is sporadic.”

Everyone is at some risk for sporadic (non-inherited, or random) melanoma, but there are certain factors that increase the likelihood of getting the disease. People with fair skin that freckles or burns easily, people with blue, green or light-colored eyes, and those with red or blond hair are all at increased risk. In addition, long periods of exposure to natural sunlight or artificial ultraviolet (UV) radiation, like from a tanning bed, can increase risk. Finally, having several large or many small moles, or having a family history of unusual moles, can increase the risk for melanoma.

All of these risk factors are relevant in familial melanoma, but most familial or hereditary cancers are caused by certain germline (inherited) mutations.

“There is an increased risk for developing melanoma associated with gene mutations passed from generation to generation, but there is also risk associated with other things shared by families,” explains Pauline Funchain, M.D., a medical oncologist at Cleveland Clinic, in Ohio. “These shared things include other predisposing factors for melanoma like blond or red hair, fair skin, blue or green eyes, or shared activities like boating or other outdoor activities.”

“I am all about sunscreen and UPF clothing and hats. I don’t live my life in fear, but I am very careful about being outside.” — ROBYN COOK - Photo by PHOTO BY HEIDI SHUB

Robyn Cook, 48, and members of her family, fit many of these characteristics to a tee. Of Norwegian decent, Cook has blond hair, green eyes and fair skin, and can remember spending a lot of her childhood at a summer cabin being “fried” by the sun. Although she lives in Minnesota, she was still frequently exposed to UV radiation while she worked at a tanning salon in college. While on a vacation in Mexico in 2009, Cook’s mother questioned the suspicious look of a mole on the right side of her back. Her primary care doctor excised the mole and subsequent biopsy tests revealed that it was a stage 1 melanoma about 0.61 mm deep.

“When I was diagnosed, I had never really heard of melanoma. I didn’t know what it was,” says Cook. “My doctor told me that it was serious, but that I was OK after this first diagnosis and just had to get regular full body checks with a dermatologist.”

Cook says she drastically changed her sun behavior and that of her family, including her teenage daughter. “I am all about sunscreen and UPF clothing and hats,” Cook says. Designed to protect against the sun, such clothing is made of fabrics that absorb or reflect UV radiation, and is rated with an Ultraviolet Protection Factor (UPF) value. Clothing with a rating of UPF 40 or greater blocks 97.5 percent of UV radiation or more. “I don’t live my life in fear," Cook continues, "but I am very careful about being outside.”

Despite that, in September 2012, Cook noticed a lump in her left breast and immediately thought that she might have breast cancer. After undergoing a mammogram, ultrasound and needle biopsy, her doctors told her that she again had melanoma. However, this time, a scan of her whole body showed that the disease was stage 4 and had spread to other parts of her body. A second melanoma at a new site is called a second primary.

“When a patient has multiple primary melanomas, we often begin to wonder about the likelihood that patient has an inherited risk for melanoma,” Schuchter says. “We are also suspicious in patients with a young age of onset, those with family members with melanoma, or patients with atypical or dysplastic nevi.”

Atypical or dysplastic nevi are unusual-looking but noncancerous moles. People who have atypical moles are at an increased risk for melanoma that can develop in the mole or elsewhere on the body. The more moles they have, the higher their risk. Certain patients may be classified as having atypical mole syndrome. These patients have 100 or more moles, one or more moles that are 8 mm or larger in diameter, or one or more moles that are atypical. Other patients may be diagnosed with familial atypical multiple mole melanoma syndrome, or FAMMM. These people have atypical mole syndrome, but also have at least one first- or second-degree relative with melanoma.

Other than these risk factors, familial melanoma presents, is staged and is treated in the same way as sporadic melanoma.

“As far as we know now, familial melanoma does not alter prognosis — just the frequency with which someone may be diagnosed,” Schuchter says.

