Treatment for Advanced Cancer

I came across the following in my research and it gave me some reason to pause and reconsider the way forward!

I'm due to see my Urologist on 14 February, we'll have a bit to talk about I think. On 8 February, I am due to have my next PSA test - hoping that the result is a continued improvement.

After 3 months [almost] on Hormone Therapy, I have seen my PSA level drop from '84.8' to '12' and [hopefully] to zero [or close to it] - this time.

Advanced Cancer

Patients with advanced prostate cancer are generally men who have extensive disease in the pelvis [No], metastases in the lymph nodes [No] or bone [No] or a PSA level greater than 50 ng/mL [Yes, 84.8 ... hmm, definitely me] or men in whom local treatment has failed [No].

Bilateral orchidectomy is the gold standard for testosterone reduction. However, although it offers immediate relief from metastatic pain and eliminates problems of compliance, orchidectomy is psychologically unacceptable to most men. Hormone therapy is the mainstay of treatment in this group.

When hormone therapy is commenced, the vast majority of patients get excellent initial symptomatic relief, even in the presence of painful metastases. Regular PSA measurements are the best way to monitor response. Some patients elect to delay hormone therapy in the interest of avoiding side effects. These men may have had a PSA recurrence after failed initial therapy or be older asymptomatic men with metastatic disease.

In patients who have less advanced disease the cancer ultimately becomes refractory [resistant] to hormone therapy' (after three to five years, or even longer).

Most patients who develop hormone refractory disease die within 12 months.

Which hormones should be used?

Leuprorelin acetate (Lucrin) and goserelin acetate (Zoladex), which are LHRH analogues, are commonly used for chemical castration. However, these agents cause an initial testosterone flare that should be prevented with concomitant use of an antiandrogen for the first two to four weeksí duration. LHRH analogues are available in monthly, three-monthly and, more recently, four-monthly depot preparations.

The nonsteroidal antiandrogens flutamide (Eulexin, Flutamin, Fugerel), bicalutamide (Cosudex) and nilutamide (Anandron) have similar action. These agents are generally used in association with LHRH analogues, but can be used alone in sexually active men to sometimes prevent impotence. Careful monitoring of liver function tests is essential in patients taking antiandrogens.

Cyproterone acetate (Androcur, Cyprone, Procur) is a steroidal antiandrogen that can be used alone or with LHRH analogues. Oestrogens have fallen out of favour because of their cardiovascular side effects.


Should hormones be commenced immediately or later, or intermittently?

Immediate hormone therapy is appropriate for symptomatic patients; however, its timing in asymptomatic patients remains controversial. There is increasing evidence to suggest that earlier use of hormone therapy improves survival, but this benefit must be balanced against side effects.

Most patients choose immediate therapy, although older asymptomatic patients may choose delayed therapy after informed consent. Patients with a PSA recurrence after previous failed surgery or radiotherapy often opt for a period of observation to ascertain the rate of PSA rise prior to commencing hormone therapy.

The use of intermittent hormone therapy has become increasingly popular in patients with less advanced disease. Although the benefits of intermittent therapy are less proven, it clearly improves quality of life in patients with less advanced disease who are destined to use hormones for very long periods.

The aim of this therapy is to depress PSA to undetectable levels, wait until it rises again to a predetermined level (such as 10 ng/mL), then commence a further pulse of hormones. This approach gives patients longer periods free of side effects of hormone therapy, such as impotence, depression, lethargy and osteoporosis.

How should hormone therapy be monitored?

Hormonal therapy is best monitored by regular measurement of PSA levels. To assess effectiveness in suppressing testosterone, a serum testosterone can be used and, if not completely suppressed, an anti-androgen can be added. A combination of castration (medical or surgical) and anti-androgen therapy may be used to block both testicular and adrenal androgen activity.

Since the results of major trials have recently become available, enthusiasm for this combination has decreased, but it still tends to be used in young men with early metastatic disease.


How should side effects of hormone therapy be managed?

The side effects of hormones must be managed individually. Hot flushes may be treated with cyproterone, clonidine (Catapres 100) or oestrogen; lethargy may be improved by giving hormones intermittently. Osteoporosis may develop in patients destined to use hormone therapy for long periods; in this group, bone density should be checked at 12 months and therapy such as intravenous or oral bisphosphonates should be used if significant deminerali-sation is present.


