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Multifocality and Multilocation of Positive Margins Predict Biochemical Recurrence of Prostate Cancer

Key findings

  • A positive surgical margin (PSM) is well known to predict biochemical-free recurrence (BCR) of prostate cancer, but the effects of multifocality and multilocation of PSMs are less well understood
  • In this retrospective study, multilocation PSM was an independent prognostic factor for BCR
  • The combination of multifocal and multilocation PSM was associated with particularly poor prognosis
  • Patients with a single-location, single-focal PSM at the apex were unlikely to develop BCR

A positive surgical margin (PSM) after radical prostatectomy for localized prostate cancer is a strong predictor of biochemical recurrence (BCR). Adjuvant radiation therapy can reduce the risk of BCR, but it is not well understood which patients with PSM need it, so radiation might be overused.

Studies of PSM have mainly focused on its location, number and length, with PSM at the apex being most common and associated with the best BCR-free survival. The effect of PSM multifocality on prognosis has varied in different studies, and few studies have examined the prognostic role of multilocation PSM.

Using a prostate cancer database, Chin-Lee Wu, MD, PhD, director of Genitourinary Pathology Services at Massachusetts General Hospital, and colleagues recently determined that multifocality and multilocation of PSMs, and especially their combination, provide additional prognostic information for patients with prostate cancer. They report their findings in Clinical Genitourinary Cancer.

The researchers reviewed 3,357 patients who underwent radical prostatectomy for localized prostate cancer between 1993 and 2007. They excluded those who had neoadjuvant therapy, adjuvant therapy directly after surgery, positive lymph nodes or postoperative elevated prostate-specific antigen, and those who were lost to PSA follow-up.

Of the 2,796 remaining patients, 476 had PSMs and became the sample for the study. The patients were classified according to PSM status:

  • sLsF: Single location containing single-focal PSM (70.4%)
  • sLmF: Single location containing multifocal PSM (14.9%)
  • mLsF: Multilocation containing separate single-focal PSM (9.2%)
  • mLmF: Multilocation(s) containing multifocal PSM (5.5%)

The median follow-up of the patients was 12.9 years. Patients with single-location, single-focal PSMs had significantly better BCR-free survival when compared with the three other groups together.

The researchers then compared all patients with single-location PSMs against all patients with multilocation PSMs. They found significantly better BCR-free survival for patients with single-location PSMs.

Next, the research group studied BCR-free survival for each of the four PSM groups individually. The sLsF group had the best prognosis, followed by the sLmF group. The prognosis for the mLsF group was significantly worse than that of the sLsF group.

The mLmF group had the worst prognosis of all in terms of BCR-free survival, but the combination of multilocation and multifocality was not associated with poorer metastasis-free survival or overall survival.

Clinicians could analyze the combination of PSM focality and location status as a surrogate for the length of PSM, the researchers suggest.

They believe multilocation PSM probably indicates a large volume of residual cancer cells occupying different pathologic locations in the surgical bed such that patients develop a more aggressive disease.

Finally, the research group divided the sLsF group into patients who had PSM found at the apex location and those whose PSM was peripheral or at the bladder neck. The apex sLsF group had significantly better BCR-free survival compared with the non-apex sLsF group, as well as compared with the three other PSM groups.

This novel finding suggests that adjuvant therapy is not necessary for patients with sLsF PSMs at the apex.


Active surveillance (AS) has become an accepted way to manage prostate cancer in men at lower risk. Multiparametric MRI can be used in conjunction with the standard transrectal ultrasound (TRUS)-guided biopsy to improve detection of clinically significant cancers.


Current treatments generally focus on oral medications or invasive surgery, which can have side effects. The prostatic urethral lift and water steam therapy are effective, non-invasive treatments for BPH.