Editing Prostate cancer (section)

== Diagnosis ==
[[File:Digital rectal exam nci-vol-7136-300.jpg|left|thumb|Diagram of a digital rectal exam |alt=A gloved finger inserted into a man's rectum presses on the prostate]]

Men suspected of having prostate cancer may undergo several tests to assess the prostate. One common procedure is the [[rectal examination|digital rectal examination]], in which a doctor inserts a lubricated finger into the [[rectum]] to feel the nearby prostate.<ref>{{cite web |url=https://www.cancer.org/cancer/types/prostate-cancer/detection-diagnosis-staging/how-diagnosed.html |access-date=18 May 2023 |title=Tests to Diagnose and Stage Prostate Cancer |publisher=American Cancer Society |date=21 February 2023 |archive-date=18 May 2023 |archive-url=https://web.archive.org/web/20230518160203/https://www.cancer.org/cancer/types/prostate-cancer/detection-diagnosis-staging/how-diagnosed.html |url-status=live }}</ref>{{sfn|Rebello|Oing|Knudsen|Loeb|2021|loc="Diagnosis"}} Tumors feel like stiff, irregularly shaped lumps against the rest of the prostate. Hardening of the prostate can also be due to [[benign prostatic hyperplasia]]; around 20–25% of those with abnormal findings on their rectal exams have prostate cancer.{{sfn|Scher|Eastham|2022|loc="Physical examination"}} Several urological societies' guidelines recommend [[magnetic resonance imaging]] (MRI) to evaluate the prostate for potential tumors in men with high PSA levels. MRI results can help distinguish those who have potentially dangerous tumors from those who do not.{{sfn|Maffei|Giganti|Moore|2023|loc="MRI as a test for clinically referred men with a raised PSA or abnormal digital rectal exam}}

A definitive diagnosis of prostate cancer requires a [[biopsy]] of the prostate. Prostate biopsies are typically taken by a needle passing through the rectum or [[Transperineal biopsy|perineum]], guided by [[transrectal ultrasonography]], MRI, or a combination of the two.{{sfn|Scher|Eastham|2022|loc="Prostate biopsy"}}{{sfn|Rebello|Oing|Knudsen|Loeb|2021|loc="Diagnosis"}} Ten to twelve samples are taken from several regions of the prostate to improve the chances of finding any tumors.{{sfn|Rebello|Oing|Knudsen|Loeb|2021|loc="Diagnosis"}} Biopsies are sent for a [[histopathologic diagnosis of prostate cancer]], wherein they are examined under a microscope by a [[pathology|pathologist]], who determines the type and extent of cancerous cells present. Cancers are first classified based on their appearance under a microscope. Over 95% of prostate cancers are classified as [[adenocarcinoma]]s (resembling [[gland]] tissue), with the rest largely [[squamous-cell carcinoma]] (resembling [[squamous cell]]s, a type of [[epithelial cell]]) and [[transitional cell carcinoma]] (resembling [[transitional cell]]s).{{sfn|Scher|Eastham|2022|loc="Pathology"}}

[[File:Gallium PSMA PET scan.png|thumb|[[CT scan]] (left) and [[PSMA scan]] (right) showing prostate cancer metastases in the bone (red arrows). The dye used for PSMA scans is also absorbed by the kidneys, liver, and spleen (large dark objects at right). |alt=Medical images of a man's torso. Arrows indicate tumor metastases, visible as dots in the man's spine and pelvis, in both scans.]]