What can we do when hormones no longer work?

When hormone therapy fails, most treatment is palliative. Serum testosterone should always be checked to ensure hor-mone therapy has been achieving castrate levels of testosterone. Therapeutic options include:

Localised radiotherapy or strontium-89 (Metastron) radiotherapy to painful metastatic deposits - second-line hormone therapy - chemotherapy - cyclophosphamide (Cycloblastin, Endoxan-Asta), mitozantrone hydrochloride (Mitozantrone Injection, Novantrone, Onkotrone), docetaxel (Taxotere) - corticosteroids and pain relief.

A team approach to palliation is important to provide maximal quality of life in men who have hormone refractory cancer, and may include antidepressants, psychological support and hospice services. Promising new approaches include gene therapy, antiangiogenesis drugs such as thalidomide, immunological approaches, and growth factor blocking drugs.


Conclusion

It is mandatory to tailor therapy for prostate cancer to the individual. Modern treatments, including newer surgical techniques and improved conformal delivery of radiotherapy, have resulted in a significant decrease in side effects and improved outcomes. Further knowledge about biochemical markers, the results of new and improved techniques and more established results of known treatments will help us to individualise treatment, resulting in better control of the disease and fewer side effects.

Source: St Vincent's

Robotic Surgery

Further Research

I thought since I have already jumped ahead a few months by beginning to explore the various methods of 'radiotherapy'; that I may as well 'jump' to the next step, following that: i.e. 'Removal of the Prostate'. My surgeon intends to use the 'laporascopic method', rather than the more common 'open surgery' method. Whilst exploring these various options, I came across a radical, new technique now being used in Australia (and elsewhere).


The da Vinci PROSTATECTOMY Method

Da Vinci Robotic prostatectomy is the newest and most advanced surgical option for patients. This method gives a surgeon greater visualization, enhanced dexterity, precision, control and superior ergonomics. This very precise surgery only requires 5 small incisions (1cm) in the abdomen.


About the da Vinci Robotic System

The da Vinci Surgical System is powered by state-of-the-art robotic technology. The System allows your surgeon's hand movements to be scaled, filtered and translated into precise movements of micro-instruments within the operative site. The magnified, three-dimensional view the surgeon experiences enables him to perform precise surgery in complex procedures through small surgical incisions.

The da Vinci System enhances surgical capabilities by enabling the performance of complex surgeries through tiny surgical openings. The System cannot be programmed nor can it make decisions on its own. The da Vinci System requires that every surgical maneuver be performed with direct input from your surgeon. The da Vinci Surgical System has been successfully used in thousands of prostate cancer procedures world-wide.





For patients, there are numerous potential benefits including:

• Shorter hospital stay


• Less pain and less pain medication


• Less risk of infection


• Less blood loss


• Less scarring


• Faster and more complete recovery


• Quicker return to normal activities

Surgical Benefits:

• 3-D visualization provides the surgeon with a true 3-dimensional view of the operating field. This direct and natural hand-eye instrument alignment is similar to open surgery with all-around vision and the ability to zoom-in and zoom-out.


• Dexterity: the da Vinci Robotic System provides the surgeon with intuitive operative controls that allows the experienced surgeon to use his open surgery skills rather than having to use counter-intuitive motions typically required by a laparoscopic approach.


• Surgical Precision: permits the surgeon to manipulate instruments with such accuracy that the current definition of surgical precision is exceeded.


• Range of Motion: the robotic instruments offer the surgeon full range of motion and ability to rotate the instruments through tiny incisions.


• Ergonomics: the surgeon can sit in a comfortable position, allowing him to concentrate fully on the surgery.


• Improved Access: Surgeons perform complex surgical maneuvers through 1-cm ports, eliminating the need for large traumatic incisions.

Source: St Vincent's Clinic

Radiotherapy

Since my next challenge (after a successful 6 consecutive months of Hormone Therapy - in 4 months time) will be to undertake an 8 week course of Radiotherapy; I thought it prudent to take a closer look at the whole process.


