Gurdarshan S. Sandhu, MD
Gerald L. Andriole, MD, FACS
BASICS
DESCRIPTION
• A prostatenadule is usually described as a palpable lesion detected on digital rectal exam (DRE) raise concern for prostate cancer (CaP)
• Nodules can be described as soft, rubbery, firm, hard, or rock hard
• Nodules can be well circumscribed or irregular and diffuse
• A normal prostate is about the size of a chestnut and has a consistency similar to that of the contracted thenar eminence of the thumb.
– This can be simulated by opposing the thumb to the little finger and palpating the contracted muscle
• Consistency of nodule can denote underlying pathology.
• Rapidity of appearance and changes in size and consistency can infer malignant potential.
• Nodule detection by DRE is recommended as part of prostate cancer detection programs.
– Current recommendations from the American Cancer Society are, if men decides to be tested for prostate cancer, they should have the PSA blood test with or without a rectal exam.
EPIDEMIOLOGY
Incidence
• Prostate nodule as an isolated finding with normal PSA is found in <10% of cases of prostate cancer in the US
• Increasingly men are being diagnosed with prostate cancer based on an elevated serum prostate-specific antigen (PSA) and not an abnormal DRE (50% of diagnoses in 2002) (1)
• 94% of men diagnosed with prostate cancer in 2004–2005 have localized disease (cT1 or cT2) (2)
Prevalence
5–10% of men in screening programs have abnormal/suspicious DRE
RISK FACTORS
• Prostate cancer
– Nodule that changes in consistency and size over time
– Elevated serum PSA (>2.5–4 ng/mL)
– Positive family history
• Benign nodule
– No significant change over time
– Nodule may be softer
– Prior episodes of prostatitis, biopsy, or prostate surgery (transurethral resection)
– Prior therapy with intravesical Bacillus Calmette–Guérin (BCG)
– Granulomatous nodules can be due to infectious causes (eg, tuberculosis [TB]) or systemic granulomatous diseases
Genetics
See “Prostate Cancer, General Considerations”
PATHOPHYSIOLOGY
• Normal prostate has a soft, uniform consistency.
• Prostate enlarges with age.
• Microscopically, nodular prostatic hyperplasia consists of nodules of glands and intervening stroma. May occasionally form benign palpable nodules.
• Nodule can be subjectively graded by degree of firmness/hardness (grades 1–3)
• CaP has to have a volume of 0.2 mL or larger to be detected by DRE.
ASSOCIATED CONDITIONS
• Prostate adenocarcinoma
• Benign prostatic hyperplasia (BPH)
• History of intravesical BCG for bladder cancer
GENERAL PREVENTION
None
DIAGNOSIS
HISTORY
• History of lower urinary tract symptoms
– Irritative voiding symptoms
– Obstructive voiding symptoms
– Fever
– Previous prostate biopsy or surgery such as TURP
– Previous pelvic external beam radiation or prostate brachytherapy
– History of prostatitis, abscess, or exposure to TB
– Systemic granulomatous disease (Wegner’s, etc.)
– Family history of genitourinary malignancies
ALERT
Where prostate abscess or acute prostatitis is suspected, rectal exam may be contraindicated.
PHYSICAL EXAM
• DRE
– Carcinoma (prostatic or urothelial cell carcinoma)
Firm, indurated nodules within the prostate gland
Prostate cancer most often arises in the posterior peripheral region of the prostate
Advanced prostate cancer can make the entire gland firm and cause obliteration of the medial and lateral sulci
Advanced cancer can also extend into the seminal vesicles or toward the side wall laterally
• BPH
– Prostate gland can be variably enlarged (size does not correlate with extent of voiding symptoms)
– Rubbery consistency
• Infectious lesions
– Prostatitis
Warm, tender prostate
Can be fluctuant or feel “boggy”
– Prostate abscess
Localized, fluctuant tender region in prostate
• Calculus can present as hard, small nodule
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• PSA
– Serum levels vary with age, race, and prostate volume
– Improves the positive predictive value of DRE for cancer
– No cut-off value below which the absence of prostate cancer can be guaranteed
Risk of prostate cancer is continuous as PSA increases (3)
– See “PSA Elevation, General Considerations” for further specifics on PSA
• Urinalysis
– Variable findings in men with abnormal DRE; sterile pyuria in granulomatous prostatitis
– Generally normal in men with prostate cancer without urinary tract infection
– Urine culture can be positive for gram-negative bacteria in acute and chronic bacterial prostatitis
– Urine cytology can be positive in urothelial cancer
Imaging
• Transrectal ultrasound (TRUS)
– Classic appearance of prostate adenocarcinoma is a round or oval hypoechoic lesion located in the peripheral zone
Not very sensitive as 39% of tumors can be isoechoic
Also nonspecific as granulomatous lesions can be hypoechoic
– BPH can have variable appearance
Distinguishable from prostate cancer only by biopsy
• Abdominal computed tomography (CT) or magnetic resonance imaging (MRI)
– Primarily used for staging purposes in patients with high-risk prostate cancer
• Bone scan to detect bone metastases
– Also primarily used for staging purposes in patients with high-risk prostate cancer
Diagnostic Procedures/Surgery
• TRUS-guided biopsy (4)
– Used to widely sample the prostate during biopsy in men with an elevated PSA and/or abnormal DRE
– Modern biopsy schemes have modified the standard sextant biopsy scheme to focus on laterally directed cores
Generally 12 cores
• Cystoscopy
– Used to evaluate bladder outlet obstruction and hematuria when present
Pathologic Findings
See “Prostate Cancer, General Considerations”
DIFFERENTIAL DIAGNOSIS
• Neoplasm, malignant
– Lymphoma, primary and secondary
– Prostate adenocarcinoma
– Other prostate malignancies
Sarcoma
Small cell carcinoma
Other more rare tumors and metastasis
– Urothelial carcinoma
• Benign
– BPH
– Calculus
– Ejaculatory duct cyst
– Granulomatous prostatitis
BCG related or other cause
– Scarring from prior radiation, surgery, or infection (TURP, etc.)