Next, tumor samples are [[Grading (tumors)|graded]] based on how much the tumor tissue differs from normal prostate tissue; the more different the tumor appears, the faster the tumor is likely to grow. The [[Gleason grading system]] is commonly used, where the pathologist assigns numbers ranging from 3 (most similar to healthy prostate tissue) to 5 (least similar) to different regions of the biopsied tissue. They then calculate a "Gleason score" by adding the two numbers that represent the largest areas of the biopsy sample.{{sfn|Scher|Eastham|2022|loc="Pathology"}} The lowest possible Gleason score of 6 represents a biopsy most similar to healthy prostate; the highest Gleason score of 10 represents the most severely cancerous.{{efn|group=note|The original 1966 Gleason grading system allowed pathologist scores of 1 to 5, resulting in Gleason scores of 2 to 10; however, a 2005 update by the [[International Society of Urological Pathology]] largely eliminated the pathologist scores 1 and 2. In common practice, tumors are now scored 3 to 5, resulting in Gleason scores of 6 to 10.{{sfn|Epstein|2018|loc="Historical background", "2005 and 2014 ISUP grading conferences", and "Gleason patterns"}}}} Gleason scores are commonly grouped into "Gleason grade groups", which predict disease prognosis: a Gleason score of 6 is Gleason grade group 1 (best prognosis). A score of 7 (with Gleason scores 4 + 3, or Gleason scores 3 + 4, with the most prominent listed first) can be grade group 2 or 3; it is grade group 2 if the less severe Gleason score (3) covered more area; grade group 3 if the more severe Gleason score (4) covered more area. A score of 8 is grade group 4. A score of 9 or 10 is grade group 5 (worst prognosis).{{sfn|Scher|Eastham|2022|loc="Pathology"}}

The extent of cancer spread is assessed by MRI or [[PSMA scan]] – a [[positron emission tomography]] (PET) imaging technique where a [[radiopharmaceutical|radioactive label]] that binds the prostate protein [[prostate-specific membrane antigen]] is used to detect metastases distant from the prostate.{{sfn|Scher|Eastham|2022|loc="Prostate cancer staging"}}{{sfn|Rebello|Oing|Knudsen|Loeb|2021|loc="Diagnosis"}} [[CT scan]]s may also be used, but are less able to detect spread outside the prostate than MRI. [[Bone scintigraphy]] is used to test for spread of cancer to bones.{{sfn|Scher|Eastham|2022|loc="Prostate cancer staging"}}

=== Staging ===
{{Main|Prostate cancer staging}}
[[File:Diagram showing T1-3 stages of prostate cancer CRUK 278.svg|thumb|left|Diagram showing T1 to T3 stages of prostate cancer |alt=Diagram of a prostate showing a small (T1), medium (T2), and large (T3) tumor.]]

After diagnosis, the tumor is [[cancer staging|staged]] to determine the extent of its growth and spread. Prostate cancer is typically staged using the [[American Joint Committee on Cancer]]'s (AJCC) three-component [[TNM staging system|TNM system]], with scores assigned for the extent of the tumor (T), spread to any lymph nodes (N), and the presence of [[metastases]] (M).<ref name=ACSStage>{{cite web |url=https://www.cancer.org/cancer/types/prostate-cancer/detection-diagnosis-staging/staging.html |title=Prostate Cancer Staging |date=8 October 2021 |publisher=American Cancer Society |access-date=14 May 2023 |archive-date=15 May 2023 |archive-url=https://web.archive.org/web/20230515034626/https://www.cancer.org/cancer/types/prostate-cancer/detection-diagnosis-staging/staging.html |url-status=live }}</ref> Scores of T1 and T2 represent tumors that remain within the prostate: T1 is for tumors not detectable by imaging or digital rectal exam; T2 is for tumors detectable by imaging or rectal exam, but still confined within the prostate.{{sfn|Scher|Eastham|2022|loc="Table 87-1 TNM classification"}} T3 is for tumors that grow beyond the prostate – T3a for tumors with any extension outside the prostate; T3b for tumors that invade the adjacent [[seminal vesicle]]s. T4 is for tumors that have grown into organs beyond the seminal vesicles.{{sfn|Scher|Eastham|2022|loc="Table 87-1 TNM classification"}} The N and M scores are binary (yes or no). N1 represents any spread to the nearby lymph nodes. M1 represents any metastases to other body sites.{{sfn|Scher|Eastham|2022|loc="Table 87-1 TNM classification"}}