Radiotherapy for Prostate cancer

Radiotherapy is a form of treatment that is used to treat cancer of the prostate gland. It may be used alone or in conjunction with surgery.

Radiotherapy involves the use of radiation which is targeted to the cancer site in order to destroy cancerous cells. Treatment is planned meticulously in order to minimise harm to normal cells. Treatment is usually carried out as an outpatient procedure, and lasts for several weeks (depending on the nature of the tumour).

There are different forms of radiotherapy for the prostate available.

Radiotherapy fights cancer by using high energy radiation to destroy cancer cells that multiply rapidly. It prevents the cancer cells from multiplying and stops the cancer from growing larger. It is a commonly recommended form of treatment as it is less invasive than surgery, and does not carry as many risks as surgery does.

During radiotherapy, patients will lie on a couch under a large x-ray machine. Each treatment lasts only for a few minutes and is not painful.


Forms of Radiotherapy

There is a wide range of forms of radiotherapy in treating cancer of the prostate:

1. External beam therapy:

• Divided into Standard External Beam Therapy and 3D Conformal Therapy.
  


• It delivers radiation beams targeted to the prostate.



• It is carried out as an outpatient procedure - patients do not have to stay in the hospital.



• 3D Conformal Therapy is a more updated method but is less widely available. It uses beams that are shaped to the outline of the prostate. Computer images are used to target the beams accurately.

2. Brachytherapy:

• It is a form of radiation therapy used in more localised prostate cancer, meaning cancer that is more confined to the prostate itself.
  


• In brachytherapy, the doctor implants radioactive seeds directly into the prostate.
  


• This enables the radiation to be given at a higher dose in a more concentrated manner.
  


• It is a fairly short procedure. Patients are usually required to stay in the hospital for only one night.

3. High Dose Rate (HDR) brachytherapy:

• It is usually combined with external radiotherapy.
  


• It is used to treat more advanced prostate cancer, where treatment is needed to cover the whole prostate and a margin.
  


• In HDR brachytherapy, thin stiff plastic tubes are inserted through the perineum (the area of skin behind the scrotum) and into the prostate. This is done under anaesthesia.
  


• A radiotherapy machine inserts a radioactive wire through each plastic tube and into the prostate. These wires are left in place for a few minutes and then removed.
  


• Patients stay in the hospital for one night. The next day the procedure of inserting and removing the radioactive wires is repeated. The procedure takes about half an hour.

HDR machine: The machine used in High Dose Rate (HDR) brachytherapy to insert radioactive wires through plastic tubes into the prostate. This is often used to treat prostate cancer at an advanced stage.

The Seeding Procedure:

The procedure in brachytherapy where radioactive seeds are implanted into the prostate to destroy cancer cells.

Under anaesthesia, thin stiff plastic tubes are inserted through the perineum (the area of skin behind the scrotum) and into the prostate. Radioactive wires are then inserted through the plastic tubes into the prostate, to implant radioactive seeds in the prostate.

Unseeded Prostate:

The image of a prostate before radioactive seeds are implanted.

Seeded Prostate:

The image of a prostate after the seeding procedure, where radioactive seeds are seen in the prostate gland. The radioactive seeds allow high dose radioactivity in the prostate to target cancer cells accurately while minimising damage to other body structures surrounding the prostate.


Advantages and Disadvantages of Radiotherapy

The option of radiotherapy as treatment for prostate cancer has the following advantages:

• It does not carry the risks of surgery, therefore it is useful in patients who cannot have surgery.
  


• It does not require long hospitalisation. Patients receiving external beam radiation does not even have to stay in the hospital - it is carried out as an outpatient procedure.
  


• Patients can return to normal life fairly soon, normally within a few days.
  

Disadvantages of radiotherapy:

• Tiredness, diarrhoea and cystitis (inflammation of the bladder causing a burning sensation when passing urine) are common short-term side effects.
  


• Damage to surrounding structures e.g. bladder, large bowel can sometimes occur, but this is uncommon as care is taken to minimise harm to structures other than the cancer cells.
  


• A small proportion of men (less than 5%) will have long-term bowel problems - bowel motions may become looser and more frequent. However, in most men these symptoms settle gradually.
  


