When Is Brachytherapy Alone The Right Choice
For some patients with disease that is confined to the prostate and not too aggressive , brachytherapy alone is a good option. It is also convenient for the patient as it is done in an outpatient setting and most people can get back to work within a few days.
But brachytherapy is not right for everyone. For some patients with less-aggressive disease, a watch-and-wait approach would be preferred. At MSK, our philosophy is that when the disease is caught very early, it is very appropriate to do active surveillance and hold off on treatment.
This philosophy applies to patients with a low PSA level, or nonaggressive disease as reflected by a Gleason score of 6 with evidence of cancer in only a few of the biopsy samples and no evidence from the MRI of a significant amount of disease. There are also very select patients with Gleason 7 disease who may be candidates for active surveillance.
Study Population And Characteristics
During the study period, 373 patients diagnosed with IR prostate cancer were treated in the Radiation Oncology Department of the CSMC 196 patients were treated with RT with concomitant short-term ADT, and 177 patients with RT alone. Table shows population and treatment-related characteristics of patients treated with RT and short-term ADT and RT alone. Patients in both arms were similar in terms of mean age at time of therapy, Gleason score at biopsy, fiducials implants, RT treatment modality , and the Charlson comorbidity score. The mean follow-up time was 55.9±37.2months and did not significantly differed between the two treatment groups. However, compared to patients treated with RT alone, patients treated with a combination of RT+ ADT had significantly more unfavorable risk factors including: higher PSA levels before RT treatment, more intermediate-risk risk factors, and a higher percent of positive cores on biopsy. Moreover, patients receiving RT and ADT had higher T-stage, however the difference did not reach statistical significance . The vast majority of patients in both groups did not receive pelvic lymph node RT , and a higher fraction of patients receiving RT and ADT were administered pelvic lymph node RT.
Table 1 Patient characteristics and treatment
Evidence For Combining Hormone Therapy And Radiation Treatment
Bolla M, Collette L, Blank L, et al. Long-Term Results with Immediate Androgen Suppression and External Irradiation in Patients with Locally Advanced Prostate Cancer : A Phase III Randomised Trial. Lancet 2002 360:1036. PMID: 12126818.
Bolla M, Gonzalez D, Warde P, et al. Improved Survival in Patients with Locally Advanced Prostate Cancer Treated with Radiotherapy and Goserelin. New England Journal of Medicine 1997 337:295300. PMID: 9233866.
DAmico AV, Schultz D, Loffredo M, et al. Biochemical Outcome Following External Beam Radiation Therapy With or Without Androgen Suppression Therapy for Clinically Localized Prostate Cancer. Journal of the American Medical Association 2000 284:12803. PMID: 10979115.
DAmico AV, Manola J, Loffredo M, et al. Six-Month Androgen Suppression Plus Radiation Therapy Versus Radiation Therapy Alone for Patients with Clinically Localized Prostate Cancer: A Randomized Controlled Trial. Journal of the American Medical Association 2004 292:8217. PMID: 15315996.
Denham JW, Steigler A, Lamb DS, et al. Short-Term Androgen Deprivation and Radiotherapy for Locally Advanced Prostate Cancer: Results from the Trans-Tasman Radiation Oncology Group 96.01 Randomised Controlled Trial. Lancet Oncology 2005 6:84150. PMID: 16257791.
Nesslinger NJ, Sahota RA, Stone B, et al. Standard Treatments Induce Antigen-Specific Immune Responses in Prostate Cancer. Clinical Cancer Research 2007 13:1493502. PMID: 17332294.
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Radiopharmaceuticals That Target Psma
Prostate-specific membrane antigen is a protein that is often found in large amounts on prostate cancer cells.
Lutetium Lu 177 vipivotide tetraxetan is a radiopharmaceutical that attaches to PSMA, bringing radiation directly to the prostate cancer cells.
This drug can be used to treat prostate cancer that has spread and that has already been treated with hormone therapy and chemotherapy. The cancer cells must also have the PSMA protein. Your doctor will order a PSMA PET scan before you get this drug to make sure the cancer cells have PSMA.