Even when clinicians are suspicious that a melanoma is familial, they do not always conduct tests to confirm whether a patient has a genetic predisposition, according to Schuchter and Jeffrey S. Weber, M.D., Ph.D., a specialist in melanoma management and cancer immunotherapy and deputy director of the Perlmutter Cancer Center at NYU Langone Medical Center.

“If someone has already had multiple melanomas and they are already undergoing intense melanoma screening or treatment, how does knowing that they have a genetic mutation help?” Weber asks. “Knowing does not change how melanoma is treated and it does not change the advice that is given to prevent future skin cancers.” Anyone diagnosed with melanoma should already be advised to practice sun-safe behaviors and to encourage these behaviors in members of their families.

However, Funchain encourages genetic testing in these patients.

“Although inherited melanoma is not typically very different from sporadic melanoma, the more important thing about identifying inherited melanoma is the ability to look for genes that may increase the risk for other cancers,” Funchain says. “By knowing what specific mutation a patient has, we have the opportunity to narrow down and more effectively address any risk for other cancers, and, potentially, save lives.”

For two decades, two genes have been linked to familial melanoma: CDKN2A and CDK4. Factors associated with an increased likelihood of having a CDKN2A mutation include an increased number of people with melanoma within a family, melanoma diagnosis at an early age and family members with multiple primary melanomas or pancreatic cancer. A study looked for these four features in 385 families in Australia, North America and Europe that included three or more people with melanoma. Researchers found that 39 percent of these families had CDKN2A mutations.

No drugs that target these mutations have been approved for the treatment of melanoma, but Ibrance (palbociclib) — which has been approved to target these genomic glitches in advanced breast cancer &mdash; is being tested in clinical trials.

After receiving her second primary melanoma diagnosis in 2012, Cook dug into the medical history of her family, including her deceased father. She found that, although it did not cause his death, her father had been diagnosed with melanoma earlier in his life.

To treat her stage 4 melanoma, Cook underwent a series of surgeries to remove metastases, began treatment with an immunotherapy drug called Yervoy (ipilimumab) and underwent Gamma Knife radiation. She also underwent testing for the CDKN2A mutation, but the tests were negative. During her recovery, her younger brother, a typically sun-safe athlete who lived in Arizona for much of his life, visited her to help. While visiting, he revealed to her that he felt a lump in his armpit, and she encouraged him to have it immediately checked out.

“He saw several physicians who said he was likely just sick and told him not to worry about it,” Cook says. “By a fourth visit to a surgical oncologist in April 2014, my brother was diagnosed with stage 4 melanoma.”

Yervoy, which worked to shrink Cook’s tumors, did not work for her brother, and he died from melanoma three days short of his 45th birthday.

Despite the fact that Cook was negative for the CDKN2A mutation, she may still have a germline mutation that makes her more susceptible to melanoma, according to Funchain. Alterations in CDKN2A and CDK4 account for only a small percentage of familial melanomas, and other genes involved are yet to be discovered.

“At the time when Cook was tested, the first papers on screening for CDKN2A had only just been published,” Funchain says. Since then, research has revealed a multitude of other genes that may increase the risk for familial melanoma, and new gene sequencing technology has made it cheaper and easier to test for multiple genetic mutations at the same time.

In Britton’s case, her diagnosis of melanoma and her family history of ovarian cancer led her physicians to suspect that she might have mutations in the BRCA genes.

One small study followed a group of 2,729 women with BRCA1 or BRCA2 mutations for an average of five years and found that women with the BRCA2 mutation had an 83 percent increased risk for developing skin cancer compared with women with a BRCA1 mutation.

Although Britton’s melanoma diagnosis was eventually downgraded to dysplastic nevus, her genetic testing showed that she was indeed positive for BRCA1, and she underwent a prophylactic bilateral mastectomy to lower her chances of getting breast cancer later in life. Her sister underwent genetic testing for BRCA mutations, as well.

Research is slowly emerging about other gene mutations associated with familial melanoma, including BAP1, MITF, POT1 and others. Each of these genes may also be associated with increased risk for other cancers. For example, mutated BAP1 has also been linked with a higher risk for mesothelioma and ocular melanoma.

