Prostate cancer medical therapy: Difference between revisions

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__NOTOC__
__NOTOC__
{{CMG}}
 
{{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.


==Medical Therapy==
==Medical Therapy==


===Radiation 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]].
* [[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
* 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.
* 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]].
* 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.
* 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:  
* 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.
* 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]]
:* [[External beam radiotherapy|External beam radiation therapy]]
:* [[Brachytherapy]]
:* [[Brachytherapy]]


====Side effects of radiation therapy====
====Side effects of radiation therapy====
* Both types 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]]
:* [[Diarrhea]]
:* Mild [[Gastrointestinal bleeding|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>
:* Mild [[Gastrointestinal bleeding|rectal bleeding]]
* [[External beam radiotherapy|External beam radiation therapy]]
* [[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]]  
:* [[Colon cancer]]  
:* [[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>
:* [[Bladder cancer]]


===Hormonal therapy===
===Hormonal therapy===
* [[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.
* [[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 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.
* 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.
* 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.
* 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>
* 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>


* There are several forms of hormonal therapy:  
* 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>  
 
:* [[Antiandrogens]]  
*[[Castration|Orchiectomy]]
::* [[Flutamide]]  
*[[Antiandrogens]] are medications such as
::* [[Bicalutamide]]
:* [[flutamide]],
::* [[Nilutamide]]
[[bicalutamide]],
::* [[Cyproterone acetate]]  
[[nilutamide]], and
:* [[Gonadotropin-releasing hormone analog|GnRH antagonists]]
[[cyproterone acetate]] which directly block the actions of testosterone and DHT within prostate cancer cells.
:* [[Estrogen ]]
*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.
:* Antiadrenal therapy
*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>  
::* [[Ketoconazole]]
*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>
::* [[Aminoglutethimide]]
 
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.
 
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.
 
===Cardiovascular Effects of Androgen Suppression Therapy in Prostate Cancer===
 
Androgen suppression therapy, which includes [[GnRH agonist]], [[antiandrogens]] and [[orchiectomy|bilateral orchiectomy]], is used for the treatment of [[prostate cancer]].  Androgen suppression therapy use has been associated with increased incidence of cardiovascular risk factors.  In fact, androgen suppression therapy contributes to an increase in [[obesity]], modification of the body composition, a decrease in [[insulin sensitivity]] and [[dyslipidemia]].<ref name="pmid20124128">{{cite journal| author=Levine GN, D'Amico AV, Berger P, Clark PE, Eckel RH, Keating NL et al.| title=Androgen-deprivation therapy in prostate cancer and cardiovascular risk: a science advisory from the American Heart Association, American Cancer Society, and American Urological Association: endorsed by the American Society for Radiation Oncology. | journal=Circulation | year= 2010 | volume= 121 | issue= 6 | pages= 833-40 | pmid=20124128 | doi=10.1161/CIRCULATIONAHA.109.192695 | pmc=PMC3023973 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20124128  }} </ref>  The science advisory from the American Heart Association, American Cancer Society, and American Urological Association recommends regular follow up for the evaluation of cardiovascular risk factors among patients with [[prostate cancer]] on androgen suppression therapy.  Among patients with pre-existing cardiovascular disease, secondary prevention should be optimized.<ref name="pmid20124128">{{cite journal| author=Levine GN, D'Amico AV, Berger P, Clark PE, Eckel RH, Keating NL et al.| title=Androgen-deprivation therapy in prostate cancer and cardiovascular risk: a science advisory from the American Heart Association, American Cancer Society, and American Urological Association: endorsed by the American Society for Radiation Oncology. | journal=Circulation | year= 2010 | volume= 121 | issue= 6 | pages= 833-40 | pmid=20124128 | doi=10.1161/CIRCULATIONAHA.109.192695 | pmc=PMC3023973 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20124128  }} </ref>
 
In addition, androgen suppression therapy use is associated with increased risk of [[myocardial infarction]] (MI), [[stroke]]<ref name="pmid23433805">{{cite journal| author=Jespersen CG, Nørgaard M, Borre M| title=Androgen-deprivation Therapy in Treatment of Prostate Cancer and Risk of Myocardial Infarction and Stroke: A Nationwide Danish Population-based Cohort Study. | journal=Eur Urol | year= 2014 | volume= 65 | issue= 4 | pages= 704-9 | pmid=23433805 | doi=10.1016/j.eururo.2013.02.002 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23433805  }} </ref> and shorter time to [[MI]].<ref name="pmid17557956">{{cite journal| author=D'Amico AV, Denham JW, Crook J, Chen MH, Goldhaber SZ, Lamb DS et al.| title=Influence of androgen suppression therapy for prostate cancer on the frequency and timing of fatal myocardial infarctions. | journal=J Clin Oncol | year= 2007 | volume= 25 | issue= 17 | pages= 2420-5 | pmid=17557956 | doi=10.1200/JCO.2006.09.3369 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17557956  }} </ref>  A cohort of 73,196 patients with [[prostate cancer]], among which one third received [[GnRH agonist]] revealed an association between [[GnRH agonist]] use and increased incidence of [[diabetes]] (HR=1.44; P < 0.001), [[coronary heart disease]] (HR=1.16; P < 0.001) and [[MI]] (HR=1.11; P = 0.03).<ref name="pmid16983113">{{cite journal| author=Keating NL, O'Malley AJ, Smith MR| title=Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. | journal=J Clin Oncol | year= 2006 | volume= 24 | issue= 27 | pages= 4448-56 | pmid=16983113 | doi=10.1200/JCO.2006.06.2497 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16983113  }} </ref>
 