This drug is given as an injection or infusion into a vein , typically once every 6 weeks for up to 6 doses.
Possible side effects
Some of the more common side effects of this drug include:
- Feeling tired
This drug can lower blood cell counts:
- A low red blood cell count can cause tiredness, weakness, pale skin, or shortness of breath.
- A low blood platelet count can lead to bleeding or bruising more easily than normal, or bleeding that is hard to stop.
- A low white blood cell count can lead to an increased risk of infections, which might show as a fever, chills, sore throat, or mouth sores.
This drug might damage the kidneys. Your doctor or nurse will likely advise you to drink plenty of fluids and to urinate often before and after getting this drug, to help protect the kidneys. Tell your doctor or nurse if you start to pass less urine than is normal for you.
Mutational And Genetic Testing In Mcrpc
All cancers, including prostate cancer, arise because of genetic mutations in cells. The first type mutations to be appreciated as causative in driving mCRPC were in genes involved in repair of damaged DNA. These mutations, often hereditary, were identified long ago as predisposing to the development of breast and ovarian cancers in women.
In prostate cancer, mutations in one of these DNA-repair genes are found mostly in late-stage prostate cancer in about 12% to 20% of patients. These mutations predict whether treatment with drugs known as PARP inhibitors might be effective. The FDA has already approved two drugs in this category: olaparib and rucaparib . New clinical guidelines now dictate testing for these mutations in tumors of mCRCP patients.
A recent study reported that men with deficiencies in one of 13 genes related to DNA damage repair had a higher response rate and a longer progression-free and overall survival when treated with the PARP inhibitor olaparib versus an anti-androgen treatment.
A new drug called berzosertib, an inhibitor of the DNA-repair protein ATR, has shown very promising results in a variety of cancers with relevant mutations, and is currently being tested in a trial for mCRPC in combination with chemotherapy.
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Quality Of Life With Mcrpc
According to a review published in the British Medical Journal in October 2016, you may not experience pain or other symptoms at this stage of cancer, or you may experience many. Its different for everyone. So along with treating the cancer itself, be sure to talk to your doctors about any symptoms and side effects youre experiencing in order so that the right ways to alleviate them can be found. You should also ask your care team about options for palliative care.
Because it can be very stressful to have advanced prostate cancer, and tough to talk about what it all means for your future, the ASCO urges men to have an open and honest conversation with their care team. Discuss what youre worried about, and whats important to you. There are many ways to look for and get emotional support.
Additional reporting by Andrea Peirce
What Types Of Hormone Therapy Are Used For Prostate Cancer
- reducing androgen production by the testicles
- blocking the action of androgens throughout the body
- block androgen production throughout the body
Treatments that reduce androgen production by the testicles are the most commonly used hormone therapies for prostate cancer and the first type of hormone therapy that most men with prostate cancer receive. This form of hormone therapy includes:
Treatments that block the action of androgens in the body are typically used when ADT stops working. Such treatments include:
Treatments that block the production of androgens throughout the body include:
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Intensity Modulated Radiation Therapy
IMRT, an advanced form of 3D-CRT therapy, is the most common type of external beam radiation therapy for prostate cancer. It uses a computer-driven machine that moves around the patient as it delivers radiation. Along with shaping the beams and aiming them at the prostate from several angles, the intensity of the beams can be adjusted to limit the doses of radiation reaching nearby normal tissues. This lets doctors deliver an even higher radiation dose to the cancer.
Some newer radiation machines have imaging scanners built into them. This advance, known as image guided radiation therapy , lets the doctor take pictures of the prostate just before giving the radiation to make minor adjustments in aiming. This appears to help deliver the radiation even more precisely and results in fewer side effects.
A variation of IMRT is called volumetric modulated arc therapy . It uses a machine that delivers radiation quickly as it rotates once around the body. This allows each treatment to be given over just a few minutes. Although this can be more convenient for the patient, it hasnt yet been shown to be more effective than regular IMRT.