The AJCC then combines the TNM scores, Gleason grade group, and results of the PSA blood test to categorize cancer cases into one of four stages, and their subdivisions. Cancer cases with localized tumors (T1 or T2), no spread (N0 and M0), Gleason grade group 1, and PSA less than 10&nbsp;ng/mL are designated stage I. Those with localized tumors and PSA between 10 and 20&nbsp;ng/mL are designated stage II – subdivided into IIA for Gleason grade group 1, IIB for grade group 2, and IIC for grade group 3 or 4. Stage III is the designation for any of three higher risk factors: IIIA is for a PSA level about 20&nbsp;ng/mL; IIIB is for T3 or T4 tumors; IIIC is for a Gleason grade group of 5. Stage IV is for cancers that have spread to lymph nodes (N1, stage IVA) or other organs (M1, stage IVB).<ref name=ACSStage/>
{| class="wikitable floatright" style="text-align:center;font-size:90%;margin-left:1em;"
|+AJCC stage for prostate cancer
!AJCC Stage
!TNM scores
!Gleason grade group
!PSA
|-
|Stage I
|T1 or T2, N0, M0
|1
|<10&nbsp;ng/mL
|-
|Stage IIA
| rowspan="3" |T1 or T2, N0, M0
|1
| rowspan="3" |10-20&nbsp;ng/mL
|-
|Stage IIB
|2
|-
|Stage IIC
|3 or 4
|-
|Stage IIIA
|T1 or T2, N0, M0
| rowspan="2" |3 or 4
|> 20&nbsp;ng/mL
|-
|Stage IIIB
|T3 or T3, N0, M0
| rowspan="2" |10–20&nbsp;ng/mL
|-
|Stage IIIC
|T1 or T2, N0, M0
|5
|-
|Stage IVA
|Any T, N1
| rowspan="2" |Any group
| rowspan="2" |Any PSA
|-
|Stage IVB
|Any T, M1
|}

The United Kingdom [[National Institute for Health and Care Excellence]] recommends a five-stage system based on disease prognosis called the Cambridge Prognostic Group, with prognostic groups CPG&nbsp;1 to CPG&nbsp;5.<ref name=":2">{{cite web |title=Prostate Cancer: Diagnosis and Management. NICE Guideline [NG131] |url=https://www.nice.org.uk/guidance/ng131/chapter/Recommendations#assessment-and-diagnosis |access-date=3 October 2022 |website=National Institute for Health and Care Excellence (NICE) |date=9 May 2019 |archive-date=11 August 2023 |archive-url=https://web.archive.org/web/20230811131224/https://www.nice.org.uk/guidance/ng131/chapter/Recommendations#assessment-and-diagnosis |url-status=live }}</ref> CPG&nbsp;1 is the same as AJCC stage I. Cases with localized tumors (T1 or T2) and either Gleason grade group 2 or higher PSA levels (10 to 20&nbsp;ng/mL) are designated CPG&nbsp;2. CPG&nbsp;3 represents either Gleason grade group 3, or the combination of the CPG&nbsp;2 criteria. CPG&nbsp;4 is similar to AJCC stage 3 – any of Gleason grade group 4, PSA levels above 20&nbsp;ng/mL, or a tumor that has grown beyond the prostate (T3). CPG&nbsp;5 is for the highest risk cases: either a T4 tumor, Gleason grade group 5, or any two of the CPG&nbsp;4 criteria.<ref>{{cite web |url=https://www.cancerresearchuk.org/about-cancer/prostate-cancer/stages/cambridge-prognostic-group-cpg |access-date=25 June 2023 |title=Prostate Cancer Risk Groups and the Cambridge Prognostic Group (CPG) |publisher=Cancer Research UK |date=24 May 2022 |archive-date=11 August 2023 |archive-url=https://web.archive.org/web/20230811132255/https://www.cancerresearchuk.org/about-cancer/prostate-cancer/stages/cambridge-prognostic-group-cpg |url-status=live }}</ref>