Kiranpreet K. Khurana, MD
Eric A. Klein, MD, FACS
BASICS
DESCRIPTION
• Prostate cancer that extends to the margin of resection upon pathologic analysis of radical prostatectomy specimen
• May be reported as: Focal or extensive, solitary or multiple
EPIDEMIOLOGY
Incidence
• 5–27% for organ-confined prostate cancer (1)
• 17–65% for nonorgan-confined prostate cancer (1)
Prevalence
N/A
RISK FACTORS
• Higher preoperative prostate-specific antigen (PSA)
• Higher clinical stage
• Higher Gleason score
• Higher pathologic stage
• Surgeon experience
Genetics
None directly correlate with positive surgical margin (PSM)
PATHOPHYSIOLOGY
• 3 causes of PSM:
– Tumor extends beyond prostate to margin of resection
– Disruption of prostate capsule exposed cancerous glands
– Artifact from intraoperative manipulation of prostate or pathologic processing
ASSOCIATED CONDITIONS
Nonorgan-confined prostate cancer: Higher likelihood of PSM compared to organ confined
GENERAL PREVENTION
• Do not dissect too closely at prostatic apex or posterolaterally since PSM frequently seen there
• For radical prostatectomy, choose surgical approach with most familiarity to surgeon
DIAGNOSIS
HISTORY
History of risk factors (higher PSA, clinical stage, and Gleason grade) may increase chance of PSM
PHYSICAL EXAM
Digital rectal exam has been shown to be unnecessary if PSA is undetectable
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Monitor PSA at follow-up visits
• In patients with PSM, there is 25–40% chance of subsequent biochemical recurrence (1)[B]
Imaging
• No additional imaging needed after radical prostatectomy for PSM unless there is suspicion of locoregional recurrence or metastatic disease
• Bone scan, pelvic MRI, and/or computer tomography scan may be considered if above suspected (2)[C]
• Indium In 111 ProstaScint is also indicated as a diagnostic imaging agent in postprostatectomy patients with a rising PSA and a negative or equivocal standard metastatic evaluation in whom there is a high clinical suspicion of occult metastatic disease. Limited utility for use in this setting
Diagnostic Procedures/Surgery
None indicated
Pathologic Findings
• PSM is a pathologic diagnosis
– Most common site is prostatic apex
– Posterolateral margin and bladder neck also commonly involved
– Note that capsule is missing at the apex, so PSM at the apex may be artifactual
• Often classified as: Focal or extensive, solitary or multiple
– Extensive and/or multiple PSM increase chance of biochemical recurrence, but these subclassifications of PSM do not have greater predictive usefulness than comparing positive vs. negative surgical margin alone (1)[B]
DIFFERENTIAL DIAGNOSIS
• Nonorgan-confined disease with extraprostatic extension or locally advanced disease
• Iatrogenic capsular incision
TREATMENT
GENERAL MEASURES
• Surgical approach (open, laparoscopic, robotic) does not appear to influence rate of PSM (3)[B]
– Use good surgical principles to avoid PSM
– PSM vary by different pathologic sectioning
– Surgical experience decreases rate of PSM
MEDICATION
First Line
N/A
Second Line
N/A
SURGERY/OTHER PROCEDURES
N/A
ADDITIONAL TREATMENT
Radiation Therapy
• External beam, delivered as 3D-conformal or intensity modulated
– 64–65 Gy usual dose
• Adjuvant radiotherapy shown to decrease biochemical and local recurrence, and clinical progression (2)[A]
• Effect on subsequent metastasis and overall survival not as clear
• Treatment with adjuvant radiotherapy results in lower use of salvage treatment
• Since majority of patients with PSM do not develop clinical recurrence, immediate adjuvant radiotherapy may lead to overtreatment
• However, salvage radiotherapy may not be as effective for high-risk disease
• Controversy over use of immediate vs. salvage adjuvant therapy
Additional Therapies