According to Funchain, the most important thing that anyone can do if they may be predisposed to familial melanoma is connect with a genetic specialist or genetic counselor.

“Hereditary genetics is not a topic that many practitioners are fully versed in, so it is an important step to get hooked up with a genetic counselor,” Funchain says. “If you see someone who knows genetics really well, they can tell the patient about what other cancers might be involved with each mutation and can send them to the right people to be screened.”

Patients can also turn to organizations such as FORCE — Facing Our Risk of Cancer Empowered &mdash; a national non-profit organization that works to create awareness around and advocate for research to support people dealing with hereditary breast, ovarian and related cancers.

For Britton, knowledge about her BRCA mutation was able to inform her sister’s decision to get screened, and, if she has children in the future, will inform theirs as well. She also keeps a close watch on her skin and continues her regular visits to a dermatologist.

Cook has now gone almost three years without evidence of disease and is living a full and fulfilling life, she says. Although her screening for the CDKN2A mutation was negative, her experience has factored into her daughter’s decision-making when it comes to sun safety and skin cancer prevention.

Overall, for melanoma prevention, the advice is the same for someone with or without familial melanoma, according to Weber.

“Stay the heck out of the sun and see a dermatologist every six months,” he says.

A tiny fraction of melanoma is inherited.

A Rare Breed: Inherited Melanoma

The risk of some kind of complication after a cystectomy and urinary diversion procedure is about 60 percent, estimates urologic oncologist Marc Smaldone, M.D., of Fox Chase Cancer Center in Philadelphia. Some studies have estimated that as many as one in four patients will require readmission to the hospital within 90 days of undergoing the procedure. In addition to physical issues, people can get depressed after urinary diversion procedures.

“We see that quite often,” Smaldone says. “In a typical survivorship plan, assessing how a patient is dealing emotionally is considered one of the most important parts of follow-up.”

One of the difficult emotional issues some people must deal with after cystectomy is the sexual side effects that often occur as a result of the procedure.

“We remove key organs for sexual function, because we want to make sure we do not leave any cancer behind,”says urologic surgeon Khurshid Guru, M.D., of Roswell Park Cancer Institute, in New York. “Patients must be educated about these sexual side effects and have their expectations managed.”

In some older men with limited sexual function, these side effects may not be as much of a concern, he adds. When patients have limited sexual function prior to the procedure, Guru tries to offer them options before the surgery to help them adapt to new techniques before they face the additional stress of surgical recovery and urinary diversion. These techniques could include the use of medications like Viagra or Cialis, or devices like a vacuum pump. For younger men, there are surgical methods that can be used to preserve the nerves that help them get and maintain an erection. Men continue to produce sperm after cystectomy, and those who want to father children may be able to do so with assistance from a fertility specialist.

In women who wish to remain sexually active, the surgeon may try to reconstruct the vagina in a way that is still functional afterwards, Smaldone says. In women who are premenopausal, Guru will often try to save the ovaries, but if the disease is too aggressive, it may not be possible.

Experts in the creation and care of stomas or neobladders after cystectomy say that it’s important for patients and their caregivers to prepare for this physical change in advance, by speaking with others who’ve been through such procedures and consulting other educational resources.

Here are a few places you can look for that guidance:

• The University of Rochester Medical Center’s Urology Department offers a 

• The American Cancer Society offers its own 

explaining bladder cancer, its causes, diagnosis and treatments, at: http://tinyurl.com/nkgkuho

• The Bladder Cancer Advocacy Network has partnered with Inspire.com to offer an 

, as well as a stateby- state list of face-to-face support groups. 

 a survivor of bladder cancer who has walked in your shoes and can give you personal counsel. 

Treating bladder cancer with a cystectomy may bring about some complicated side effects. Here are some resources to help.

Cystectomy to Treat Bladder Cancer: It's Complicated

“Life has its challenges, and this has certainly been one of them, but it has not been devastating. Life goes on.” - William O’Brien, patient [PHOTO BY JULIE BERTONAZZI]

When William O’Brien was diagnosed with bladder cancer at 75, he fit the profile of the average patient with the disease.

