Editing Prostate cancer (section)

== Management ==
{{Main|Management of prostate cancer}}
Treatment of prostate cancer varies based on how advanced the cancer is, the risk it may spread, and the affected person's health and personal preferences.{{sfn|Rebello|Oing|Knudsen|Loeb|2021|loc="Management"}} Those with localized disease at low risk for spread are often more likely to be harmed by the side effects of treatment than the disease itself, and so are regularly tested for a worsening of their disease.{{sfn|Scher|Eastham|2022|loc="Active surveillance"}} Those at higher risk may receive treatment to eliminate the tumor – typically [[prostatectomy]] (surgery to remove the prostate) or [[radiation therapy]], sometimes alongside [[hormone therapy]].<ref name=ACSTreat>{{cite web |url=https://www.cancer.org/cancer/types/prostate-cancer/treating/by-stage.html |access-date=28 May 2023 |title=Initial Treatment of Prostate Cancer, by Stage and Risk Group |publisher=American Cancer Society |date=9 August 2022 |archive-date=28 May 2023 |archive-url=https://web.archive.org/web/20230528155727/https://www.cancer.org/cancer/types/prostate-cancer/treating/by-stage.html |url-status=live }}</ref> Those with metastatic disease are treated with [[chemotherapy]], as well as radiation or other agents to alleviate the symptoms of metastatic tumors.<ref name=ACSTreat/> Blood PSA levels are monitored every few months to assess the effectiveness of treatments, and whether the disease is recurring or advancing.<ref>{{cite web |url=https://www.cancer.org/cancer/types/prostate-cancer/treating/psa-levels-after-treatment.html |title=Following PSA Levels During and After Prostate Cancer Treatment |access-date=28 May 2023 |publisher=American Cancer Society |date=1 August 2019 |archive-date=28 May 2023 |archive-url=https://web.archive.org/web/20230528155727/https://www.cancer.org/cancer/types/prostate-cancer/treating/psa-levels-after-treatment.html |url-status=live }}</ref>

=== Localized disease ===
[[File:External beam radiotherapy NCI.jpg|thumb|alt=A person lays on a table under a large machine.|Setup for radiation therapy. The person lies flat while a radiation beam is focused on the tumor site.]]
Men diagnosed with low-risk cases of prostate cancer often defer treatment and are monitored regularly for cancer progression by [[active surveillance of prostate cancer|active surveillance]], which involves testing for tumor growth at fixed intervals by PSA tests (around every six months), digital rectal exam (annually), and MRI or repeat biopsies (every one to three years).<ref>{{cite web |url=https://www.cancer.org/cancer/types/prostate-cancer/treating/watchful-waiting.html |accessdate=16 April 2024 |title=Observation or Active Surveillance for Prostate Cancer |publisher=American Cancer Society |date=22 November 2023 |archive-date=16 April 2024 |archive-url=https://web.archive.org/web/20240416172559/https://www.cancer.org/cancer/types/prostate-cancer/treating/watchful-waiting.html |url-status=live }}</ref> This program continues until increases in PSA levels, Gleason grade, or tumor size indicate a higher-risk tumor that may require intervention.{{sfn|Liu|Patel|Haney|Epstein|2021|loc="Reclassification and progression"}} At least half of men remain on active surveillance, never requiring more direct treatment for their prostate tumors.{{sfn|Liu|Patel|Haney|Epstein|2021|loc="Abstract"}}

