Prostate cancer medical therapy: Difference between revisions

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{{CMG}}
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{{CMG}} {{AE}} {{sali}}
{{Prostate cancer}}
{{Prostate cancer}}


==Overview==
==Overview==
The predominant therapy for prostate cancer is [[surgical resection]]. Adjunctive [[chemotherapy]], [[radiation]], [[hormonal therapy]], [[bisphosphonates]], and [[analgesics]]  may be required.


==Therapy==
==Medical Therapy==
 
===Natural therapy===
As an alternative to active surveillance or invasive treatments, which does nothing to change the course of disease, a growing number of clinicians and researchers are looking at non-invasive ways to help men with apparently localized prostate cancer. Perhaps most convincing among this group are Dean Ornish, MD and colleagues, previously made famous for showing that aggressive lifestyle changes can reverse atherosclerosis, and now showing that PSA can be lowered in men with apparent localized prostate cancer using a vegan diet (fish allowed), regular exercise, and stress reduction.<ref>{{cite journal | last=Ornish| first=D| coauthors=Weidner G, Fair WR, et al.| title=Intensive lifestyle changes may affect the progression of prostate cancer| journal=J Urol| year=2005| volume=174| issue=3| pages=1065–70| pmid=16094059}}</ref> These results have so far proven durable after two-years' treatment.<ref>{{cite journal| last=Frattaroli| first=J| coauthors=Weidner G, Kemp C, et al.| title=Clinical events in Prostate CAncer Lifestyle Trial: Results from two years of follow-up| journal=Urology| year=2008| month=July| pmid= 18602144| volume=epub ahead of print}}</ref>
 
Many other single agents have been shown to reduce PSA, slow PSA doubling times, or have similar effects on secondary markers in men with localized cancer in short term trials, such as the Wonderful variety of pomegranate juice 8 oz daily or genistein, an isoflavone found in various legumes, 60 mg per day.<ref>{{cite journal| last=Pantuck| first=AJ| coauthors=Leppert JT, Zomorodian N, et al.| title=Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer| journal=Clin Cancer Res| year=2006| volume=12| issue=13| pages=4018–26| pmid=16818701}}</ref><ref>{{cite journal| last=Kumar| first=NB| coauthors=Cantor A, Allen K, et al.| title=The specific role of isoflavones in reducing prostate cancer risk| journal=Prostate| year=2004| volume=59| issue=2| pages=141–7| pmid= 15042614}}</ref> The potential of using multiple such agents in concert, let alone combining them with lifestyle changes, has not yet been studied but the potential is great. This is particularly true because most of these natural approaches have very low adverse effect rates, and in fact tend to help other risk factors and disease conditions such as atherosclerosis, diabetes, and risk for other cancers at the same time they are helping slow down prostate cancer. A more thorough review of natural approaches to prostate cancer has been published.<ref>{{cite journal| last=Yarnell| first=E| title=A naturopathic approach to prostate cancer. Part 2: Guidelines for treatment and prevention| journal=Altern Complemen Ther| year=1999| volume=5| issue=6| pages=360–8}}</ref>


===Radiation therapy===
===Radiation therapy===
[[Image:brachytherapy.jpg|thumb|left|250px|'''[[Brachytherapy]]''' for prostate cancer is administered using "seeds," small radioactive rods implanted directly into the tumor.]][[Radiation therapy]], also known as radiotherapy, is often used to treat all stages of prostate cancer, or when surgery fails.  Radiotherapy uses [[ionizing radiation]] to kill prostate cancer cells. When absorbed in tissue, [[Ionizing radiation]] such as Gamma and x-rays damage the [[DNA]] in cells, which increases the probability of apoptosis (cell death). Two different kinds of radiation therapy are used in prostate cancer treatment: [[external beam radiotherapy|external beam radiation therapy]] and [[brachytherapy]] (specifically prostate brachytherapy).  
* [[Radiotherapy]] uses [[ionizing radiation]] to kill [[prostate]] [[cancer]] cells. When absorbed in tissue, [[ionizing radiation]] such as [[Gamma]] and [[x-rays]] damage the [[DNA]] in cells, which increases the probability of [[apoptosis]].
 