• Patients receiving external beam therapy require frequent visits to the hospital radiotherapy unit as an outpatient for up to 6 weeks.

• There is a risk of impotence (inability to achieve and maintain an erection) and urinary incontinence (leakage of urine).
  

• The skin in the area where the treatment is targeted may become sore.

Source: Virtual Medicine

Detailed Guide Prostate Cancer: What's New in Prostate Cancer Research and Treatment?

Research into the causes, prevention, and treatment of prostate is under way in many medical centers throughout the world.


Genetics

New research on genes linked to prostate cancer is helping scientists better understand how prostate cancer develops. These studies are expected to provide answers about the genetic changes that lead to prostate cancer. This could make it possible to design medicines to reverse those changes. Tests to find abnormal prostate cancer genes could also help identify men at high risk who would benefit from more intensive screening or from chemoprevention trials, which use drugs to try to keep them from getting cancer.

Most of the genes that have been studied so far are from chromosomes that are inherited from both parents. One recent study found that a certain variant of mitochondrial DNA, which is inherited only from a person's mother, might double or even triple a man's risk of developing prostate cancer.

An exciting new development in genetics research is the use of DNA microarray technology which allows scientists to study thousands of genes at the same time. Using this method, researchers have identified several genes now thought to play a role in prostate cancer. This may eventually provide more sensitive screening tests for prostate cancer than the PSA blood test currently in use.

One of the biggest problems now facing men with prostate cancer and their doctors is figuring out which cancers are likely to stay within the gland and which are more likely to grow and spread (and definitely need treatment). New discoveries may help with this some time in the near future. For example, the product of one gene identified by DNA microarray, known as EZH2, seems to appear more often in advanced prostate cancers than in those at an early stage. Researchers are now trying to decide whether the presence of this gene product, or others, indicates that a cancer is more aggressive. This could eventually help tell which men need treatment and which might be better served by watchful waiting.


Prevention

Researchers continue to look for foods that increase or decrease prostate cancer risk. Scientists have found some substances in tomatoes (lycopenes) and soybeans (isoflavones) that may help prevent prostate cancer. Studies are now looking at the possible effects of these compounds more closely. Scientists are also trying to develop related compounds that are even more potent and might be used as dietary supplements. So far, most research suggests that a balanced diet including these foods as well as other fruits and vegetables is of greater benefit than taking these substances as dietary supplements.

Some studies suggest that certain vitamin and mineral supplements (such as vitamin E and selenium) may lower prostate cancer risk. A large study of this issue, called the Selenium and Vitamin E Cancer Prevention Trial (SELECT), is still in progress. Another vitamin that may be important is vitamin D. Recent studies have found that men with high levels of vitamin D seem to have a lower risk of developing the more lethal forms of prostate cancer.

Although many people assume that vitamins are natural substances that cause no harm, recent research has shown that high doses may be harmful. One study found that men who take more than 7 multivitamin tablets per week may have an increased risk of developing advanced prostate cancer.

Scientists are also testing certain hormonal medicines as a way of reducing prostate cancer risk. Finasteride (Proscar) and dutasteride (Avodart) are drugs that lower the body's levels of a potent androgen called DHT. Both drugs are already used to treat benign prostatic hyperplasia (BPH). The results of one such study, the Prostate Cancer Prevention Trial are discussed above in the section, "Can Prostate Cancer Be Prevented?" This study looked at the possible benefits of finasteride, although the results were not clear-cut. Another study is looking at whether dutasteride might be helpful in reducing the risk of getting prostate cancer.


Early Detection

Doctors agree that the PSA blood test is not a perfect test for finding prostate cancer early. It misses some cancers, and in other cases it is elevated when cancer isn't present. Researchers are working on two strategies to address this problem.

One approach is to try to improve on the test that measures the total PSA level, as described in the section, "Can Prostate Cancer Be Found Early?" The percent-free PSA is one way to do this, although it requires two separate tests. Another option might be to measure only the "complexed" PSA (the portion of PSA that is not "free") to begin with, instead of the total and free PSA. This one test could give the same amount of information as the other two done separately. Studies are now under way to see if this test provides the same level of accuracy.

