STAGES OF PROSTATE CANCER

The TNM system is the standardized method for classifying the extent of prostate cancer progression. This classification evaluates three key components: [5][26]

T (Tumor): Indicates the size and local extent of the primary tumor within or beyond the prostate, ranging from a - the smallest, to c - the largest.
N (Nodes): Specifies whether cancer has spread to regional lymph nodes.
M (Metastasis): Determines if distant metastasis to other organs has occurred. [26]

This system provides a more precise framework for characterizing prostate cancer, enabling clinicians to assess disease severity, guide treatment decisions, and evaluate prognosis with greater accuracy than numbered staging (stages I - IV) alone. [26]

[8]

T1 : The Hidden Cancer
(Tumor Can't Be Felt or Seen on Imaging)

T1-a

Found accidentally during surgery for BPH (benign prostate enlargement)

Prostate specific antigen-producing cells start overproducing PSA (sometimes as irregular isoforms) [5]

<5% of tissue has cancer

T1-b

Increased atypia alongside early disruption of the basal cell layer.

Early androgen receptor (AR) mutations begin. [4][5]

Tumor remains non-palpable/non-visible on imaging, however, >5% of tissue has cancer

T1-c

KLK3 gene (which makes the PSA protein) overexpression independent of androgen stimulation masks tumor presence from immune surveillance. [22]

The elevated PSA results may warrant a targeted needle biopsy of suspicious areas [4][22]

T2 : The Contained Cancer
(Tumor Confined to Prostate But Can Be Felt/Seen)

T2-a

Tumor is now large enough to feel

Bcl-2 protein blocks cell death. [22][5]

Microvascular proliferation follows (tiny new blood vessels feed the tumor).

DRE (finger exam) feels a small, hard nodule confirmed by biopsy.

Tumor in ≤50% of one prostate lobe

T2-b

mTOR (a kinase) pathway is hijacked which makes cells grow uncontrollably. [22]

PTEN gene loss removes a critical "brake" on cancer development. [5]

Larger lump felt on DRE + MRI shows dark mass in one lobe.

Tumor now fills >50% of one lobe but hasn’t crossed the midline.

T2-c

Inflammatory stroma (tumor recruits "helper" cells).

MMP-2 enzyme is secreted by the tumor to start softening surrounding tissue.

Abnormal DRE on both sides + MRI shows bilateral lesions.

Tumor now in both left and right prostate lobes. [4][22]

[25]

T3 : The Escaped Cancer
(Tumor Breaks Through Prostate Capsule)

T3-a

The tumor has grown large enough to break through the prostate’s outer shell (capsule)

TGF-β secretion signals nearby fibroblasts to "help" the tumor grow.

E-cadherin loss: cancer cells detach easily, allowing them to escape into surrounding tissue.

E-cadherin acts like "cellular glue", keeping prostate cells stuck together. [5][22]

MRI shows ragged, irregular edges where cancer is leaking out, this is confirmed by biopsy showing cancer eyond prostate capsule

T3-b

!High risk of metastasis!

The cancer has now spread to the seminal vesicles (two small pouches behind the prostate that store semen).

A mutated version of the androgen receptor (AR) appears, making the cancer resist hormone therapy.

This turns treatments like Lupron or abiraterone less effective. [5][22]

MRI shows tumor extending into the seminal vesicles, this is confirmed by biopsy.

T4 : The Invasive Cancer
(Tumor Invades Neighboring Organs)

T4-a

The cancer has now invaded nearby bladder (front) or rectum (back)

Cathepsin D (strong digestive enzyme)is released by cancer cells that:

Breaks down collagen and other structural proteins in healthy tissue.
Creates space for the tumor to expand into bladder/rectal walls.

Upregulated PD-L1 Binds to immune cells (T-cells) and shuts them down, effectvely making the tumor grow undetected by the immune system. [5][22][17]

MRI shows tumor eroding into bladder/rectal walls.

Symptoms: Blood in urine (hematuria) or stool (hematochezia), painful urination/bowel movements.

T4-b

The cancer has now anchored itself to pelvic bones or muscles, making it inoperable.

PTHrP secretion (Parathyroid Hormone-related Protein)

signals the body into over-activating osteoclasts (bone-eating cells), causing:

Lytic bone lesions (holes in bones, visible on scans).
Hypercalcemia (dangerously high blood calcium levels).
Severe bone pain [4][5]

BRCA2 mutations observed in late stage prostate cancer

disrupt DNA repair mechanisms, leading to:

Faster accumulation of new mutations.
Resistance to radiation and chemotherapy.
Increased risk of metastasis to distant sites [5]

PSMA-PET/ CAT scans pinpoint exact locations of bone/pelvic involvement.

N1: The "Lymph Node Invasion" Stage

Cancer cells have now escaped the prostate area entirely, traveling through lymphatic channels to pelvic lymph nodes [5]