But for O’Brien, the day he showed his first symptom, and life since that day, has been anything but average. At the time, he and his wife, Jackie, belonged to a breakfast club that met every week on Wednesdays.

“I was at breakfast and had to go to the men’s room, and instead of urine, pure blood came out,” O’Brien recalls. “That was the first sign that there was anything wrong with me.”

O’Brien made an appointment to see his local urologist in what would be the first step of many toward ultimately undergoing a radical cystectomy to remove his bladder and learning to live life with a neobladder, a new bladder made of intestine.

Adjusting to life after his cystectomy has not been as bad as he anticipated, O’Brien says, mostly because his surgical team, led by urologic oncologist Marc Smaldone, M.D., at Fox Chase Cancer Center in Philadelphia, was very helpful in preparing him and explaining what to expect.

Bladder cancer will be diagnosed in more than 76,000 people in 2016, with an estimated 16,000 deaths. The most common type of bladder cancer is transitional cell carcinoma — or urothelial carcinoma &mdash; which starts in the cells inside of the bladder. How invasive a bladder cancer is refers to how deeply it has traveled into the bladder wall. About 70 percent of patients are diagnosed with non—muscle-invasive bladder cancer and can be treated with surgery to remove just the tumor. However, about 30 percent of bladder cancers are considered muscle-invasive, where the tumor has invaded the muscle lining the bladder, and usually require surgery to remove the bladder and some surrounding organs, called cystectomy. Although partial cystectomy is performed in select patients, leaving enough bladder to hold urine, most patients will undergo a complete cystectomy.

 “If someone is told that they have muscle-invasive disease and that they need cystectomy, they should speak with their doctor or surgeon about the possibility of receiving neoadjuvant, or pre-surgical, chemotherapy,” says urologic surgeon Khurshid Guru, M.D., of Roswell Park Cancer Institute.

The five-year survival rate after cystectomy is about 65 percent. However, a 2003 study showed that receiving chemotherapy prior to cystectomy improves survival among patients with locally advanced disease.

During the procedure, men will have the bladder, nearby pelvic lymph nodes, prostate, seminal vesicles and part of the vas deferens removed, explains Smaldone. In women, the bladder, fallopian tubes, uterus, cervix and upper one-third of the vagina are removed.

Prior to surgery, the patient and physician should discuss options for redirecting urine, or urinary diversion, once the bladder is removed.

“It is only natural that when you remove the bladder you have to divert the urine and remove it from the body,” Guru says.

The easiest and most common urinary diversion is the ileal conduit, according to Guru. In this procedure, the surgeon takes a small section of the ileum, or the small intestine, and attaches it to an opening made in the skin of the abdomen, creating what is known as a stoma. A bag is affixed to the stoma, worn externally and used to collect urine.

Another urinary diversion option is the use of an internal storage pouch for urine, sometimes called an Indiana pouch. Here the surgeon creates a sphere or pouch inside the abdomen using a combination of small and large intestine. The surgeon connects the pouch to the skin in the abdomen and a stoma is created. An Indiana pouch does not use an external pouch to collect the urine; instead, patients must learn to drain the internal pouch periodically by inserting a catheter through the stoma.

The third urinary diversion option is the creation of a neobladder. To create this new bladder, the surgeon will use part of the small intestine to create a sphere to serve as the bladder. This sphere is connected to the urethra, through which the patient can pass urine out of the body.

Smaldone estimates that about 85 percent of patients who undergo cystectomy will have an ileal conduit procedure.

“The other procedures are less common for a variety of reasons,” Smaldone says. “With any continent diversion, the patient will have to be physically able and willing to catheterize, and for either technique creating an internal reservoir, the patient has to tolerate a longer operation, have good kidney function and be willing to have a longer hospital stay and a more difficult recovery.”