The other approach is to develop new tests based on other tumor markers. Several newer blood tests seem to be more accurate than the PSA test, based on early studies. One example is a blood test for a marker called EPCA-2. Another approach is to look for signs of the body's own immune reaction to substances made by prostate cancer cells. While early results have been promising, these and other new tests are not yet available outside of research labs and will require more study before they are widely used to test for prostate cancer.


Diagnosis

Doctors performing prostate biopsies often rely on transrectal ultrasound (TRUS), which creates black and white images of the prostate using sound waves, to know where to take samples from. But standard ultrasound may not detect some areas containing cancer. A fairly new technique, known as color Doppler ultrasound, measures blood flow within the gland. (Tumors often have more blood vessels around them than normal tissue.) It may make prostate biopsies more accurate by helping to ensure the right part of the gland is sampled. An even newer technique may enhance color Doppler further. It involves first injecting the patient with a contrast agent containing microbubbles. Promising results have been reported, but more studies will be needed before its use becomes common.


Staging

Staging plays a key role in deciding which treatment options a man may be eligible for. But imaging tests for prostate cancer such as CT and MRI scans can't detect all cancers, especially small areas of cancer in lymph nodes. A newer method, called enhanced MRI, may help find lymph nodes that contain cancer. Patients first have a standard MRI. They are then injected with tiny magnetic particles and have another scan done the next day. Differences between the 2 scans point to possible cancer cells in the lymph nodes. Early results of this technique are promising, but it needs more research before it becomes widely used.


Treatment

This is a very active area of research. Newer treatments are being developed, and improvements are being made among many standard prostate cancer treatment methods.


Surgery

If the nerves that control erections (which run along either side of the prostate) must be removed during the operation, a man will become impotent. Some doctors are now exploring the use of sural nerve grafts to try to restore potency if the original nerves must be removed. This approach, done at the same time as the radical prostatectomy, involves replacing the original nerves with small nerves taken from the side of the foot. This is still considered an experimental technique, and not all doctors agree as to its usefulness. Further study is under way.


Radiation Therapy

As described in the section, "How Is Prostate Cancer Treated?" advances in technology are making it possible to aim radiation more precisely than in the past. Currently used methods such as conformal radiation therapy (CRT) and intensity modulated radiation therapy (IMRT) allow doctors to treat only the prostate gland and avoid radiation to normal tissues as much as possible. This is expected to increase the effectiveness and reduce the side effects of radiation therapy. Studies are being done to find out which radiation techniques are best suited for specific groups of patients with prostate cancer.

Newer forms of radiation therapy that deliver radiation from several angles, such as the CyberKnife and helical tomotherapy, may provide even more precise delivery of radiation to the prostate while sparing normal tissues. These newer approaches have only been available for a short time, so there is limited data on them.

Technology is making other forms of radiation therapy more effective as well. New computer programs allow doctors to better plan the radiation doses and approaches for both external radiation therapy and brachytherapy. Planning for brachytherapy can now even be done during the procedure (intraoperatively).


Newer Treatments for Localized Disease

Researchers are looking at newer forms of treatment for early stage prostate cancer. These new treatments could be used either as the first type of treatment or be used after radiation therapy in cases where it was not successful.

One promising treatment, known as high-intensity focused ultrasound (HIFU), destroys cancer cells by heating them with highly focused ultrasonic beams. While it has been used more in Europe, it is not commonly employed in the United States at this time. Studies are now under way to determine its safety and effectiveness.


Nutrition and Lifestyle Changes

A recent study found that in men with a rising PSA after surgery or radiation therapy, drinking pomegranate juice seemed to slow the time it took the PSA level to double. Larger studies are now under way to try to confirm these results.

Some encouraging early results have also been reported with flaxseed supplements. One small study in men with early prostate cancer found that daily flaxseed seemed to slow the rate at which prostate cancer cells multiplied. More research is needed to confirm this finding.

A recent report found that men who chose not to have treatment for their localized prostate cancer may be able to slow its growth with intensive lifestyle changes. The men ate a vegan (no meat, fish, eggs, or dairy products) diet and exercised frequently. They also took part in support groups and yoga. After one year the men saw, on average, a slight drop in their PSA level. It isn't known whether this effect will last since the report only followed the men for 1 year. The regimen may also be hard to follow for some men.