Those who elect to have therapy receive [[radiation therapy]] or a [[prostatectomy]]; these have similar rates of cancer control, but different side effects.{{sfn|Rebello|Oing|Knudsen|Loeb|2021|loc="Localized Disease"}}{{sfn|Scher|Eastham|2022|loc="Clinically localized prostate cancer"}} Radiation can be delivered by [[Radiation therapy#Intensity-modulated radiation therapy (IMRT)|intensity-modulated radiation therapy]] (IMRT), which allows for high doses (greater than 80 [[Gray (unit)|Gy]]) to be delivered to the prostate with relatively little radiation to other organs, or by [[brachytherapy]], where a radioactive source is surgically inserted into the prostate.{{sfn|Scher|Eastham|2022|loc="External beam radiation therapy"}}{{sfn|Scher|Eastham|2022|loc="Brachytherapy"}} IMRT is given over several sessions, with treatments repeated five days per week for several weeks. Brachytherapy is typically performed in a single session, with the radioactive source permanently implanted into the prostate, where it expends its radioactivity within the next few months.<ref>{{cite web |url=https://www.cancer.org/cancer/types/prostate-cancer/treating/radiation-therapy.html |accessdate=5 December 2023 |title=Radiation Therapy for Prostate Cancer |publisher=American Cancer Society |date=13 February 2023 |archive-date=5 December 2023 |archive-url=https://web.archive.org/web/20231205211228/https://www.cancer.org/cancer/types/prostate-cancer/treating/radiation-therapy.html |url-status=live }}</ref> With either technique, radiation damage to nearby organs can increase the risk of subsequent [[bladder cancer]] and cause [[erectile dysfunction]], [[infertility]], [[Radiation-induced lumbar plexopathy|irreversible lumbar plexopathy]]<ref>{{cite journal |last1=Brejt |first1=Nick |last2=Berry |first2=Jonathan |last3=Nisbet |first3=Angus |last4=Bloomfield |first4=David |last5=Burkill |first5=Guy |title=Pelvic radiculopathies, lumbosacral plexopathies, and neuropathies in oncologic disease: a multidisciplinary approach to a diagnostic challenge |journal=Cancer Imaging |date=December 30, 2013 |volume=13 |issue=4 |pages=591–601 |doi=10.1102/1470-7330.2013.0052 |pmid=24433993 |pmc=3893894}}</ref> and [[radiation proctitis]] – damage to the rectum that can cause [[diarrhea]], [[blood in stool|bloody stools]], [[fecal incontinence]], and pain.{{sfn|Brawley|Mohan|Nein|2018|loc="Radiation therapy"}}

[[File:Surgeon performing robot-assisted surgery.jpg|thumb|alt=A surgeon sits with his face surrounded by a computer terminal|A surgeon performs robot-assisted surgery.]]
Radical prostatectomy aims to surgically remove the cancerous part of the prostate, along with the seminal vesicles, and the end of the [[vas deferens]] (the duct that delivers sperm from the testes).{{sfn|Dall'Era|2023|loc="Radical prostatectomy"}} In wealthier countries, this is typically done by [[robot-assisted surgery]], where robotic tools inserted through small holes in the abdomen allow a surgeon to make small and exact movements during surgery.{{sfn|Costello|2020|loc="The rise of robotic surgery"}} This method results in shorter hospital stays, less blood loss, and fewer complications than traditional open surgery.{{sfn|Costello|2020|loc="The rise of robotic surgery"}} In places where robot-assisted surgery is unavailable, prostatectomy can be performed [[laparoscopy|laparoscopically]] (using a camera and hand tools through small holes in the abdomen), or through traditional open surgery with an incision above the penis (retropubic approach) or below the scrotum (perineal approach).{{sfn|Scher|Eastham|2022|loc="Radical prostatectomy"}}{{sfn|Costello|2020|loc="The rise of robotic surgery"}} The four approaches result in similar rates of cancer control.{{sfn|Scher|Eastham|2022|loc="Radical prostatectomy"}} Damage to nearby tissue during surgery can result in erectile dysfunction and [[urinary incontinence]]. Erectile dysfunction is more likely in those who are older or had previous erectile issues.{{sfn|Scher|Eastham|2022|loc="Radical prostatectomy"}} Incontinence is more common in those who are older and have shorter [[urethra]]s.{{sfn|Scher|Eastham|2022|loc="Radical prostatectomy"}} Both for cancer progression outcomes and surgical side effects, the skill and experience of the individual surgeon doing the procedure are among the greatest determinants of success.{{sfn|Scher|Eastham|2022|loc="Radical prostatectomy"}}

After prostatectomy, PSA levels drop rapidly, reaching very low or undetectable levels within two months. Radiotherapy also substantially reduces PSA levels, but more slowly and less completely, with PSA levels reaching their nadir two years after radiotherapy.<ref>{{cite web |url=https://www.cancer.org/cancer/types/prostate-cancer/treating/psa-levels-after-treatment.html |accessdate=5 December 2023 |title=Following PSA Levels During and After Prostate Cancer Treatment |publisher=American Cancer Society |date=1 August 2019 |archive-date=7 December 2023 |archive-url=https://web.archive.org/web/20231207065408/https://www.cancer.org/cancer/types/prostate-cancer/treating/psa-levels-after-treatment.html |url-status=live }}</ref> After either treatment, PSA levels are  monitored regularly. Up to half of those treated will eventually have a rise in PSA levels, suggesting the tumor or small metastases are growing again.{{sfn|Rebello|Oing|Knudsen|Loeb|2021|loc="Biochemical recurrence and residual disease"}} People with high or rising PSA levels are often offered another round of radiation therapy directed at the former tumor site. This reduces risk for further progression by 75%.{{sfn|Rebello|Oing|Knudsen|Loeb|2021|loc="Biocehmical recurrence and residual disease"}} Those suspected of metastases can undergo PET scanning with sensitive [[PET radiotracer|radiotracers]] C-11 choline, F-18 fluciclovine, and F-18 or Ga-68 attached to a PSMA-targeting drug, each of which is able to detect small metastases more sensitively than alternative imaging methods.{{sfn|Scher|Eastham|2022|loc="Rising PSA after definitive local therapy"}}{{sfn|Rebello|Oing|Knudsen|Loeb|2021|loc="Biocehmical recurrence and residual disease"}}