How Does Hormone Therapy Work
Hormone therapy for prostate cancer works by either preventing the body from making these androgens or by blocking their effects. Either way, the hormone levels drop, and the cancer’s growth slows.
“Testosterone and other hormones are like fertilizer for cancer cells,” Holden tells WebMD. “If you take them away, the cancer goes into shock, and some of the cells die.”
In 85% to 90% of cases of advanced prostate cancer, hormone therapy can shrink the tumor.
However, hormone therapy for prostate cancer doesn’t work forever. The problem is that not all cancer cells need hormones to grow. Over time, these cells that aren’t reliant on hormones will spread. If this happens, hormone therapy won’t help anymore, and your doctor will need to shift to a different treatment approach.
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What Is Stereotactic Body Radiation Therapy And What Advantages Does It Offer
Stereotactic body radiation therapy, or SBRT, involves the use of sophisticated image guidance that pinpoints the exact three-dimensional location of a tumor so the radiation can be more precisely delivered to cancer cells. Traditionally, external beam radiation has been delivered in anywhere from 45-48 sessions over multiple weeks. But large, randomized studies have shown that shorter courses of radiation are just as safe and effective. Therefore, at MSK, we have shortened all our radiation courses.
There is increasing interest in giving this radiation in very short courses of treatment using intense radiation doses, called hypofractionated radiation therapy. Many of the people we care for have a type of radiation therapy called MSK PreciseTM. This is a hypofractionated form of SBRT that can be given in five sessions. MSK has been doing this for the past 20 years, and the results in the several hundred people whove been treated have been excellent so far. The treatment is very well tolerated and quite effective
Because of its superior precision, MSK Precise can have fewer side effects than more conventional radiation techniques, with extremely low rates of incontinence and rectal problems. The sexual side effects are low, similar to what is experienced with more extended external radiation techniques. And of course, its much more convenient for patients.
Hormone Treatment Fights Prostate Cancer
Hormone therapy for prostate cancer has come a long way in the past few decades. Not so long ago, the only hormonal treatment for this disease was drastic: an orchiectomy, the surgical removal of the testicles.
Now we have a number of medications — available as pills, injections, and implants — that can give men the benefits of decreasing male hormone levels without irreversible surgery.
“I think hormonal therapy has done wonders for men with prostate cancer,” Stuart Holden, MD, Medical Director of the Prostate Cancer Foundation.
Hormone therapy for prostate cancer does have limitations. Right now, it’s usually used only in men whose cancer has recurred or spread elsewhere in the body.
But even in cases where removing or killing the cancer isn’t possible, hormone therapy can help slow down cancer growth. Though it isn’t a cure, hormone therapy for prostate cancer can help men with prostate cancer feel better and add years to their lives.
On average, hormone therapy can stop the advance of cancer for two to three years. However, it varies from case to case. Some men do well on hormone therapy for much longer.
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Table : Boosting The Effectiveness Of Radiation Therapy
A randomized controlled study involving 206 men with early-stage prostate cancer evaluated whether adding six months of hormone therapy to external-beam radiation treatment would boost both overall survival and disease-free survival . The results are given below. The same research group found, in an earlier study, that the addition of hormone therapy was of most benefit to men who were considered at moderate or high risk, based on their clinical profile.
Five-year follow-up 82% Source: Journal of the American Medical Association, 2004 292:8217. PMID: 15315996.
Combined with radiation therapy. A number of studies have shown that men with early-stage prostate cancer are more likely to be cured when hormone therapy is given in conjunction with radiation therapy . Even when the disease is regionally advanced, meaning that it has progressed to tissues immediately surrounding the prostate gland, neoadjuvant hormone therapy reduces risk of progression and relapse .
Treatment To Lower Androgen Levels From The Adrenal Glands
LHRH agonists and antagonists can stop the testicles from making androgens, but cells in other parts of the body, such as the adrenal glands, and prostate cancer cells themselves, can still make male hormones, which can fuel cancer growth. Some drugs can block the formation of androgens made by these cells.