The association between androgen suppression therapy use and increased cardiovascular mortality is controversial.  While this association has been reported in some studies,<ref name="pmid17925537">{{cite journal| author=Tsai HK, D'Amico AV, Sadetsky N, Chen MH, Carroll PR| title=Androgen deprivation therapy for localized prostate cancer and the risk of cardiovascular mortality. | journal=J Natl Cancer Inst | year= 2007 | volume= 99 | issue= 20 | pages= 1516-24 | pmid=17925537 | doi=10.1093/jnci/djm168 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17925537  }} </ref><ref name="pmid20567006">{{cite journal| author=Van Hemelrijck M, Garmo H, Holmberg L, Ingelsson E, Bratt O, Bill-Axelson A et al.| title=Absolute and relative risk of cardiovascular disease in men with prostate cancer: results from the Population-Based PCBaSe Sweden. | journal=J Clin Oncol | year= 2010 | volume= 28 | issue= 21 | pages= 3448-56 | pmid=20567006 | doi=10.1200/JCO.2010.29.1567 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20567006  }} </ref> others suggest that this association is only valid when the subject has co-existing comorbidities or other cardiac risk factors.<ref name="pmid19706860">{{cite journal| author=Nanda A, Chen MH, Braccioforte MH, Moran BJ, D'Amico AV| title=Hormonal therapy use for prostate cancer and mortality in men with coronary artery disease-induced congestive heart failure or myocardial infarction. | journal=JAMA | year= 2009 | volume= 302 | issue= 8 | pages= 866-73 | pmid=19706860 | doi=10.1001/jama.2009.1137 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19706860  }} </ref>  A metanalysis of 8 randomized clinical trials of 4141 patients demonstrates that androgen suppression therapy use in [[prostate cancer]] is not significantly associated with increased cardiovascular mortality (RR=0.93; 95% CI, 0.79-1.10; P = 0.41).<ref name="pmid22147380">{{cite journal| author=Nguyen PL, Je Y, Schutz FA, Hoffman KE, Hu JC, Parekh A et al.| title=Association of androgen deprivation therapy with cardiovascular death in patients with prostate cancer: a meta-analysis of randomized trials. | journal=JAMA | year= 2011 | volume= 306 | issue= 21 | pages= 2359-66 | pmid=22147380 | doi=10.1001/jama.2011.1745 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22147380  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22508744 Review in: Ann Intern Med. 2012 Apr 17;156(8):JC4-04, JC4-05] </ref>  However, a metanalysis of 11 randomized clinical trials of 4805 patients reports that androgen suppression therapy use is associated with decreased [[prostate cancer]] related mortality (RR=0.69; 95% CI, 0.56-0.84; P < 0.001) and decreased overall mortality (RR=0.86; 95% CI, 0.80-0.93; P <0.001).<ref name="pmid22147380">{{cite journal| author=Nguyen PL, Je Y, Schutz FA, Hoffman KE, Hu JC, Parekh A et al.| title=Association of androgen deprivation therapy with cardiovascular death in patients with prostate cancer: a meta-analysis of randomized trials. | journal=JAMA | year= 2011 | volume= 306 | issue= 21 | pages= 2359-66 | pmid=22147380 | doi=10.1001/jama.2011.1745 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22147380  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22508744 Review in: Ann Intern Med. 2012 Apr 17;156(8):JC4-04, JC4-05] </ref>
 
=== Palliative care ===
[[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> 


[[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.
=== 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:
:* [[Docetaxel]]
:* [[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>