=== Metastatic disease ===
[[File:Verlauf Prostatakrebs 2011-01 Posttherapie-Szintigramm cropped.jpg|thumb|Bone scintigraphy scan of a man with metastatic prostate cancer. Dark spots indicate metastases along the pelvis, ribs, and shoulder. |alt=Medical image showing a man's skeleton with several dark spots along the bones.]]
For those with metastatic disease, the standard of care is [[androgen deprivation therapy]] (also called "chemical castration"), drugs that reduce levels of [[androgen]]s (male sex hormones) that prostate cells require to grow.{{sfn|Rebello|Oing|Knudsen|Loeb|2021|loc="Metastatic hormone-sensitive prostate cancer"}} Various drugs are used to lower androgen levels by blocking the synthesis or action of [[testosterone]], the primary androgen. The first line of treatment typically involves [[Gonadotropin-releasing hormone agonist|GnRH agonist]]s like [[leuprolide]], [[goserelin]], or [[triptorelin]] by injection monthly or less frequently as needed.<ref>{{cite web |url=https://www.cancer.org/cancer/types/prostate-cancer/treating/hormone-therapy.html |access-date=15 May 2023 |title=Hormone Therapy for Prostate Cancer |date=9 August 2022 |publisher=American Cancer Society |archive-date=15 May 2023 |archive-url=https://web.archive.org/web/20230515212541/https://www.cancer.org/cancer/types/prostate-cancer/treating/hormone-therapy.html |url-status=live }}</ref>{{sfn|Rebello|Oing|Knudsen|Loeb|2021|loc="Metastatic hormone-sensitive prostate cancer"}} GnRH agonists cause a brief rise in testosterone levels at treatment initiation, which can worsen disease in people with significant symptoms of metastases.{{sfn|Scher|Eastham|2022|loc="Testosterone-lowering agents"}} In these people, [[Gonadotropin-releasing hormone antagonist|GnRH antagonists]] like [[degarelix]] or [[relugolix]] are given instead, and can also rapidly reduce testosterone levels.{{sfn|Scher|Eastham|2022|loc="Testosterone-lowering agents"}} Reducing testosterone can cause various side effects, including [[hot flash]]es, reduction in muscle mass and bone density, reduced sex drive, fatigue, personality changes, and an increased risk of diabetes, cardiovascular disease, and depression.{{sfn|Scher|Eastham|2022|loc="Testosterone-lowering agents"}} Hormone therapy halts tumor growth in more than 95% of those treated,{{sfn|Achard|Putora|Omlin|Zilli|2022|loc="Introduction"}} and PSA levels return to normal in up to 70%.{{sfn|Scher|Eastham|2022|loc="Outcomes of androgen deprivation"}}

Despite reduced testosterone levels, metastatic prostate tumors eventually continue to grow – manifested by rising blood PSA levels, and metastases to nearby bones.{{sfn|Scher|Eastham|2022|loc="Metastatic disease: castrate"}}{{sfn|Rebello|Oing|Knudsen|Loeb|2021|loc="Metastatic castration-resistant prostate cancer"}} This is the most advanced stage of the disease, called castration-resistant prostate cancer (CRPC). CRPC tumors continuously evolve resistance to treatments, necessitating several lines of therapy, each used in sequence to extend survival. The standard of care is the chemotherapy [[docetaxel]] along with [[antiandrogen]] drugs, namely the androgen receptor antagonists [[enzalutamide]], [[apalutamide]], and [[darolutamide]], as well as the testosterone production inhibitor [[abiraterone acetate]].{{sfn|Teo|Rathkopf|Kantoff|2019|loc="Management of metastatic castration-resistant prostate cancer"}}{{sfn|Scher|Eastham|2022|loc="Metastatic disease: castrate"}}{{sfn|Teo|Rathkopf|Kantoff|2019|loc="Abiraterone acetate"}} An alternative is the [[Cancer immunotherapy#Cellular immunotherapy|cell therapy]] procedure [[Sipuleucel-T]], where the affected person's immune cells are removed, treated to more effectively target prostate cancer cells, and re-injected.{{sfn|Scher|Eastham|2022|loc="Metastatic disease: castrate"}} Tumors that evolve resistance to docetaxel may receive the second-generation [[taxane]] drug [[cabazitaxel]].{{sfn|Scher|Eastham|2022|loc="Metastatic disease: castrate"}}

