Monday, September 26, 2022

Hormone Shot Prior To Prostate Radiation

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A New Treatment Standard

Intermittent Hormone Therapy for Prostate Cancer 101 | Ask a Prostate Expert, Mark Scholz, MD

Still, some men have difficulty tolerating ADT, and not all of them should get it, particularly if theyre older and more likely to die of something other than prostate cancer. Id reserve ADT for younger men with a long life expectancy ahead of them who were diagnosed initially with high-grade or late-stage disease, Thompson said.

This important study confirms that combined therapy is superior to radiation alone and should be viewed as the standard treatment for PSA relapse, said Dr. Marc Garnick, the Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, and editor in chief of HarvardProstateKnowledge.org. High dose bicalutamide has been associated with cardiovascular side effects, but ongoing and future research is clarifying how best to use ADT in this particular setting.

About the Author

Charlie Schmidt, Editor, Harvard Medical School Annual Report on Prostate Diseases

Selection Of Candidates For Nadt

High-risk patients with localized prostate carcinoma are likely to benefit most from effective neoadjuvant therapy. However, heterogeneous definitions of high-risk disease render trial-to-trial comparisons difficult.

The use of preoperative nomograms that incorporate clinical T classification, serum PSA level, and biopsy Gleason grade can enhance prediction of the risk of PSA recurrence and selection of a relatively homogeneous population. The percentage of cancer in biopsy cores and the number of positive biopsy cores, as well as the incorporation of biomarkers , may further improve predictive accuracy.

Although a relatively high threshold of PSA recurrence to determine eligibility is reasonable, it may negatively affect accrual. In addition, investigators may determine that radiotherapy, instead of prostatectomy, is the optimal treatment in such high-risk patients. Conversely, setting a lower threshold of recurrence may result in unnecessary treatment, a reduction in the event rate, and an increase in the number of patients required.

It may be reasonable to hypothesize that patients with a relatively high risk of recurrence may be optimal candidates for cytotoxic chemotherapy, whereas those with a lower risk of recurrence may be optimal candidates for more tolerable biologic agents and immunotherapy.

How Will I Know That My Hormone Therapy Is Working

Doctors cannot predict how long hormone therapy will be effective in suppressing the growth of any individual mans prostate cancer. Therefore, men who take hormone therapy for more than a few months are regularly tested to determine the level of PSA in their blood. An increase in PSA level may indicate that a mans cancer has started growing again. A PSA level that continues to increase while hormone therapy is successfully keeping androgen levels extremely low is an indicator that a mans prostate cancer has become resistant to the hormone therapy that is currently being used.

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Checking Your Hormone Therapy Is Working

You have regular blood tests to check the level of a protein called prostate specific antigen . PSA is a protein made by both normal and cancerous prostate cells. It is in the blood in small amounts in all men, unless you have had the prostate gland completely removed.

While the hormone therapy is working, the level of PSA should stay stable or may go down. But if prostate cancer starts to grow and develop, the level of PSA may go up. This is hormone resistant prostate cancer or castrate resistant prostate cancer. Then your doctor may need to change your treatment. They will discuss this with you

Therapies That Interfere With Androgen Function

Side Effects From Radiation For Prostate Cancer

Taken daily as pills, antiandrogens bind to the androgen receptor proteins in the prostate cells, preventing the androgens from functioning. In addition to preventing a flare reaction, antiandrogens may be added to your treatment plan if an orchiectomy, LHRH agonist or LHRH antagonist is no longer working by itself. Commonly prescribed antiandrogens include flutamide and bicalutamide .

Enzalutamide is a newer type of antiandrogen that blocks the signal that the receptor normally sends to the cells control center to trigger growth and division. This antiandrogen may be used to treat castration-resistant prostate cancer.

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> > > This Simple Morning Test Will Fix Your Prostate

Another type of prostate issue is chronic prostatitis, or chronic pelvic pain syndrome. This condition causes pain in the lower back and groin area, and may cause urinary retention. Symptoms include leaking and discomfort. In severe cases, a catheter may be required to relieve the symptoms. If the problem is unresponsive to other treatments, your doctor may suggest a surgical procedure. If these do not work, your symptoms could progress and become chronic.

An acute bacterial infection can cause a burning sensation. Inflammation of the prostate can affect the bladder and result in discomfort and other symptoms. This is the most common urinary tract problem in men under 50, and the third most common in men over 65. The symptoms of acute bacterial prostatitis are similar to those of CPPS. Patients may experience a fever or chills as a result of the infection.

A bacterial infection can also lead to prostate issues. Acute bacterial infections can be hard to treat. Some men with a bacterial infection may need to take antibiotics to prevent or treat symptoms. Symptoms of the disease include fever and chills, pain in the lower back and the tip of the penis. Some men may have blood in the urine, frequent urination, and blood in the urine. If you suffer from acute bacterial prostatitis, a medical professional should be able to prescribe you the appropriate treatments to prevent the disease.