* Radiation therapy is commonly used in prostate cancer treatment.
External beam radiation therapy uses a [[linear accelerator]] to produce high-energy x-rays which are directed in a beam towards the prostate. A technique called Intensity Modulated Radiation Therapy (IMRT) may be used to adjust the radiation beam to conform with the shape of the tumor, allowing higher doses to be given to the prostate and seminal vesicles with less damage to the bladder and rectum. External beam radiation therapy is generally given over several weeks, with daily visits to a radiation therapy center. New types of radiation therapy may have fewer side effects than traditional treatment. One of these is [[Tomotherapy]].
* It may be used instead of [[surgery]] or after surgery in early stage prostate cancer. [[Radiation therapy]] appears to cure small [[tumors]] that are confined to the prostate just about as well as surgery.<ref name="”cancergov”">National Cancer Institute. Physician Data Query Database 2015. http://www.cancer.gov/publications/pdq</ref>
 
* In advanced stages of prostate cancer, radiation is used to treat painful [[bone metastases]].
[[Image:linacprostate.jpg|thumb|right|150px|[[External beam radiotherapy|External beam radiation therapy]] for prostate cancer is delivered by a linear accelerator, such as this one.]]
* Radiation therapy is often offered to men whose medical problems make [[surgery]] more risky.
Permanent implant brachytherapy is a popular treatment choice for patients with low to intermediate risk features, can be performed on an outpatient basis, and is associated with good 10-year outcomes with relatively low morbidity<ref>{{cite journal| last=Nag| first=S| coauthors=Beyer D, Friedland J, Grimm P, Nath R| title=American Brachytherapy Society Recommendations for Transperineal Permanent Brachytherapy of Prostate Cancer | journal=Int. J. Rad. Onc. Biol. Phys. | year=1999| month=?| volume=44| issue=4| pages=789–799| id=?}} Review.</ref>  It involves the placement of about 100 small "seeds" containing radioactive material (such as [[iodine-125]] or [[palladium-103]]) with a needle through the skin of the [[perineum]] directly into the tumor while under spinal or general anesthetic. These seeds emit [[Superficial X-ray|lower-energy X-rays]] which are only able to travel a short distance. Although the seeds eventually become inert, they remain in the prostate permanently. The risk of exposure to others from men with implanted seeds is generally accepted to be insignificant.<ref>{{cite journal| last=Perez| first=CA| coauthors=Hanks GE, Leibel SA, Zietman AL, Fuks Z, Lee WR| title=Localized carcinoma of the prostate (stages T1B, T1C, T2, and T3). Review of management with external beam radiation therapy| journal=Cancer| year=1993| month=December 1| volume=72| issue=11| pages=3156–73| pmid=7694785| doi=10.1002/1097-0142(19931201)72:11<3156::AID-CNCR2820721106>3.0.CO;2-G}} Review.</ref>
* Two different kinds of radiation therapy are used in prostate cancer treatment:<ref name="”cancergov”">National Cancer Institute. Physician Data Query Database 2015. http://www.cancer.gov/publications/pdq</ref>
 
* Rising PSA on ADT, if testosterone level is not completely suppressed, luteinizing hormone (LH) can be measured.
Radiation therapy is commonly used in prostate cancer treatment. It may be used instead of surgery or after surgery in early stage prostate cancer. In advanced stages of prostate cancer radiation is used to treat painful bone metastases. Radiation treatments also can be combined with hormonal therapy for intermediate risk disease, when radiation therapy alone is less likely to cure the cancer. Some radiation oncologists combine external beam radiation and brachytherapy for intermediate to high risk situations. One study found that the combination of six months of androgen suppressive therapy combined with external beam radiation had improved survival compared to radiation alone in patients with localized prostate cancer.<ref>{{cite journal | author=D'Amico AV, Manola J, Loffredo M, Renshaw AA, DellaCroce A, Kantoff PW | title=6-month androgen suppression plus radiation therapy vs radiation therapy alone for patients with clinically localized prostate cancer: a randomized controlled trial | journal=JAMA | year=2004 | pages=821–7 | volume=292 | issue=7  | pmid=15315996 | doi = 10.1001/jama.292.7.821}}</ref> Others use a "triple modality" combination of external beam radiation therapy, brachytherapy, and hormonal therapy.
* If its non-suppressed LH, correct administration of the GnRH analogue can be verified.<ref name="pmid26041764">{{cite journal |vauthors=Gillessen S, Omlin A, Attard G, de Bono JS, Efstathiou E, Fizazi K, Halabi S, Nelson PS, Sartor O, Smith MR, Soule HR, Akaza H, Beer TM, Beltran H, Chinnaiyan AM, Daugaard G, Davis ID, De Santis M, Drake CG, Eeles RA, Fanti S, Gleave ME, Heidenreich A, Hussain M, James ND, Lecouvet FE, Logothetis CJ, Mastris K, Nilsson S, Oh WK, Olmos D, Padhani AR, Parker C, Rubin MA, Schalken JA, Scher HI, Sella A, Shore ND, Small EJ, Sternberg CN, Suzuki H, Sweeney CJ, Tannock IF, Tombal B |title=Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015 |journal=Ann Oncol |volume=26 |issue=8 |pages=1589–604 |date=August 2015 |pmid=26041764 |pmc=4511225 |doi=10.1093/annonc/mdv257 |url=}}</ref>
 
