Prostate Cancer

Epidemiology and Etiology

Prostate cancer is the most common cancer in men in the US, with an estimated 191,330 new cases and 33,330 deaths in 2020.1 Common risk factors include advanced age, family history, and ethnicity, with higher incidences in African-Americans and lower incidence in Asians. In the US, the lifetime risk of being diagnosed with prostate cancer is approximately 11%, whereas the risk of dying from prostate cancer is 2.5%.

Pathology

Adenocarcinoma is the most common histology.

Screening

Although screening may be associated with a modest decrease in the probability of death from prostate cancer, it may be also be associated with harms including false-positive tests leading to prostate biopsy with its associated complications, overdiagnosis, and overtreatment. Therefore, the 2018 USPSTF guidelines recommend that the decision regarding PSA-based screening for prostate cancer in men aged 55–69 years should be individualized after an informed discussion with the patient regarding the potential benefits and harms.2

Clinical Presentation

The most common presentation in the US is asymptomatic elevation in PSA. Digital rectal examination (DRE) of the prostate may demonstrate asymmetric induration or nodules. Obstructive symptoms, new-onset erectile dysfunction, hematuria, or hematospermia are less common. Bone is the most common site of metastatic involvement, and patients with skeletal metastases can present with pain, fractures, or nerve root compression.

Diagnostic Testing

The diagnosis of prostate cancer is usually made through transrectal ultrasonography-guided biopsy, although MRI-guided biopsies may also be used. PSA levels should be obtained. Bone scan and CT of the abdomen and pelvis are recommended for patients with high-risk disease and select patients with intermediate-risk disease. PSMA PET CT imaging increases the rate of detection of metastases to pelvic lymph nodes or occult distant sites.

Staging

Based on TNM classification, early stage disease (T1–T2) is confined to the prostate, locally advanced disease (T3–T4) is defined by local invasion outside the prostate, and stage IV disease is defined by nodal involvement (N1) and/or metastatic disease (M1). Further risk classification of prostate cancer is based on PSA, stage, and Gleason score (GS), with the latter representing the summation of the most prominent and second most prominent Gleason patterns, each ranging from 1 to 5 and added together to give a GS of low (≤6), intermediate (7), or high (>7). This classification may be converted into the International Society of Urological Pathology (ISUP) groups which include group 1 (GS ≤6), group 2 (GS 3 + 4 = 7), group 3 (GS 4 + 3 = 7), group 4 (GS 8), and group 5 (GS ≥9). Patients are then classified as very low risk (PSA<10 ng/mL, group 1, nonpalpable tumor identified on biopsy alone [T1c or less], and <3 biopsy cores positive and <50% cancer/core), low risk (PSA <10, group 1, and tumor involving no more than one half of one side of the prostate [T2a]), intermediate risk (PSA 10–20, group 2 or 3, or tumor involving up to both sides of prostate [T2c or less]), high risk (PSA >20, group >3 or extraprostatic spread [T3a]), and very high risk (primary Gleason pattern 5, >4 cores of group 4 or 5, invades seminal vesicles and/or other adjacent structures [T3b–T4], multiple high-risk features).3

Treatment

  • Patients with clinically localized disease (stage T1 or T2) may be managed with surveillance, radiation therapy (external beam radiation or brachytherapy), or surgery. Specifically, for patients with very-low-risk disease and expected survival >10 years, active surveillance is the preferred option. Patients with low-risk disease and >10 years life-expectancy may be considered for active surveillance, radiation therapy, or surgery. Patients with intermediate- or high-risk disease should be treated with radical prostatectomy plus pelvic lymph node dissection or radiation therapy (external beam radiation or brachytherapy) with or without androgen deprivation therapy (ADT). Docetaxel may be added to radiotherapy plus ADT in patients with high-risk disease. ADT includes surgical orchiectomy or medical castration with a gonadotropin-releasing hormone (GnRH) agonist (leuprolide or goserelin) or antagonist (degarelix).
  • Metastatic disease may be treated with ADT in combination with docetaxel or an AR signaling inhibitor (abiraterone/prednisone, enzalutamide, or apalutamide). Patients with castration-resistant disease may be treated with docetaxel or cabazitaxel. Other options for subsequent therapy include ICIs, the autologous cellular therapy sipuleucel-T, Radium-223, and PARP inhibitors for patients with BRCA1, BRCA2, or ATM mutations.3

References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7-30.  [PMID:31912902]
  2. US Preventive Services Task Force, Grossman DC, Curry SJ, et al. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. J Am Med Assoc. 2018;319(18):1901.
  3. Rebello RJ, Oing C, Knudsen KE, et al. Prostate cancer. Nat Rev Dis Primers. 2021;7(1):9.  [PMID:33542230]

Outline


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