• ·Radiation Therapy Oncology Group trial 9601 is investigating radiotherapy with or without long-term androgen deprivation in postprostatectomy men with pT3N0 disease or pT2N0 disease with a positive margin with PSA ≥0.2–4 ng/mL
– Preliminary results show that 24 mo of antiandrogen therapy (bicalutamide) and radiotherapy improve biochemical-free survival and incidence of metastatic disease
– Full results awaited
• Radiotherapy and androgen deprivation in combination after local surgery (RADICALS) trial is evaluating immediate adjuvant radiotherapy vs. salvage radiotherapy
– Also addresses role of androgen deprivation
– Results awaited
Complementary & Alternative Therapies
See “Additional Therapies” above
ONGOING CARE
PROGNOSIS
• Not all PSM result in biochemical recurrence, nor higher risk of metastatic disease and death, but those with PSM are at higher risk of both than those with negative margins; these risks are associated with other pathologic features as well
• Prediction tools such as http://nomograms.mskcc.org/Prostate/PostRadicalProstatectomy.aspx are used at some centers for decision making concerning postradical prostatectomy management
• Preliminary results with new genomic classifers may indicate which patients might benefit form adjuvant radiaion therap (4)
COMPLICATIONS
• Complications related to radiotherapy (2):
– Grade 1 or 2 acute toxicities: Common, up to 45%
– Grade 3 or 4 acute toxicities: Up to 20%
– Up to 28% may develop late toxicities
Urinary incontinence, stricture more common than gastrointestinal toxicities (proctitis)
FOLLOW-UP
Patient Monitoring
• PSA every 3–6 mo for 1st 3–5 yr, then annually thereafter
– Value ≥0.2 ng/dL after surgery with confirmatory value of ≥0.2 ng/dL defines biochemical recurrence
Patient Resources
American Cancer Society. http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-treating-recurrence
REFERENCES
1. Stephenson AJ, Wood DP, Kattan MW, et al. Location, extent, and number of positive surgical margins do not improve accuracy of predicting prostate cancer recurrence after radical prostatectomy. Journal of Urology. 2009;182:1357–1363.
2. Thompson IM, Valicenti R, Albertsen PC, et al. Adjuvant and salvage radiotherapy after prostatectomy: ASTRO/AUA Guideline. 2013. Available online at https://www.auanet.org/common/pdf/education/clinical-guidance/Radiation-After-Prostatectomy.pdf.
3. Eastham JA, Kattan MW, Riedel E, et al. Variations among individual surgeons in the rate of positive surgical margins in radical prostatectomy specimens. J Urol. 2003;170:2292–2295.
4. Den RB, Feng FY, Showalter TN, et al. Genomic prostate cancer classifier predicts biochemical failure and metastases in patients after postoperative radiation therapy. Int J Radiat Oncol Biol Phys.2014;89(5):1038–1046.
ADDITIONAL READING
Touijer K, Kuroiwa K, Eastham JA, et al. Risk-adjusted analysis of positive surgical margins following laparoscopic and retropubic radical prostatectomy. Eur Urol. 2007;52:1090–1096.
See Also (Topic, Algorithm, Media)
• Prostate Cancer, Biochemical Recurrence (Elevated PSA) Following Radical Prostatectomy
• Prostate Cancer, Locally Advanced (Pathologic T3, T4)
• Prostate Cancer, Positive Margin Following Radical Prostatectomy Image 
• PSA Elevation, General
• Reference Tables: TNM: Prostate Cancer
CODES
ICD9
• 185 Malignant neoplasm of prostate
• V45.77 Acquired absence of organ, genital organs
ICD10
• C61 Malignant neoplasm of prostate
• Z90.79 Acquired absence of other genital organ(s)
CLINICAL/SURGICAL PEARLS
• PSM most commonly found at prostatic apex, posterolaterally, and bladder neck.
• Avoid overzealous dissection at these locations during radical prostatectomy in patients suspected of being high-risk for PSM.
• PSM are diagnosed pathologically and may be real or artifactual.
• Subset of men with PSM develop biochemical recurrence.
• Adjuvant radiotherapy decreases chance of biochemical and local recurrence but effect on metastatic disease and overall survival not clear.