:* [[External beam radiotherapy|External beam radiation therapy]]
Radiation therapy uses high-energy rays or particles to kill cancer cells.<ref>[http://www.cancer.org/docroot/CRI/content/CRI_2_4_4X_Radiation_Therapy_36.asp?rnav=cri  American Cancer Society: Radiation Treatment]</ref>
:* [[Brachytherapy]]
When delivered in the correct dosage, radiation can reduce the risk of recurrence. 
 
Less common applications for radiotherapy are when cancer is compressing the spinal cord, or sometimes after surgery, such as when cancer is found in the seminal vesicles, in the lymph nodes, outside the prostate capsule, or at the margins of the biopsy.
 
Radiation therapy is often offered to men whose medical problems make surgery more risky. Radiation therapy appears to cure small tumors that are confined to the prostate just about as well as surgery. However, some issues remain unresolved, such as whether radiation should be given to the rest of the pelvis, how much the [[absorbed dose]] should be, and whether hormonal therapy should be given at the same time.


Side effects of radiation therapy might occur after a few weeks into treatment. Both types of radiation therapy may cause [[diarrhea]] and mild [[Gastrointestinal bleeding|rectal bleeding]] due to [[radiation proctitis]], as well as urinary incontinence and impotence. Symptoms tend to improve over time.  Rates for impotence when comparing radiation to nerve-sparing surgery are similar.  Radiation has lower rates of incontinence but higher rates of occasional mild rectal bleeding.<ref>{{cite journal| last=Lawton| first=CA| coauthors=Won M, Pilepich MV, Asbell SO, Shipley WU, Hanks GE, Cox JD, Perez CA, Sause WT, Doggett SR, et al| title=Long-term treatment sequelae following external beam irradiation for adenocarcinoma of the prostate: analysis of RTOG studies 7506 and 7706| journal=Int J Radiat Oncol Biol Phys| year=1991| month=September| volume=21| issue=4| pages=935–9| pmid=1917622}}</ref> Men who have undergone external beam radiation therapy may have a slightly higher risk of later developing [[colon cancer]] and [[bladder cancer]].<ref>{{cite journal| last=Brenner| first=DJ| coauthors=Curtis RE, Hall EJ, Ron E| title=Second malignancies in prostate carcinoma patients after radiotherapy compared with surgery| journal=Cancer| year=2000| month=January 15| volume=88| issue=2| pages=398–406| pmid=10640974| doi=10.1002/(SICI)1097-0142(20000115)88:2<398::AID-CNCR22>3.0.CO;2-V}}</ref>
====Side effects of radiation therapy====
* Both types of [[radiation therapy]] have following adverse effects:<ref>{{cite journal| last=Lawton| first=CA| coauthors=Won M, Pilepich MV, Asbell SO, Shipley WU, Hanks GE, Cox JD, Perez CA, Sause WT, Doggett SR, et al| title=Long-term treatment sequelae following external beam irradiation for adenocarcinoma of the prostate: analysis of RTOG studies 7506 and 7706| journal=Int J Radiat Oncol Biol Phys| year=1991| month=September| volume=21| issue=4| pages=935–9| pmid=1917622}}</ref><ref>{{cite journal| last=Lawton| first=CA| coauthors=Won M, Pilepich MV, Asbell SO, Shipley WU, Hanks GE, Cox JD, Perez CA, Sause WT, Doggett SR, et al| title=Long-term treatment sequelae following external beam irradiation for adenocarcinoma of the prostate: analysis of RTOG studies 7506 and 7706| journal=Int J Radiat Oncol Biol Phys| year=1991| month=September| volume=21| issue=4| pages=935–9| pmid=1917622}}</ref>
:* [[Diarrhea]]
:* Mild [[Gastrointestinal bleeding|rectal bleeding]]
* [[External beam radiotherapy|External beam radiation therapy]] has following adverse effects:<ref>{{cite journal| last=Brenner| first=DJ| coauthors=Curtis RE, Hall EJ, Ron E| title=Second malignancies in prostate carcinoma patients after radiotherapy compared with surgery| journal=Cancer| year=2000| month=January 15| volume=88| issue=2| pages=398–406| pmid=10640974| doi=10.1002/(SICI)1097-0142(20000115)88:2<398::AID-CNCR22>3.0.CO;2-V}}</ref>
:* [[Colon cancer]]
:* [[Bladder cancer]]