Chemotherapy

Studies in recent years have shown that many chemotherapy drugs can affect prostate cancer. At least one drug (docetaxel) has been shown to help men live longer. Several new chemotherapy drugs and combinations of drugs are now being studied.

One newer drug is satraplatin, which is in late-stage clinical trials as a second-line chemotherapy option for men with advanced, hormone-refractory prostate cancer. Satraplatin is taken as a pill. It is now being looked at by the FDA for possible approval.

Calcitriol, a form of vitamin D, has recently shown promising results when combined with docetaxel (Taxotere). Men who received the combination seemed to do better than men in other studies who received only docetaxel. A large clinical trial is now comparing a high-dose form of calcitriol (DN-101) and docetaxel to docetaxel alone.


Prostate Cancer Vaccines

Several types of vaccines for boosting the body's immune response to prostate cancer cells are being tested in clinical trials. Unlike vaccines against infections like measles or mumps, these vaccines are designed to help treat, not prevent, prostate cancer. One possible advantage of these types of treatments is that they seem to have very limited side effects. At this time, vaccines are only available in clinical trials.

The furthest along in terms of development is sipuleucel-T (Provenge). For this vaccine, dendritic cells (cells of the immune system) are removed from the patient's blood and exposed to a part of prostate cancer cells called prostatic acid phosphatase (PAP). These cells are then put back into the body where they induce other immune system cells to attack the patient's prostate cancer. A small study found that the vaccine seemed to increase survival in men with advanced, hormone-refractory prostate cancer, and further studies are under way. Provenge is now being looked at by the FDA for possible approval.

A vaccine known as GVAX has also shown promise against advanced, hormone-refractory prostate cancer in early studies. This vaccine is made up of prostate cancer cells that have been genetically modified to make GM-CSF, a substance that boosts the immune response against them. GVAX is now in late-stage clinical trials.

Another prostate cancer vaccine (PROSTVAC-VF) uses a virus that has been genetically modified to contain prostate-specific antigen (PSA). The patient's immune system should respond to the virus and begin to recognize and destroy cancer cells containing PSA. This vaccine is still in early-stage clinical trials.

Several other prostate cancer vaccines are also in development.


Monoclonal Antibodies

Monoclonal antibodies are manmade versions of immune system proteins designed to target specific molecules in prostate cancer cells. Several different ones are being developed and tested.

For example, pertuzumab is a monoclonal antibody directed against the HER2 protein, which is sometimes found in excess amounts on the surface of cancer cells. Studies of men with advanced, hormone-refractory prostate cancer have not found that pertuzumab shrinks tumors or lowers PSA levels, although one study found it may have helped men live longer than would be expected.


Angiogenesis Inhibitors

Growth of prostate cancer tumors depends on growth of blood vessels (angiogenesis) to nourish the cancer cells. Looking at angiogenesis in prostate cancer specimens may help predict treatment outcomes. Cancers that stimulate many new vessels to grow are harder to treat and have a poorer outlook.

New drugs are being studied that may be useful in stopping prostate cancer growth by keeping new blood vessels from forming. Several anti-angiogenic drugs are already being tested in clinical trials. One of these is thalidomide, which has been approved by the FDA to treat patients with multiple myeloma. It is being combined with chemotherapy in clinical trials to treat men with advanced prostate cancer. While promising, this drug can cause major side effects, including constipation, drowsiness, and nerve damage.

Another drug, bevacizumab (Avastin), is FDA-approved to treat patients with other cancers. It is now being tested in combination with hormone therapy and chemotherapy in men with advanced prostate cancer.


Treatment of Bone Pain

Doctors are now studying the use of radiofrequency ablation (RFA) to help control pain in men whose prostate cancer has spread to one or more areas in the bones. During RFA, the doctor uses computed tomography (CT) or ultrasound to guide a small metal probe into the area of the tumor. A high frequency current passed through the probe heats and destroys the tumor. While RFA has been used for many years to treat tumors in other organs such as the liver, its use in treating bone pain is still fairly new.

Source: American Cancer Society