===Androgen ablation therapy===
===Other Medications===
In 1941, Charles Huggins reported that [[androgen]] ablation therapy causes regression of primary and metastatic androgen-dependent prostate cancer.<ref>Huggins C, Steven RE and Hodges CV, Studies on prostatic cancer. Arch. Sug. 43:209–223, 1941.</ref> [[Androgen]] ablation therapy causes remission in 80-90% of patients undergoing therapy, resulting in a median progression-free survival of 12 to 33 months.  After remission an androgen-independent phenotype typically emerges, where the median overall survival is 23–37 months from the time of initiation of [[androgen]] ablation therapy.<ref>Hellerstedt BA and Pienta KJ, The current state of hormonal therapy for prostate cancer, CA Cancer J. Clin. 52: 154–179, 2002.PMID 12018929</ref> The actual mechanism contributes to the progression of prostate cancer is not clear and may vary between individual patient. A few possible mechanisms have been proposed.<ref>Feldman BJ, Feldman D. The development of androgen-independent prostate cancer. Nat Rev Cancer. 2001 Oct;1(1):34–45. PMID 11900250</ref> Scientists have established a few prostate cancer cell lines to investigate the mechanism involved in the progression of prostate cancer. LNCaP, PC-3, and DU-145 are commonly used prostate cancer cell lines. The LNCaP cancer cell line was established from a human lymph node metastatic lesion of prostatic adenocarcinoma. PC-3 and DU-145 cells were established from human prostatic adenocarcinoma metastatic to bone and to brain, respectively. LNCaP cells express [[androgen receptor]] (AR), however, PC-3 and DU-145 cells express very little or no AR. AR, an androgen-activated [[transcription factor]], belongs to the steroid [[nuclear receptor]] family. Development of the prostate is dependent on androgen signaling mediated through AR, and AR is also important during the development of prostate cancer. The proliferation of LNCaP cells is [[androgen]]-dependent but the proliferation of PC-3 and DU-145 cells is [[androgen]]-insensitive.Elevation of AR expression is often observed in advanced prostate [[tumor]]s in patients.<ref>Linja MJ, Savinainen KJ, Saramaki OR, Tammela TL, Vessella RL, Visakorpi T. Amplification and overexpression of androgen receptor gene in hormone-refractory prostate cancer. Cancer Res. 2001 May 1;61(9):3550–5. PMID 11325816</ref><ref>Ford OH 3rd, Gregory CW, Kim D, Smitherman AB, Mohler JL. Androgen receptor gene amplification and protein expression in recurrent prostate cancer. J Urol. 2003 Nov;170(5):1817–21.PMID 14532783</ref> Some androgen-independent LNCaP sublines have been developed from the ATCC androgen-dependent LNCaP cells after androgen deprivation for study of prostate cancer progression. These [[androgen]]-independent LNCaP cells have elevated [[AR]] expression and express [[prostate specific antigen]] upon [[androgen]] treatment. [[Androgen]]s paradoxically inhibit the proliferation of these [[androgen]]-independent prostate [[cancer]] cells.<ref>Kokontis J, Takakura K, Hay N, Liao S. Increased androgen receptor activity and altered c-myc expression in prostate cancer cells after long-term androgen deprivation. Cancer Res. 1994 March 15;54(6):1566–73. PMID 7511045</ref><ref>Umekita Y, Hiipakka RA, Kokontis JM, Liao S. Human prostate tumor growth in athymic mice: inhibition by androgens and stimulation by finasteride. Proc Natl Acad Sci U S A. 1996 October 15;93(21):11802-7. PMID 8876218</ref><ref>Kokontis JM, Hsu S, Chuu CP, Dang M, Fukuchi J, Hiipakka RA, Liao S. Role of androgen receptor in the progression of human prostate tumor cells to androgen independence and insensitivity. Prostate. 2005 December 1;65(4):287-98. PMID 16015608</ref> [[Androgen]] at a concentration of 10-fold higher than the physiological concentration has also been shown to cause growth suppression and reversion of androgen-independent prostate cancer xenografts or androgen-independent prostate tumors derived [[in vivo]] model to an [[androgen]]-stimulated phenotype in athymic mice.<ref>Chuu CP, Hiipakka RA, Fukuchi J, Kokontis JM, Liao S. Androgen causes growth suppression and reversion of androgen-independent prostate cancer xenografts to an androgen-stimulated phenotype in athymic mice. Cancer Res. 2005 March 15;65(6):2082–4. PMID 15781616 </ref><ref>Chuu CP, Hiipakka RA, Kokontis JM, Fukuchi J, Chen RY, Liao S. Inhibition of tumor growth and progression of LNCaP prostate cancer cells in athymic mice by androgen and liver X receptor agonist. Cancer Res. 2006 July 1;66(13):6482–6. PMID 16818617</ref> These observation suggest the possibility to use androgen to treat the development of relapsed androgen-independent prostate tumors in patients. Oral infusion of [[green tea]] [[polyphenols]], a potential alternative therapy for prostate cancer by natural compounds, has been shown to inhibit the development, progression, and [[metastasis]] as well in autochthonous transgenic adenocarcinoma of the mouse prostate (TRAMP) model, which spontaneously develops prostate cancer.<ref>Gupta S, Hastak K, Ahmad N, Lewin JS, Mukhtar H. Inhibition of prostate carcinogenesis in TRAMP mice by oral infusion of green tea polyphenols. Proc Natl Acad Sci U S A. 2001 August 28;98(18):10350-5. PMID 11504910</ref>
* [[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]].


==References==
==References==
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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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