===Hormonal therapy===
===Hormonal therapy===
[[Image:prostatehormone.jpg|right|thumb|200px|'''Hormonal therapy in prostate cancer.''' Diagram shows the different organs (''purple text''), hormones (''black text and arrows''), and treatments (''red text and arrows'') important in hormonal therapy.]] 
* [[Hormonal therapy (oncology)|Hormonal therapy]] uses medications or surgery to block prostate cancer cells from getting [[dihydrotestosterone]] ([[Dihydrotestosterone|DHT]]), a hormone produced in the prostate and required for the growth and spread of most prostate cancer cells. Blocking [[Dihydrotestosterone|DHT]] often causes prostate cancer to stop growing and even shrink.<ref>{{cite journal| last=Robson| first=M|author2=Dawson N| title=How is androgen-dependent metastatic prostate cancer best treated?| journal=Hematol Oncol Clin North Am|date=June 1996| volume=10| issue=3| pages=727–47| pmid=8773508|doi=10.1016/S0889-8588(05)70364-6}} Review.</ref>
[[Hormonal therapy (oncology)|Hormonal therapy]] uses medications or surgery to block prostate cancer cells from getting [[dihydrotestosterone]] (DHT), a hormone produced in the prostate and required for the growth and spread of most prostate cancer cells. Blocking DHT often causes prostate cancer to stop growing and even shrink. However, hormonal therapy rarely cures prostate cancer because cancers which initially respond to hormonal therapy typically become resistant after one to two years. Hormonal therapy is therefore usually used when cancer has spread from the prostate. It may also be given to certain men undergoing radiation therapy or surgery to help prevent return of their cancer.<ref>{{cite journal| last=Robson| first=M| coauthors=Dawson N| title=How is androgen-dependent metastatic prostate cancer best treated?| journal=Hematol Oncol Clin North Am| year=1996| month=June| volume=10| issue=3| pages=727–47| pmid=8773508| doi=10.1016/S0889-8588(05)70364-6}} Review.</ref>
* Hormonal therapy for prostate cancer targets the pathways the body uses to produce [[DHT]]. A [[feedback loop]] involving [[testicles]], [[hypothalamus]], [[pituitary]], [[adrenal]], and prostate glands to control the blood levels of [[DHT]]. First, low blood levels of [[DHT]] stimulate the [[hypothalamus]] to produce [[gonadotropin releasing hormone]] (GnRH). GnRH then stimulates the [[pituitary gland]] to produce [[luteinizing hormone]] (LH), and LH stimulates the [[testicles]] to produce testosterone. Finally, [[testosterone]] from the [[testicles]] and [[dehydroepiandrosterone]] from the [[adrenal gland]]s stimulate the prostate to produce more DHT. Hormonal therapy can decrease levels of DHT by interrupting this pathway at any point.
* Hormonal therapy rarely cures prostate cancer because cancers which initially respond to hormonal therapy typically become resistant after one to two years. Hormonal therapy is therefore usually used when cancer has spread from the prostate.<ref>{{cite journal| last=Robson| first=M|author2=Dawson N| title=How is androgen-dependent metastatic prostate cancer best treated?| journal=Hematol Oncol Clin North Am|date=June 1996| volume=10| issue=3| pages=727–47| pmid=8773508|doi=10.1016/S0889-8588(05)70364-6}} Review.</ref>
* It may also be given to certain men undergoing radiation therapy or surgery to help prevent return of their cancer.<ref>{{cite journal| last=Robson| first=M| coauthors=Dawson N| title=How is androgen-dependent metastatic prostate cancer best treated?| journal=Hematol Oncol Clin North Am| year=1996| month=June| volume=10| issue=3| pages=727–47| pmid=8773508| doi=10.1016/S0889-8588(05)70364-6}} Review.</ref>


