Treating Bladder Cancer That Progresses Or Recurs
If cancer continues to grow during treatment or comes back after treatment , treatment options will depend on where and how much the cancer has spread, what treatments have already been used, and the patient’s overall health and desire for more treatment. Its important to understand the goal of any further treatment if its to try to cure the cancer, to slow its growth, or to help relieve symptoms as well as the likely benefits and risks.
For instance, non-invasive bladder cancer often comes back in the bladder. The new cancer may be found either in the same place as the original cancer or in other parts of the bladder. These tumors are often treated the same way as the first tumor. But if the cancer keeps coming back, a cystectomy may be needed. For some non-invasive tumors that keep growing even with BCG treatment, and where a cystectomy is not an option, immunotherapy with pembrolizumab might be recommended.
Cancers that recur in distant parts of the body can be harder to remove with surgery, so other treatments, such as chemotherapy, immunotherapy, targeted therapy, or radiation therapy, might be needed. For more on dealing with a recurrence, see Understanding Recurrence.
Tumor Mutational Burden/neoantigen Burden
Fig. 2
Tumor mutation burden as a biomarker for anti-PD-1/PD-L1 therapy. a Kaplan-Meier estimate of overall survival according to estimated mutational burden by quartiles in mUC patients treated with atezolizumab in IMVigor 210 Cohort I. Range estimates next to each qauartile indicated number of mutations per megabase for each quartile. b Quantification of mutation burden across TCGA subtypes and PD-L1 immune cell IHC status and correlation with disease status. c and d Progression-free survival based on tertile of tumor mutation burden from Checkmate 026, a randomized study of nivolumab compared to standard of care chemotherapy . A and B reprinted from The Lancet, Vol. 389, Balar et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicenter, phase 2 trial, p. 73, 2017 with permission from Elsevier . C and D reproduced with permission from Carbone, D. et al. NEJM. 2017.,
Intermediate Risk Early Bladder Cancer
People with intermediate-risk non-muscle-invasive bladder cancer should be offered a course of at least 6 doses of chemotherapy. The liquid is placed directly into your bladder, using a catheter, and kept there for around an hour before being drained away.
You should be offered follow-up appointments at 3, 9 and 18 months, then once every year. At these appointments, your bladder will be checked using a cystoscopy. If your cancer returns within 5 years, you’ll be referred back to a specialist urology team.
Some of the chemotherapy medicine may be left in your urine after treatment, which could severely irritate your skin.
It helps if you sit down to urinate and that you’re careful not to splash yourself or the toilet seat. Always wash the skin around your genitals with soap and water afterwards.
If you’re sexually active, it’s important to use a barrier method of contraception, such as a condom. This is because the medicines may be present in your semen or vaginal fluids, which can cause irritation.
You also shouldn’t try to get pregnant or father a child while having chemotherapy for bladder cancer, as the medicines can increase the risk of having a child with birth defects.
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How Effective Is Immunotherapy For Bladder Cancer
Bladder cancer has no cure at the present time, and the five-year survival rate is about 10 percent. One of the biggest challenges in treating bladder cancer is the lack of early detection, which means that the cancer has spread by the time it becomes symptomatic.
Because immunotherapy can be particularly effective at treating advanced, metastatic bladder cancer, the Food and Drug Administration has approved it for this purpose.
Immunotherapy Finds A Foothold In Metastatic Bladder Cancer But Frontline Challenges Remain
The emergence of checkpoint inhibitors has transformed the second-line treatment of patients with metastatic bladder cancer. However, questions regarding the utility of immunotherapy in the frontline setting remain unanswered, leaving chemotherapy as the standard-of-care option.
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The emergence of checkpoint inhibitors has transformed the second-line treatment of patients with metastatic bladder cancer . However, questions regarding the utility of immunotherapy in the frontline setting remain unanswered, leaving chemotherapy as the standard-of-care option, said Arjun V. Balar, MD.
Although atezolizumab and pembrolizumab have frontline FDA indications for patients with PD-L1positive, cisplatin-ineligible mBC, ongoing trials are evaluating immunotherapy combinations as well as emerging modalities such as antibody-drug conjugates .
Additionally, immunotherapy is being brought into muscle-invasive bladder cancer and nonMIBC, and the modality may have utility in combination with chemoradiation in MIBC.
Chemotherapy Gives Way to Checkpoint Inhibition in Second-Line mBC
Five PD-1/PD-L1 inhibitors have been FDA approved for the second-line treatment of patients with mBC, showing improved responses compared with single-agent chemotherapy.
Chemotherapy Combos Yield Underwhelming Data in the Metastatic Setting
The KEYNOTE-361 trial yielded similar findings, and the PFS results did not meet statistical significance.4
Emerging Options
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If Your Immunotherapy Stops Working
Immunotherapy may not work for everyone who takes it. If youâve tried it and it didnât stop your cancer, you still have a few options. What kind of treatment you get next depends on what others youâve tried and what stage your cancer is in.