Abiraterone blocks an enzyme called CYP17, which helps stop these cells from making androgens.
Abiraterone can be used in men with advanced prostate cancer that is either:
- High risk
This drug is taken as pills every day. It doesnt stop the testicles from making testosterone, so men who havent had an orchiectomy need to continue treatment with an LHRH agonist or antagonist. Because abiraterone also lowers the level of some other hormones in the body, prednisone needs to be taken during treatment as well to avoid certain side effects.
Ketoconazole , first used for treating fungal infections, also blocks production of androgens made in the adrenal glands, much like abiraterone. It’s most often used to treat men just diagnosed with advanced prostate cancer who have a lot of cancer in the body, as it offers a quick way to lower testosterone levels. It can also be tried if other forms of hormone therapy are no longer working.
Ketoconazole also can block the production of cortisol, an important steroid hormone in the body, so men treated with this drug often need to take a corticosteroid .
Are There Side Effects Of The Combination Approach
There is a slightly higher chance that patients who receive the combined therapy will have rectal irritation or urinary side effects. This is common with prostate cancer radiation therapy because the radiation can damage cells in the tissues surrounding the prostate. But at MSK, we routinely use sophisticated computer-based planning techniques that help us reduce the dose given to normal tissues such as the rectum, bladder, and urethra, lessening the chances of side effects and complications. We have also found that, when treating with the combined approach, using the high-dose-rate brachytherapy compared to low-dose-rate brachytherapy may have less in the way of side effects.
In addition, at MSK, we routinely use a rectal spacer gel, which we inject between the prostate and the rectum while the patient is under mild anesthesia, to create a buffer between these two tissues. By creating this space, we can further reduce the dose of radiation the rectum is exposed to. This leads to fewer side effects for the patient. The rectal spacer gel is biodegradable and dissolves on its own within the body after a few months.
Definitions That May Help
Your doctor may use specific terms to let you know how your cancer is responding to hormone therapy or other treatments. They include:
- Castrate level: When the testicles are removed and testosterone levels plummet, this is referred to as the castrate level. Androgen levels that remain this low are most beneficial for reducing the impact of prostate cancer. Hormone therapy is designed to keep testosterone at castrate level.
- Castrate-sensitive prostate cancer : CSPC refers to prostate cancer that is being controlled successfully with testosterone at castrate level.
- Castrate-resistant prostate cancer : CRPC prostate cancer refers to cancer that is not successfully controlled, even though testosterone levels are at or below castrate level. CRPC may require additional medications, such as a CYP-17 inhibitor or one of the newer antiandrogens.
- Hormone-refractory prostate cancer : HRPC is prostate cancer that is no longer responsive to any type of hormone therapy, including newer medications.
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Symptomatic treatment of an enlarged prostate usually involves a combination of medication and lifestyle changes. A diet rich in fruits and vegetables may be the best option if you suffer from chronic urination. It will help the body adjust to the increased size of the prostate. Also, taking regular urination intervals will help retrain the bladder to function properly. Inactivity also contributes to urine retention, and cold temperatures can increase the urge to urinate.
Invasive treatment of enlarged prostate includes medication that relieves the pressure on the urethra and bladder. However, if the condition is severe, it may require surgical intervention. If treatment is not successful, the enlarged prostate can become a potentially life-threatening disease. As the hormone levels in the body change, the enlarged prostate can lead to various complications, including urinary retention and even cancer. This is why it is critical to see a doctor for further evaluation.
A physician can recommend a number of treatments to address an enlarged prostate. An enlarged prostate will require surgery to relieve the symptoms. In most cases, surgical treatment for an enlargement of the penis is enough. Moreover, a doctor may recommend a course of treatment based on symptoms. A TURP procedure is not painful and requires less recovery time than open surgery. The recovery period will be shorter and less traumatic.