Hormonal therapy for prostate cancer targets the pathways the body uses to produce DHT. A [[feedback loop]] involving the testicles, the hypothalamus, and the pituitary, adrenal, and prostate glands controls the blood levels of DHT. First, low blood levels of DHT stimulate the [[hypothalamus]] to produce [[gonadotropin releasing hormone]] (GnRH). GnRH then stimulates the [[pituitary gland]] to produce [[luteinizing hormone]] (LH), and LH stimulates the [[testicles]] to produce testosterone. Finally, testosterone from the testicles and dehydroepiandrosterone from the [[adrenal gland]]s stimulate the prostate to produce more DHT. Hormonal therapy can decrease levels of DHT by interrupting this pathway at any point.
* There are several forms of hormonal therapy:<ref name="”cancergov”">National Cancer Institute. Physician Data Query Database 2015. http://www.cancer.gov/publications/pdq</ref><ref>{{cite journal| last=Loblaw| first=DA| coauthors=Mendelson DS, Talcott JA, Virgo KS, Somerfield MR, Ben-Josef E, Middleton R, Porterfield H, Sharp SA, Smith TJ, Taplin ME, Vogelzang NJ, Wade JL Jr, Bennett CL, Scher HI; American Society of Clinical Oncology| title=American Society of Clinical Oncology recommendations for the initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer| journal=J Clin Oncol| year=2004| month=July 15| volume=22| issue=14| pages=2927–41| pmid=15184404| doi=10.1200/JCO.2004.04.579}} Erratum in: J Clin Oncol. 2004 November 1;22(21):4435.</ref>
There are several forms of hormonal therapy:  
:* [[Antiandrogens]]
::* [[Flutamide]]
::* [[Bicalutamide]]
::* [[Nilutamide]]
::* [[Cyproterone acetate]]  
:* [[Gonadotropin-releasing hormone analog|GnRH antagonists]]
:* [[Estrogen ]]
:* Antiadrenal therapy
::* [[Ketoconazole]]
::* [[Aminoglutethimide]]


*[[Castration|Orchiectomy]] is surgery to remove the testicles. Because the testicles make most of the body's testosterone, after orchiectomy testosterone levels drop. Now the prostate not only lacks the testosterone stimulus to produce DHT, but also it does not have enough testosterone to transform into DHT.
=== Chemotherapy ===
*[[Antiandrogens]] are medications such as [[flutamide]], [[bicalutamide]], [[nilutamide]], and [[cyproterone acetate]] which directly block the actions of testosterone and DHT within prostate cancer cells.
* [[Chemotherapy]] is used in the treatment of castrate resistant prostate cancer (also called hormone-refractory prostate cancer).
*Medications which block the production of adrenal androgens such as DHEA include [[ketoconazole]] and [[aminoglutethimide]]. Because the adrenal glands only make about 5% of the body's androgens, these medications are generally used only in combination with other methods that can block the 95% of androgens made by the testicles. These combined methods are called total androgen blockade (TAB). TAB can also be achieved using antiandrogens.
* The most commonly used regimen combines the chemotherapeutic drug liste below:
*GnRH action can be interrupted in one of two ways. [[Gonadotropin-releasing hormone analog|GnRH antagonists]] suppress the production of LH directly, while [[Gonadotropin-releasing hormone analog|GnRH agonists]] suppress LH through the process of [[downregulation]] after an initial stimulation effect. [[Abarelix]] is an example of a GnRH antagonist, while the GnRH agonists include [[leuprolide]], [[goserelin]], [[triptorelin]], and [[buserelin]]. Initially, GnRH agonists ''increase'' the production of LH. However, because the constant supply of the medication does not match the body's natural production rhythm, production of both LH and GnRH decreases after a few weeks.<ref>{{cite journal| last=Loblaw| first=DA| coauthors=Mendelson DS, Talcott JA, Virgo KS, Somerfield MR, Ben-Josef E, Middleton R, Porterfield H, Sharp SA, Smith TJ, Taplin ME, Vogelzang NJ, Wade JL Jr, Bennett CL, Scher HI; American Society of Clinical Oncology| title=American Society of Clinical Oncology recommendations for the initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer| journal=J Clin Oncol| year=2004| month=July 15| volume=22| issue=14| pages=2927–41| pmid=15184404| doi=10.1200/JCO.2004.04.579}} Erratum in: J Clin Oncol. 2004 November 1;22(21):4435.</ref>
:* [[Docetaxel]]
*A very recent Trial I study (N=21) found that [[Abiraterone|Abiraterone Acetate]] caused dramatic reduction in [[PSA]] levels and [[Tumor]] sizes in aggressive end-stage prostate cancer for 70% of patients.  This is prostate cancer that resists all other treatments (e.g., castration, other hormones, etc.).  Officially the impacts on life-span are not yet known because subjects have not been taking the drug very long.  Larger Trial III Clinical Studies are in the works.  If successful an approved treatment is hoped for around 2011.<ref>{{cite journal| last=de Bono| first=Johann| coauthors= Gerhardt Attard, Alison H.M. Reid, Timothy A. Yap, Florence Raynaud, Mitch Dowsett, Sarah Settatree, Mary Barrett, Christopher Parker, Vanessa Martins, Elizabeth Folkerd, Jeremy Clark, Colin S. Cooper, Stan B. Kaye, David Dearnaley, Gloria Lee | title= Phase I Clinical Trial of a Selective Inhibitor of CYP17, Abiraterone Acetate, Confirms That Castration-Resistant Prostate Cancer Commonly Remains Hormone Driven| url = http://jco.ascopubs.org/cgi/content/abstract/JCO.2007.15.9749v1 | journal=J Clin Oncol| year=2004| month=July 21| volume= | issue= | pages= online| pmid=15184404| doi=10.1200/JCO.2007.15.9749| nopp=true}} Erratum in: J Clin Oncol. Early Release, published ahead of print July 21, 2008</ref><ref>{{ cite news | author = Richard Warry |  title =  Drug for deadly prostate cancer  |  url = http://news.bbc.co.uk/2/hi/health/7517414.stm | publisher = [[BBC]] | date = July 22, 2008  | accessdate = 2008-07-23 }}</ref>
:* [[Abiraterone]]
:* [[Corticosteroid]]
::* [[Prednisone]]<ref>{{cite journal| last=Tannock| first=IF| coauthors=de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S, Theodore C, James ND, Turesson I, Rosenthal MA, Eisenberger MA; TAX 327 Investigators| title=Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer| journal=N Engl J Med| year=2004| month=October 7| volume=351| issue=15| pages=1502–12| pmid=1547021| doi=10.1056/NEJMoa040720}}</ref>