This treatment uses powerful drugs to kill cancer. Even if youâve already tried some drugs before or along with your immunotherapy, your doctor may try other ones or different combinations of medicines to fight your cancer. Chemo drugs for the most common form of bladder cancer include:
Youâll get chemotherapy in cycles with a few weeks in between to give your body time to recover.
Surgery
If you still have all or part of your bladder, your doctor might recommend an operation called a radical cystectomy. Your doctor will take out all of your bladder and the lymph nodes nearby. They might also remove some of your reproductive organs. For men, that could be the prostate gland and seminal vesicles. For women, it might be the ovaries, fallopian tubes, uterus, cervix, and a small part of the vagina.
If you think you might want to join a clinical trial, your doctor will help you make the decision. They will talk about:
- How the new treatment is different from the usual treatments you could get
- What the risks are
- Any tests youâll need
- How often youâll get treatment
Youâll be able to leave the clinical trial whenever you want, for whatever reason you might have.
Treating Complications Of Bcg Therapy
If you do experience a problem from BCG infection, you may need to receive targeted antibiotics, such as isoniazid and rifampin.
Complications of BCG therapy sometimes dont occur until years later. That can happen if the BCG bacteria that spread in the body become reactivated. These complications can sometimes be tricky to diagnose. Medical imaging might first make your clinician concerned about cancer or about another type of bacterial infection.
Make sure that all your medical care providers know that you have had BCG therapy. That will help guide their diagnostic process and ensure you get the best possible care. In some cases, your clinician will want a tissue sample from the involved area to make sure that the problem is from a BCG infection and not from some other source.
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What Is Immunotherapy Used For
Immunotherapy is also used to treat bladder cancer that has spread to lymph nodes or the lining of your bladder, called the urethra. These cancers are called urothelial carcinomas.
Its also used to treat bladder cancer that has spread from your bladder to other areas in your body such as your kidneys, lungs, or liver.
Immunotherapy is not currently approved for treatment of early-stage bladder cancer.
Subtleties And Future Questions
Several factors have to be carefully considered in interpreting the trial results, explained Dr. Apolo.
A major one is that the study did not directly compare survival between people who got avelumab immediately versus when their cancer progressed. Only about half of the participants who initially received supportive care alone went on to receive immunotherapy after their cancer got worse. There could be many reasons for this, including lack of access to these drugs in different countries, Dr. Apolo said.
But it also might be that, for some people, the cancer was progressing too rapidly, she added. When these tumors start growing, they start growing very quickly. So if you wait to start at the time of progression, maybe its too late, added Dr. Apolo.
Not all patients will be caught by the second-line safety net, agreed Dr. Plimack.
So, for now, said Dr. Balar, the takeaway message from the JAVELIN study is after chemotherapy, dont wait to give immunotherapy.
But more and more, studies are looking at whether some patients should receive immunotherapy as first-line treatment, he continued. Immunotherapy is one of the most important advances weve made in the last 30 years, Dr. Balar said.
The JAVELIN results cant provide any insight into which patients benefit from first-line treatment with a platinum-based chemotherapy, he added. This trial wasnt designed to ask: Is chemotherapy necessarily the best choice for every patient? he explained.
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Treating Stage Iii Bladder Cancer
These cancers have reached the outside of the bladder and might have grown into nearby tissues or organs and/or lymph nodes . They have not spread to distant parts of the body.
Transurethral resection is often done first to find out how far the cancer has grown into the bladder wall. Chemotherapy followed by radical cystectomy is then the standard treatment.Partial cystectomy is rarely an option for stage III cancers.
Chemotherapy before surgery can shrink the tumor, which may make surgery easier. Chemo can also kill any cancer cells that could already have spread to other areas of the body and help people live longer. It can be especially useful for T4 tumors, which have spread outside the bladder. When chemo is given first, surgery to remove the bladder is delayed. The delay is not a problem if the chemo shrinks the cancer, but it can be harmful if it continues to grow during chemo. Sometimes the chemo shrinks the tumor enough that intravesical therapy or chemo with radiation is possible instead of surgery.
Some patients get chemo after surgery to kill any cancer cells left after surgery that are too small to see. Chemo given after cystectomy may help patients stay cancer-free longer, but so far its not clear if it helps them live longer. If cancer is found in nearby lymph nodes, radiation may be needed after surgery. Another option is chemo, but only if it wasn’t given before surgery.
Chemotherapy Plus Immunotherapy Before Surgery Is Beneficial For Invasive Bladder Cancer Outcomes
By ckalnen
A new study is the first to report the beneficial use of chemotherapy plus immunotherapy before surgical removal of the bladder in muscle-invasive bladder cancer . Researchers at the University of North Carolina Lineberger Comprehensive Cancer Center led the study, reporting that the regimen reduced the invasiveness of the cancer in 56% of patients in a phase II clinical trial.
The findings were published in the Journal of Clinical Oncology.
Downstaging, or treating tumors so that they become less invasive prior to surgical removal, is an important tool in muscle-invasive bladder cancer, said UNC Linebergers Tracy Rose, MD, MPH, assistant professor at the UNC School of Medicine and lead author of this finding. If we can treat a tumor pre-surgically so that it regresses to a stage where it is superficial and does not invade the bladder muscle wall, the chances of long-term survival are better.