Vasomotor Symptoms Hot Flashes

The so-called hot flashes or, more precisely, vasomotor flushings are a common and well-described treatment toxicity in men undergoing androgen ablation and are one of the most frequently reported adverse consequences of ADT. Spetz et al performed a prospective analysis comparing the incidence of hot flashes in men receiving CAB to that in men receiving estrogen therapy for treatment of PC.52 In this study, in 915 patients with metastatic disease, 458 were treated with polyestradiol phosphate and 457 patients received CAB. Of men receiving CAB, 74.3% reported hot flashes compared to 30.1% in men receiving estrogen therapy . Further, a significantly greater percentage of men treated with CAB were greatly distressed by the hot flashes and reported at least 4 hot flashes per day . ADT-associated vasomotor flushing remains a common complaint reported by men receiving this therapy and is reported in up to 80% of men receiving ADT. Interestingly, megestrol acetate has been demonstrated to reduce hot flash symptoms by up to 85%. On the other hand, chills, weight gain, and carpal tunnel-like pain are the reported side effects of megestrol acetate.53

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Combining Nadt And Chemotherapy

Pan et al conducted a retrospective review of 3 different therapies in patients with very-high-risk localized prostate cancer: neoadjuvant chemohormonal therapy , in 60 men neoadjuvant hormonal therapy , in 73 men and immediate RP without neoadjuvant therapy , in 44 men. The NCHT group had better biochemical progression-free survival time after surgery compared with the NHT and No-NT groups . After RP, 81% of patients in NCHT group, 73% of patients in NHT group, and 48% of patients in No-NT group achieved an undetectable PSA , despite patients in the NCHT having significantly poorer prognostic factors. Randomized controlled investigations are needed to validate these results, and further follow-up is required.

Multiple phase I/II trials have also been performed to investigate the use of neoadjuvant chemotherapy alone prior to RP, however no patients in these trials achieved a complete pathologic response . As there is currently no evidence demonstrating improved clinical outcomes with the use of neoadjuvant chemotherapy alone or neoadjuvant androgen deprivation therapy alone, future research will likely focus on combined neoadjuvant chemohormonal therapy.

Although no data have yet emerged that definitively support the routine use of neoadjuvant chemohormonal therapy, its safety has been evidenced by several phase I/II clinical trials. Most of the trials on neoadjuvant chemohormonal therapy have investigated docetaxel. These are summarized in Table 4 below.

Systemic Therapy For Metastatic Disease

Hormone Therapy for Prostate Cancer

The most common use of hormone therapy today is to treat men whose prostate cancer has metastasized to other parts of the body. If prostate cancer cells escape the prostate, they migrate first to surrounding structures, such as the seminal vesicles and lymph nodes, and later to the bones or, rarely, to other soft tissues.

Hormone therapy is recommended as a palliative treatment, to relieve symptoms such as bone pain. And while hormone therapy is not a cure, in that it cant eliminate prostate cancer completely, it often extends life for many years. By reducing testosterone levels, hormone therapy can shrink a prostate tumor and its metastases and slow further progression of the cancer for so long that sometimes a man with this disease dies of something other than prostate cancer.

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Intermittent Hormonal Therapy For Locally Advanced Prostate Cancer

Intermittent hormonal therapy is where you stop taking the drugs and after a while start taking them again. This may be an option for locally-advanced prostate cancer. It gives you a break from the side effects of hormonal therapy.

Intermittent hormonal therapy is not suitable for everyone and should only be done on your doctors advice. Your doctor can explain more about this. They usually measure your PSA level using the PSA test every 3 months. If it goes up to a certain level or you get symptoms, your doctor will advise you to start hormonal therapy again.

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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Side Effects Of Hormone Therapy

As the primary male hormone, testosterone plays an important role in establishing and maintaining the typical male characteristics along with a variety of other processes in the body.

The potential effects of testosterone loss include the following:

  • Hot flashes

  • Osteoporosis, which can lead to bone fractures

  • Fatigue

Planning And Treatment Guidelines

Hormone therapy for prostate cancer increases cardiac risk

External beam RT: The prostate and proximal seminal vesicles were contoured on axial images from the treatment planning CT scan, and merged to form the clinical target volume . The CTV was expanded 1cm in 3 dimensions, except for 0.7cm posteriorly to create the planning target volume . The PTV was planned to 95% of the prescribed dose. Three treatment protocols evolved during the study time as follows: From 2001 to 2009, patients received 3D conformal RT, with a total dose of 78Gy- 82Gy at 2Gy/fraction from 2004 to 2011, patients received Intensity-Modulated RT with a total dose of 78Gy- 82Gy at 2Gy/FX and from 2010 to 2016, patients received volumetric modulated arc therapy and mild hypo-fractionation to 73.6Gy at 2.3Gy/FX .