The most successful hormonal treatments are orchiectomy and GnRH agonists. Despite their higher cost, GnRH agonists are often chosen over orchiectomy for cosmetic and emotional reasons. Eventually, total androgen blockade may prove to be better than orchiectomy or GnRH agonists used alone.  
===Other Medications===
* [[Bisphosphonates]]
:* [[Bisphosphonates]] such as [[zoledronic acid]] have been shown to delay [[skeletal]] [[complications]] such as [[fracture]]s or the need for [[radiation therapy]] in patients with hormone-refractory [[metastatic]] prostate cancer.<ref>{{cite journal | author=Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L, Chin JL, Vinholes JJ, Goas JA, Chen B | title=A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma | journal=J Natl Cancer Inst | year=2002 | pages=1458–68 | volume=94 | issue=19  | pmid=12359855}}</ref> 
* [[Analgesics]]
:* [[Bone pain]] due to [[metastatic]] disease is treated with [[opioid]]. [[Analgesic|Pain relievers]] such as [[morphine]] and [[oxycodone]].


Each treatment has disadvantages which limit its use in certain circumstances. Although orchiectomy is a low-risk surgery, the psychological impact of removing the testicles can be significant. The loss of testosterone also causes [[Hot flush|hot flashes]], weight gain, loss of [[libido]], enlargement of the [[breast]]s ([[gynecomastia]]), impotence and [[osteoporosis]]. GnRH agonists eventually cause the same side effects as orchiectomy but may cause worse symptoms at the beginning of treatment. When GnRH agonists are first used, testosterone surges can lead to increased bone pain from metastatic cancer, so antiandrogens or abarelix are often added to blunt these side effects. Estrogens are not commonly used because they increase the risk for [[cardiovascular disease]] and [[thrombosis|blood clots]]. The antiandrogens do not generally cause impotence and usually cause less loss of bone and muscle mass. Ketoconazole can cause [[Hepatotoxicity|liver damage]] with prolonged use, and aminoglutethimide can cause skin [[rash]]es.
==References==
{{Reflist|2}}