Some CRPC treatments are used only in men whose tumors have certain characteristics that make the therapy more likely to be effective. Men whose tumors express the protein [[prostate-specific membrane antigen|PSMA]] may receive the radiopharmaceutical [[Lutetium (177Lu) vipivotide tetraxetan|Lu-177 PSMA]], which binds to and destroys PSMA-positive cells.<ref>{{cite web |url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pluvicto-metastatic-castration-resistant-prostate-cancer |accessdate=9 January 2024 |title=FDA Approves Pluvicto for Metastatic Castration-Resistant Prostate Cancer |publisher=U.S. Food & Drug Administration |date=23 March 2022 |archive-date=24 March 2022 |archive-url=https://web.archive.org/web/20220324031828/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pluvicto-metastatic-castration-resistant-prostate-cancer |url-status=live }}</ref>{{sfn|Scher|Eastham|2022|loc="Metastatic disease: castrate"}} Those whose tumors have defective [[DNA damage repair]] benefit from treatment with the [[immune checkpoint inhibitor]] drug [[pembrolizumab]] and [[Poly (ADP-ribose) polymerase|PARP]] inhibitors, namely [[olaparib]], [[rucaparib]], or [[niraparib]].{{sfn|Scher|Eastham|2022|loc="Metastatic disease: castrate"}}

=== Supportive care ===

Bone metastases – present in around 85% of those with metastatic prostate cancer – are the primary cause of symptoms and death from metastatic prostate cancer.{{sfn|Coleman|Croucher|Padhani|Clézardin|2020|loc="Prevalence of bone metastases"}}{{sfn|Coleman|Croucher|Padhani|Clézardin|2020|loc="Prevalence of SREs"}} Those with constant pain are prescribed [[nonsteroidal anti-inflammatory drug]]s.{{sfn|Coleman|Croucher|Padhani|Clézardin|2020|loc="Analgesics used in CIBP"}} However, people with bone metastases can experience "breakthrough pain", sudden bursts of severe pain that resolve within around 15 minutes, before [[analgesic|pain medications]] can take effect.{{sfn|Coleman|Croucher|Padhani|Clézardin|2020|loc="Analgesics used in CIBP"}} Single sites of pain can be treated with [[external beam radiotherapy|external beam radiation therapy]] to shrink nearby tumors.{{sfn|Scher|Eastham|2022|loc="Pain management"}} More dispersed bone pain can be treated with radioactive compounds that disproportionately accumulate in bone, like [[radium-223]] and [[Samarium (153Sm) lexidronam|samarium-153-EDTMP]], which help reduce the size of bone tumors. Similarly, the systemic chemotherapeutics used for metastatic prostate cancer can reduce pain as they shrink tumors.{{sfn|Scher|Eastham|2022|loc="Pain management"}} Other bone modifying agents like [[zoledronic acid]] and [[denosumab]] can reduce prostate cancer bone pain, even though they have little effect on tumor size.{{sfn|Scher|Eastham|2022|loc="Pain management"}} Metastases compress the spinal cord in up to 12% of those with metastatic prostate cancer causing pain, weakness, numbness, and paralysis.{{sfn|Thompson|Wood|Feuer|2007|loc="Cord compression"}}<ref name=MSCC>{{cite web |url=https://prostatecanceruk.org/prostate-information-and-support/advanced-prostate-cancer/metastatic-spinal-cord-compression-mscc?scrollTo=symptoms-of-MSCC |access-date=25 June 2023 |title=What is Metastatic Spinal Cord Compression (MSCC)? |publisher=Prostate Cancer UK |date=June 2022 |archive-date=26 June 2023 |archive-url=https://web.archive.org/web/20230626033230/https://prostatecanceruk.org/prostate-information-and-support/advanced-prostate-cancer/metastatic-spinal-cord-compression-mscc?scrollTo=symptoms-of-MSCC |url-status=live }}</ref> Inflammation in the spine can be treated with high-dose steroids, as well as surgery and radiotherapy to shrink spinal tumors and relieve pressure on the spinal cord.{{sfn|Thompson|Wood|Feuer|2007|loc="Cord compression"}}<ref name=MSCC/>