“I encourage all patients to talk to other patients who have received all these types of diversion to help give them a feel of what it will be like,” Guru says. “All types of diversions have pros and cons.”

People living with a stoma and an external bag often have difficulty with body image issues, Smaldone explains. The bag may leak or have odors, and the urine could back up into the kidney, leading to infection. People who have an Indiana pouch procedure must learn how to catheterize the stoma at regular intervals. They can experience leakage of urine or irritated skin at the stoma site. Neobladder procedures require patients to learn to sense when the intestinal pouch is full because the nerves that once sent that message to the brain have been removed.

“Patients with a neobladder may experience leakage, especially at night, and it may take time to learn to empty the bladder efficiently,” Smaldone says.

When he was released from the hospital after his cystectomy procedure, O’Brien admits that it took him some time to adjust to his neobladder.

“I had to wear Depends all the time, because I was not always sure what was going on with the neobladder,” O’Brien says. “But, over time, I learned to recognize when the bladder was full and had to be emptied. The only times I lose control now are when I am not in a position to empty out or if I get to laughing too hard.”

Caregivers play an important role in helping patients adjust to life after cystectomy. Smaldone encourages caregivers to be as supportive as possible and to immerse themselves in the education process during the preoperative and hospitalization stages.

“You have to be as hands-on as possible,” Smaldone says. “When the patient goes home, that is when the real work begins.”

Caregivers may have to help patients adjust to using their urinary diversion. Often, visiting nurses will help patients adjust to using a stoma or catheterizing a pouch in the weeks immediately after surgery. During this time, caregivers should learn as much as they can.

Caregivers should also be on the lookout for complications related to the stoma or neobladder.

“Most problems have symptoms that are not so subtle,” Smaldone says.

These symptoms may include problems with leakage or skin excoriation around the stoma site, or something more serious such as a urinary tract infection or fever, another potential indication of infection. Patients need to stay hydrated immediately after the procedure, drinking about two to three liters a day, Guru says.

“One of the biggest risk factors for pelvic operations is developing a blood clot, which can debilitate or kill a patient,” Guru says. “It is important that caregivers help to ambulate the patient — keep them moving.”

O’Brien says that he cannot put into words how helpful his wife Jackie has been to him throughout this experience. Jackie says her advice to other caregivers is to remember to hang in there.

“Things get easier,” she adds. “Just knowing that you are a help to the patient is so rewarding.”

Although there was definitely an adjustment period, Jackie says it was not nearly as bad as she anticipated.

“I will tell you why,” Jackie says. “Our doctors were so helpful explaining everything.”

 reviewed several clinical trials comparing health-related quality of life for different urinary diversion options among patients who underwent radical cystectomy for bladder cancer. The study showed that no one method produced better quality-of-life outcomes, but that better quality of life was related to patient education and consideration of each patient’s individual situation.

“The education piece preoperatively is the hardest part,” he says. “Timely treatment results in better survival outcomes for bladder cancer. Since treatment decisions get made very quickly, a tremendous amount of new information gets thrown at patients in a short period of time, and it is very easy to get overwhelmed.”

To be better prepared for the possible challenges ahead, Smaldone and Guru encourage patients to talk to as many people as possible who have been through the procedure.

“These are complex procedures, and we have to make sure that patients and their loved ones have a good understanding of the expected short- and long-term recovery process before they reach the operating room,” Smaldone says.

That is exactly what William and Jackie O’Brien did, and they say they have handled the adjustment to life with a neobladder very well.

“Life has its challenges, and this has certainly been one of them, but it has not been devastating,” O’Brien says. “Jackie and I still have a very active social life. Just this morning we went to our breakfast club again. Life goes on.”

After the bladder is surgically removed and the urinary system diverted, most can return to their usual activities.

Leah K. Lawrence

Finding New Targets for Small Cell Lung Cancer

A Rare Breed: Inherited Melanoma

Cystectomy to Treat Bladder Cancer: It's Complicated

Creating a Diversion: Life After Cystectomy for Bladder Cancer

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