=== Palliative care ===
[[Category:Disease]]
[[Palliative care]] for advanced stage prostate cancer focuses on extending life and relieving the symptoms of metastatic disease. As noted above [[Abiraterone|Abiraterone Acetate]] is showing some promise in treating advance stage prostate cancer.  It causes a dramatic reduction in [[Prostate specific antigen|PSA]] levels and [[Tumor]] sizes in aggressive advanced-stage prostate cancer for 70% of patients.  [[Chemotherapy]] may be offered to slow disease progression and postpone symptoms. The most commonly used regimen combines the chemotherapeutic drug [[docetaxel]] with a [[corticosteroid]] such as [[prednisone]].<ref>{{cite journal| last=Tannock| first=IF| coauthors=de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S, Theodore C, James ND, Turesson I, Rosenthal MA, Eisenberger MA; TAX 327 Investigators| title=Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer| journal=N Engl J Med| year=2004| month=October 7| volume=351| issue=15| pages=1502–12| pmid=1547021| doi=10.1056/NEJMoa040720}}</ref> [[Bisphosphonates]] such as [[zoledronic acid]] have been shown to delay skeletal complications such as [[fracture]]s or the need for radiation therapy in patients with hormone-refractory metastatic prostate cancer.<ref>{{cite journal | author=Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L, Chin JL, Vinholes JJ, Goas JA, Chen B | title=A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma | journal=J Natl Cancer Inst | year=2002 | pages=1458–68 | volume=94 | issue=19  | pmid=12359855}}</ref> 
[[Category:Urology]]
[[Category:Types of cancer]]


[[Bone pain]] due to metastatic disease is treated with [[opioid]] [[Analgesic|pain relievers]] such as [[morphine]] and [[oxycodone]]. External beam radiation therapy directed at bone metastases may provide [[pain]] relief. Injections of certain [[radioisotope]]s, such as [[strontium-89]], [[phosphorus-32]], or [[samarium-153-ethylene diamine tetramethylene phosphonate|samarium-153]], also target bone metastases and may help relieve pain.
{{WH}}
 
{{WS}}
==References==
[[Category:Urology]]
{{Reflist|2}}
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]

Latest revision as of 18:54, 8 February 2021


Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Syed Musadiq Ali M.B.B.S.[2]

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Overview

The predominant therapy for prostate cancer is surgical resection. Adjunctive chemotherapy, radiation, hormonal therapy, bisphosphonates, and analgesics may be required.

Medical Therapy

Radiation therapy

  • Radiotherapy uses ionizing radiation to kill prostate cancer cells. When absorbed in tissue, ionizing radiation such as Gamma and x-rays damage the DNA in cells, which increases the probability of apoptosis.
  • Radiation therapy is commonly used in prostate cancer treatment.
  • It may be used instead of surgery or after surgery in early stage prostate cancer. Radiation therapy appears to cure small tumors that are confined to the prostate just about as well as surgery.[1]
  • In advanced stages of prostate cancer, radiation is used to treat painful bone metastases.
  • Radiation therapy is often offered to men whose medical problems make surgery more risky.
  • Two different kinds of radiation therapy are used in prostate cancer treatment:[1]
  • Rising PSA on ADT, if testosterone level is not completely suppressed, luteinizing hormone (LH) can be measured.
  • If its non-suppressed LH, correct administration of the GnRH analogue can be verified.[2]

Side effects of radiation therapy

Hormonal therapy

  • Hormonal therapy uses medications or surgery to block prostate cancer cells from getting dihydrotestosterone (DHT), a hormone produced in the prostate and required for the growth and spread of most prostate cancer cells. Blocking DHT often causes prostate cancer to stop growing and even shrink.[6]
  • Hormonal therapy for prostate cancer targets the pathways the body uses to produce DHT. A feedback loop involving testicles, hypothalamus, pituitary, adrenal, and prostate glands to control the blood levels of DHT. First, low blood levels of DHT stimulate the hypothalamus to produce gonadotropin releasing hormone (GnRH). GnRH then stimulates the pituitary gland to produce luteinizing hormone (LH), and LH stimulates the testicles to produce testosterone. Finally, testosterone from the testicles and dehydroepiandrosterone from the adrenal glands stimulate the prostate to produce more DHT. Hormonal therapy can decrease levels of DHT by interrupting this pathway at any point.
  • Hormonal therapy rarely cures prostate cancer because cancers which initially respond to hormonal therapy typically become resistant after one to two years. Hormonal therapy is therefore usually used when cancer has spread from the prostate.[7]
  • It may also be given to certain men undergoing radiation therapy or surgery to help prevent return of their cancer.[8]
  • There are several forms of hormonal therapy:[1][9]