Nearly 25% of all bladder cancers are muscle invasive. Surgical removal of the bladder is performed in many MIBC cases, but often microscopic cancer cells have already spread to lymph nodes, greatly reducing chances of a cure. In these cases, clinicians often use cisplatin chemotherapy before removal of the bladder to reduce tumor volume and kill micro-metastases. Despite this aggressive treatment, more than half of patients see their cancer return within two years.
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Starting Immunotherapy: What To Expect
The FDA has approved several immunotherapy drugs to treat bladder cancer:
Once you and your doctor decide to start one of these treatments, it helps to know a bit about what you can expect while youâre getting it.
How do you get immunotherapy?
To get immunotherapy, youâll go to a treatment center on a regular schedule to get the medicine through an infusion, a tube that goes into a vein. Your doctor will decide how many rounds of treatment you need.
Your doctor will order some lab tests before and during your treatment to see how your body responds to the drug.
You take the medicine through a tube that goes in one of your veins.
A doctor or nurse will look after you when youâre getting the IV to make sure you donât have any bad reactions or side effects. If you do, your doctor might slow down the infusion or delay or stop the treatment.
Speak up if you feel any of these while youâre getting treatment:
- Flushing
- Chills
- Confusion
- Rash
Some immunotherapy drugs can also affect your ability to have children. Talk to your doctor before you start treatment to figure out the options you have if you want to have a baby in the future.
What Is The Immune System And How Does It Work With Cancer
The immune system is a natural part of our body. Its role is to get rid of foreign or damaged material and cells before they cause trouble.
Most of the time, our immune system can find foreign invaders like bacteria and viruses, and destroy them. The immune system uses signals to attack them while leaving healthy cells alone.
Cancer is different from an illness caused by a bacteria or virus. It involves the uncontrolled growth of normal body cells. In other words, cancer cells may not be found by the immune system. Though they look different under the microscope, cancer cells can hide and grow. One way cancer cells hide is to express proteins on their surface to turn-on a “checkpoint” to stop an immune system attack.
The National Cancer Institute studied common tumors in its Cancer Genome Atlas project. The research showed that bladder cancer, skin cancer and lung cancer have the most cellular changes . These types of cancer may be more likely to respond to treatments that help the immune system find cancer cells, called “immunotherapies”.
What is Immunotherapy?
Immunotherapy is any treatment that makes the immune system stronger. For cancer, it helps the body find and attack cancer cells. The field of immuno-oncology studies how the immune system interacts with cancer. It uses that information to make new treatments.
What Happens Under Normal Conditions?
What Happens When Cancer Cells Grow and Hide?
Three things help cancers hide from the immune system:
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What Are Immunotherapy And Chemotherapy
Both types of treatments target tumor cells, but they use different methods. Immunotherapy acts on your immune system, while chemotherapy acts on the cancer cells growing inside you.
Cancer immunotherapies work in several different ways to alert and train a person’s immune system to identify and destroy cancer cells. It does this by triggering a stronger than normal immune response.1
Basically, it trains the immune system to recognize cancer cells and then turns the immune system against the cancer. The idea of harnessing the human immune system to fight cancer dates back more than a century.3
Ideally, immunotherapy will produce a long-lasting population of immune cells that can seek out and eliminate cancer cells.4
Chemotherapy works differently. It is a drug that directly attacks fast-growing tumor cells by targeting all rapidly dividing cells inside a person’s body. Unfortunately, sometimes healthy cells also get destroyed in the process.1
What Happens During Treatment
A urinary catheter is inserted through your urethra and into your bladder. Then the BCG solution is injected into the catheter. The catheter is clamped off so the solution stays in your bladder. Some doctors may remove the catheter at this time.
You have to hold the medicine in your bladder. Youll be instructed to lie on your back and to roll from side to side to make sure the solution reaches your entire bladder.
After about two hours, the catheter is unclamped so the fluid can be drained. If the catheter was already removed, youll be asked to empty your bladder at this time.
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Keytruda Improves Survival Of Advanced Bladder Cancer
CancerConnect News: Patients with recurrent urothelial cancer lived longer when they received Keytruda compared to chemotherapy as second-line treatment, according to long-term follow of a clinical trial presented at the Genitourinary Cancer Symposium.1
About Bladder Cancer
Bladder cancer will be diagnosed in approximately 77,000 people in the United States this year alone. The average age that patients are diagnosed with bladder cancer is 70 years, with 80% of these patients being former smokers. The most common type of bladder cancer is urothelial carcinoma, whereby cancer begins in the cells that line the bladder.
Urothelial carcinoma may involve parts of the kidney, bladder, and ureter . Urothelial carcinomas begin in the cells that line the particular organ in which the cancer develops. If detected and treated early, cure rates are high. However, once bladder cancer has spread outside of the bladder to distant sites in the body, effective treatment options remain limited, particularly if a patient experiences a cancer recurrence following prior therapies. Advanced bladder cancer refers to cancer that has spread outside the bladder to regional or distant sites in the body.
About Keytruda
About The KEYNOTE-045 Clinical Study
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