Androgen Deprivation Therapy: all patients in the combined RT+ ADT group received two depot subcutaneous injections of Goserelin 10.8mg every 3months to a minimum of 6months effect. Bicalutamide 50mg was co-administered in the first month to prevent testosterone flare. Patients in the RT alone group did not receive any hormonal therapy during RT.

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Possible Risks And Side Effects Of Brachytherapy

Radiation precautions: If you get permanent brachytherapy, the seeds will give off small amounts of radiation for several weeks or months. Even though the radiation doesnt travel far, your doctor may advise you to stay away from pregnant women and small children during this time. If you plan on traveling, you might want to get a doctors note regarding your treatment, as low levels of radiation can sometimes be picked up by detection systems at airports.

Theres also a small risk that some of the seeds might move . You may be asked to strain your urine for the first week or so to catch any seeds that might come out. You may be asked to take other precautions as well, such as wearing a condom during sex. Be sure to follow any instructions your doctor gives you. There have also been reports of the seeds moving through the bloodstream to other parts of the body, such as the lungs. As far as doctors can tell, this is uncommon and doesnt seem to cause any ill effects.

These precautions arent needed after HDR brachytherapy, because the radiation doesnt stay in the body after treatment.

Bowel problems: Brachytherapy can sometimes irritate the rectum and cause a condition called radiation proctitis. Bowel problems such as rectal pain, burning, and/or diarrhea can occur, but serious long-term problems are uncommon.

Surgical Implications Of Nadt

Neoadjuvant androgen deprivation therapy has been demonstrated to decrease prostate volume by 20-50%. The initial hope was that shrinking the gland would make radical prostatectomy technically easier, with less blood loss. The findings in this regard have been inconsistent.

In the multicenter, randomized T2bN0M0 trial, surgeons rated the difficulty of dissection, presence of seminal vesicle adherence, and extent of blood loss and found that seminal vesicle adherence to the periprostatic tissues was more common in patients pretreated with NADT than in those treated with surgery alone . They also recorded the operating time and amount of blood transfused. Surgical dissection was more difficult in pretreated patients. No significant difference in operating time, blood loss, or transfusion requirement occurred.

Although more dissections that were difficult were reported with NADT in this study, no operative complications occurred in the NADT group, whereas 6 intraoperative injuries were reported in patients who underwent surgery alone.

The authors believe that interference with apical dissection is potentially the most difficult problem caused by NADT. Also of serious concern is the fact that NADT-induced fibrosis can make intraoperative evaluation of the extent of the tumor more difficult, which in turn may compromise the extent of resection if the surgeon relies on intraoperative findings to determine performance of a nerve-sparing operation.

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Secondary Treatment Following Relapse

Hormone therapy may also be used as a secondary or salvage treatment when PSA levels rise following initial prostate cancer treatment, indicating the cancer has returned. This situation is known as biochemical recurrence. The salient points to keep in mind are that hormone therapy is most often used as a salvage treatment when PSA doubling time is less than six months, indicating that the cancer is aggressive or may have already metastasized.

Heres What The Study Found

How Radiation Affects The Prostate | Mark Scholz, MD

The newly published study randomly assigned 760 men with detectable PSA after surgery to one of two groups. One group got radiation plus ADT and the other group got radiation plus a daily placebo tablet. The study recruited patients between 1998 and 2003, and after an average follow-up of 12 years, 5.8% of men in the combined treatment group had died of prostate cancer, compared to 13.4% in the radiation-only group. Rates of metastatic prostate cancer were also lower among men treated with ADT: 14.5% compared to 23% among the placebo-treated controls.

The take-home message is that ADT has a major and beneficial impact on the risk of death from prostate cancer when added to radiation for PSA recurrence, said Ian Thompson, M.D., a professor of oncology at the UT School of Medicine, in San Antonio, Texas, and the author of an editorial accompanying the newly published findings.

Men in this study received a high dose of the ADT drug bicalutamide, which doctors use less frequently for PSA recurrence today, instead favoring other testosterone-suppressing medications that have since been shown to be more effective. Therefore this is an instance of a long-term study reporting results after treatment standards in this case the selection of a specific ADT regime have changed.

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Orchiectomy Surgical Removal Of The Testicles

Once a common treatment, orchiectomy is rarely used now, thanks to the development of advanced ADT drugs. The procedure removes the testicles the source of most testosterone production. The scrotal sac is left intact, and patients can have testicular prostheses implanted for cosmetic purposes. Orchiectomy is effective in drastically reducing levels of testosterone, but it has several downsides. Removal of the testicles is permanent and irreversible. Loss of the testicles makes it challenging to have intermittent hormone therapy, an advantageous treatment. And there is a psychological effect: Many patients feel distress related to the idea of lost masculinity if they undergo this procedure.

Staging Of Prostate Cancer

Doctors will use the results of your prostate examination, biopsy and scans to identify the stage of your prostate cancer .

The stage of the cancer will determine which types of treatments will be necessary.

If prostate cancer is diagnosed at an early stage, the chances of survival are generally good.

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