– Rectal wall lesions (thrombosed hemorrhoid, carcinoma, etc.)
TREATMENT
GENERAL MEASURES
• Abnormal DRE is an indication for TRUS-guided biopsy of the prostate
– Workup includes assessment of PSA
– Staging investigations including bone scan, CT, and/or MRI are reserved for high-risk cases as dictated by PSA, Gleason score, and DRE
MEDICATION
First Line
Antibiotics may be required for infectious causes of nodules such as bacterial prostatitis or TB
Second Line
N/A
SURGERY/OTHER PROCEDURES
See “Diagnostic Procedures/Surgery" above
ADDITIONAL TREATMENT
This is dictated by the results of the TRUS biopsy and presence/extent of prostate cancer
Radiation Therapy
While not a specific treatment of the nodule, it can be used as primary therapy or as additional adjuvant/salvage therapy after prostatectomy in patients with prostate cancer
Additional Therapies
May be required in cases with metastatic disease or disease that recurs after definitive local therapy
Complementary & Alternative Therapies
N/A
ONGOING CARE
PROGNOSIS
Depends on diagnosis after TRUS-guided biopsy
COMPLICATIONS
• TRUS-guided biopsy
– Hematuria
– Hematochezia
– Hematospermia
– Urinary tract infection or sepsis
– Urinary retention
Other complications are dictated by the treatment received for prostate cancer
FOLLOW-UP
Patient Monitoring
Negative biopsy in a patient with an abnormal DRE or elevated PSA requires follow-up with serial PSA and DRE
Patient Resources
• NCCN. http://www.nccn.org/patients/patientguidelines/prostate/
• American Cancer Society. http://www.cancer.org/cancer/prostatecancer/index?sitearea=%26dt=10
REFERENCES
1. Cooperberg MR, Lubeck DP, Mehta SS, et al. Time trends in clinical risk stratification for prostate cancer: Implications for outcomes (data from CaPSURE). J Urol. 2003;170:S21–S25; discussion S26–S27.
2. Shao YH, Demissie K, Shih W, et al. Contemporary risk profile of prostate cancer in the United States. J Natl Cancer Inst. 2009;101:1280–1283.
3. Thompson IM, Bermejo C, Hernandez J, et al. Screening for prostate cancer: Opportunities and challenges. Surg Oncol Clin N Am. 2005;14(4):747–760.
4. Trabulsi EJ, Halpern EJ, Gomella L. Ultrasonography and biopsy of the prostate. In: Wein AJ, Kavoussi LR, Novick AC, et al., eds. Campbell-Walsh Urology. 10th ed. Philadelphia, PA: Saunders; 2012:2735–2747.
ADDITIONAL READING
American Urological Association. Prostate-specific antigen (PSA): Best practice statement. http://www.auanet.org/education/guidelines/prostate-cancer-detection.cfm
See Also (Topic, Algorithm, Media)
• BCG Sepsis/BCG Ossis
• Prostate Biopsy, Infections and Complications
• Prostate Cancer, General Considerations
• Prostate Cancer, Localized (T1, T2)
• Prostate Cancer, Urothelial
• Prostate Nodule, Image 
• Prostatitis, Granulomatous
• Tuberculosis, Genitourinary, General Considerations
CODES
ICD9
• 600.10 Nodular prostate without urinary obstruction
• 600.11 Nodular prostate with urinary obstruction
• 790.93 Elevated prostate specific antigen [PSA]
ICD10
• N40.2 Nodular prostate without lower urinary tract symptoms
• N40.3 Nodular prostate with lower urinary tract symptoms
• R97.2 Elevated prostate specific antigen [PSA]
CLINICAL/SURGICAL PEARLS
• A firm prostate nodule generally deserves further workup with a serum PSA and prostate biopsy.
• Up to 40% of patients may develop granulomatous prostatitis after intravesical BCG that may present as a prostate nodule.