Originally published 7/20/2015
As a treatment for prostate cancer (PCa), prostatectomy (surgical gland removal) continues to be dogged by positive surgical margins (PSMs). Patients who have PSMs are at higher risk for recurrence. The issue is not the surgical approach (open, laparoscopic, or robot-assisted laparoscopic), since the rates of positive margins are comparable across all methods. The problem is, can we predict PSM before surgery and, if so, how will it affect the treatment plan? There is a body of research on clinical factors such as PSA, Gleason grade and tumor stage used to estimate the probability of PSMs. However, pre-surgical imaging with multiparametric MRI (mpMRI) is a gamechanger. It helps eliminate the guesswork by providing a high-resolution portrait of the tumor itself.
mpMRI A Korean team of radiologists created a simple scoring system with good PSM prediction performance for all PCa risk levels.[i] They identified the three factors that act as independent predictors: a) tumors that manifest contact to the prostate apex or posterolateral aspect (the part of the gland that can be felt during a digital rectal exam); b) the length of tumor contact with the capsule, or outer surface of the gland; and c) higher PI-RADS category. These three factors cannot be determined without imaging, but higher scores in this system correlate significantly with PCa risk level calculated on conventional clinical factors. This is a tremendous aid in planning treatment so as to minimize the potential for recurrence (e.g., nerve-sparing surgery may not be recommended; adjuvant radiation may be included; etc.) Thus, mpMRI has brought us much closer to the day when there are no unpleasant surprises after surgery, as described in the original blog below.
The Harvard Medical School is a recognized and authoritative source of correct information about prostate cancer (PCa). Their website has information about anxiety-provoking news after radical prostatectomy, or RP: positive surgical margins (PSMs). No matter how meticulous a surgeon’s technique, there will always be cases in which a tumor has extended beyond where the scalpel cannot cut it all out. Harvard’s site describes the impact of this news on the patients who must hear it:
[With] the radical prostatectomy complete, they head home from the hospital believing they have been cured, only to learn that some cancer may have been left behind. Today, about 10% to 20% of patients …receive this news.[ii]
In fact, the number of these disappointed men may be even higher. In a new French study, “Positive Surgical Margins After Radical Prostatectomy: What Should We Care About?” the authors state that PSMs are a “known factor associated with biochemical recurrence” (rising PSA after treatment).[iii] They studied 630 RP cases from 2005-08, and report that 206 of them (32.7% or almost a third) had PSMs.
As I said, this is worrisome news but it’s not necessarily catastrophic. A patient with PSMs will be reassured that this doesn’t inevitably mean that in the future his cancer will begin to grow. He will be carefully monitored. If his PSA begins to rise, it will likely trigger a biopsy; if positive for PCa, he may be a candidate for a salvage treatment such as radiation or ablation—both of which are potentially curative. If his pre-RP risk factors (Gleason score, stage, PSA) indicate a higher level of tumor aggression, he may immediately be offered what is called post-surgical adjuvant radiation. This means having a course of radiation to the pelvic bed beginning around 6 weeks after his surgery, with the intent of killing any cancer cells there before they can spread further. While there is a risk of side effects that affect his healing after surgery, adjuvant radiation can save lives.
The French team chose 110 of the PSM patients who had no surgical evidence of lymph node involvement, whose post-surgical PSA was undetectable, and who did not receive adjuvant radiation therapy. The team analyzed their pre-surgery risk factors and their surgical pathology reports, and followed them for an average of 6 years. The biochemical recurrence rate (BCR) was 30%. “The factors significantly associated with BCR were preoperative PSA, predominance and percentage of Gleason 4, tumor volume, PSA length and predominance of Gleason 4 at the margin.
One thing that struck me about this study was a concluding sentence that reads, “Over a 5-year follow-up, only one-third of patients experienced BCR.” I found myself thinking, ONLY one-third? I did some quick mental math by imagining a huge auditorium where 1,000 prostate cancer patients who are scheduled for prostatectomy are attending a pre-op class. After their operations, 327 of them (32.7%) learn that they had PSMs. Within 72 months, just over 100 men (roughly a third of the 327) now have biochemical recurrence, and many will go on hormones since they can’t have a salvage therapy. It will be no consolation for any of them to know that he was part of “only one-third” of his fellow patients.
The other thing that got my attention was the title question: What Should We Care About? My answer is, we should care about better diagnosis before a man is sent for surgery. We should care about knowing in advance if his tumor has penetrated the prostate capsule, and 3T multiparametric MRI can show us that. We should care about the cell line, because with new tests like the 4K score and other genomic analysis, we can have advance knowledge about how dangerous those cells actually are. We should care about NOT putting a man through surgery if he is either a) a candidate for focal therapy or b) his disease has already begun to spread where a scalpel can’t get it so he needs to consider other options such as radiation.
Reading this article had a big impact on me. My heart goes out to PCa patients who have gone through surgery only to learn they may still have a time bomb ticking in their bodies. The article makes me more determined than ever to raise awareness about the value of multiparametric MRI and the latest ways to assess the true nature of an individual’s prostate cancer. I hope the day comes soon when no man has to hear that after all he went through from diagnosis to decision to treatment—he has positive surgical margins.
NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.
[i] Park MY, Park KJ, Kim MH, Kim JK. Preoperative MRI-based estimation of risk for positive resection margin after radical prostatectomy in patients with prostate cancer: development and validation of a simple scoring system. Eur Radiol. 2021 Jul;31(7):4898-4907.
[iii] Pettenati C, Neuzillet Y, Radulescu C et al. Positive surgical margins after radical prostatectomy: What should we care about? World J Urol. 2015 May 5. [Epub ahead of print] http://www.ncbi.nlm.nih.gov/pubmed/?term=pettenati+Neuzillet+positive+surgical+margins