Chemotherapy

  • Chemotherapy is used in the treatment of castrate resistant prostate cancer (also called hormone-refractory prostate cancer).
  • The most commonly used regimen combines the chemotherapeutic drug liste below:

Other Medications

References

  1. ↑ 1.0 1.1 1.2 National Cancer Institute. Physician Data Query Database 2015. http://www.cancer.gov/publications/pdq
  2. ↑ Gillessen S, Omlin A, Attard G, de Bono JS, Efstathiou E, Fizazi K, Halabi S, Nelson PS, Sartor O, Smith MR, Soule HR, Akaza H, Beer TM, Beltran H, Chinnaiyan AM, Daugaard G, Davis ID, De Santis M, Drake CG, Eeles RA, Fanti S, Gleave ME, Heidenreich A, Hussain M, James ND, Lecouvet FE, Logothetis CJ, Mastris K, Nilsson S, Oh WK, Olmos D, Padhani AR, Parker C, Rubin MA, Schalken JA, Scher HI, Sella A, Shore ND, Small EJ, Sternberg CN, Suzuki H, Sweeney CJ, Tannock IF, Tombal B (August 2015). "Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) 2015". Ann Oncol. 26 (8): 1589–604. doi:10.1093/annonc/mdv257. PMC 4511225. PMID 26041764.
  3. ↑ Lawton, CA (1991). "Long-term treatment sequelae following external beam irradiation for adenocarcinoma of the prostate: analysis of RTOG studies 7506 and 7706". Int J Radiat Oncol Biol Phys. 21 (4): 935–9. PMID 1917622. Unknown parameter |month= ignored (help); Unknown parameter |coauthors= ignored (help)
  4. ↑ Lawton, CA (1991). "Long-term treatment sequelae following external beam irradiation for adenocarcinoma of the prostate: analysis of RTOG studies 7506 and 7706". Int J Radiat Oncol Biol Phys. 21 (4): 935–9. PMID 1917622. Unknown parameter |month= ignored (help); Unknown parameter |coauthors= ignored (help)
  5. ↑ Brenner, DJ (2000). "Second malignancies in prostate carcinoma patients after radiotherapy compared with surgery". Cancer. 88 (2): 398–406. doi:10.1002/(SICI)1097-0142(20000115)88:2<398::AID-CNCR22>3.0.CO;2-V. PMID 10640974. Unknown parameter |month= ignored (help); Unknown parameter |coauthors= ignored (help)
  6. ↑ Robson, M; Dawson N (June 1996). "How is androgen-dependent metastatic prostate cancer best treated?". Hematol Oncol Clin North Am. 10 (3): 727–47. doi:10.1016/S0889-8588(05)70364-6. PMID 8773508. Review.
  7. ↑ Robson, M; Dawson N (June 1996). "How is androgen-dependent metastatic prostate cancer best treated?". Hematol Oncol Clin North Am. 10 (3): 727–47. doi:10.1016/S0889-8588(05)70364-6. PMID 8773508. Review.
  8. ↑ Robson, M (1996). "How is androgen-dependent metastatic prostate cancer best treated?". Hematol Oncol Clin North Am. 10 (3): 727–47. doi:10.1016/S0889-8588(05)70364-6. PMID 8773508. Unknown parameter |month= ignored (help); Unknown parameter |coauthors= ignored (help) Review.
  9. ↑ Loblaw, DA (2004). "American Society of Clinical Oncology recommendations for the initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer". J Clin Oncol. 22 (14): 2927–41. doi:10.1200/JCO.2004.04.579. PMID 15184404. Unknown parameter |month= ignored (help); Unknown parameter |coauthors= ignored (help) Erratum in: J Clin Oncol. 2004 November 1;22(21):4435.
  10. ↑ Tannock, IF (2004). "Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer". N Engl J Med. 351 (15): 1502–12. doi:10.1056/NEJMoa040720. PMID 1547021. Unknown parameter |month= ignored (help); Unknown parameter |coauthors= ignored (help)
  11. ↑ Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L, Chin JL, Vinholes JJ, Goas JA, Chen B (2002). "A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma". J Natl Cancer Inst. 94 (19): 1458–68. PMID 12359855.

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