Those with advanced prostate cancer suffer fatigue, lethargy, and a generalized weakness. This is caused in part by gastrointestinal problems, with [[loss of appetite]], weight loss, nausea, and [[constipation]] all common. These are typically treated with appetite-increasing drugs – [[megestrol acetate]] or corticosteroids – [[antiemetic]]s, or treatments that focus on underlying gastrointestinal issues.{{sfn|Thompson|Wood|Feuer|2007|loc="Gastrointestinal symptoms"}} General weakness can also be caused by [[anemia]], itself caused by a combination of the disease itself, poor nutrition, and damage to the bone marrow from cancer treatments or bone metastases.{{sfn|Thompson|Wood|Feuer|2007|loc="General debility"}} Anemia can be treated in various ways depending on the cause, or can be addressed directly with [[blood transfusion]]s.{{sfn|Thompson|Wood|Feuer|2007|loc="General debility"}} Organ damage and metastases in the lymph nodes can lead to uncomfortable accumulation of fluid (called [[lymphedema]]) in the genitals or lower limbs. These swellings can be extremely painful, curtailing an affected person's ability to urinate, have sex, or walk normally. Lymphedema can be treated by applying pressure to aid drainage, surgically draining pooled fluid, and cleaning and treating nearby damaged skin.{{sfn|Thompson|Wood|Feuer|2007|loc="Lymphoedema"}}

People with prostate cancer are around twice as likely to experience [[anxiety]] or [[Depression (mood)|depression]] compared to those without cancer.{{sfn|Mundle|Afenya|Agarwal|2021|loc="Estimates of anxiety, depression, and distress"}} When added to normal prostate cancer treatments, psychological interventions such as [[psychoeducation]] and [[cognitive behavioral therapy]] can help reduce anxiety, depression, and general distress.{{sfn|Mundle|Afenya|Agarwal|2021|loc="Abstract"}}

As those severely ill with metastatic prostate cancer approach the end of their lives, most experience confusion and may [[hallucinate]] or have trouble recognizing loved ones.{{sfn|Thompson|Wood|Feuer|2007|loc="Delirium"}}<ref name=PCUK>{{cite web|url=https://prostatecanceruk.org/prostate-information-and-support/advanced-prostate-cancer/dying-from-prostate-cancer/what-to-expect |access-date= 25 June 2023 |title=Dying from Prostate Cancer – What to Expect |publisher=Prostate Cancer UK |date=July 2018}}</ref> Confusion is caused by various conditions, including [[kidney failure]], [[sepsis]], [[dehydration]], and as a side effect of various drugs, especially [[opioid]]s.{{sfn|Thompson|Wood|Feuer|2007|loc="Delirium"}} Most people sleep for long periods, and some feel drowsy when awake.<ref name=PCUK/> Restlessness is also common, sometimes caused by physical discomfort from constipation or [[urinary retention]], sometimes caused by anxiety.<ref name=PCUK/> In their last few days, affected men's breathing may become shallow and slow, with long pauses between breaths. Breathing may be accompanied by a [[terminal secretions|rattling noise]] as fluid lingers in the throat, but this is not uncomfortable for the affected person.<ref name=PCUK/><ref name=ASCO>{{cite web |url=https://www.cancer.net/navigating-cancer-care/advanced-cancer/care-through-final-days |access-date=25 June 2023 |title=Care Through the Final Days |date=November 2022 |publisher=American Society of Clinical Oncology |archive-date=26 June 2023 |archive-url=https://web.archive.org/web/20230626033230/https://www.cancer.net/navigating-cancer-care/advanced-cancer/care-through-final-days |url-status=live }}</ref> Their hands and feet may cool to the touch, and skin become blotchy or blue due to weaker blood circulation. Many stop eating and drinking, resulting in dry-feeling mouth, which can be aided by moistening the mouth and lips.<ref name=PCUK/> The person becomes less and less responsive, and eventually the heart and breathing stop.<ref name=ASCO/>