1. Memorial Sloan-Kettering Cancer Center
Significance of and Techniques to Reduce the Frequency of Positive Surgical Margins
James A. Eastham, MD
Memorial Sloan-Kettering Cancer Center
353 East 68th Street
New York, NY 10591
NOTE: The following slides are to be used for medical education purposes only. Copyright belongs to Prous Science and Prous Science is not responsible for any modification or change made by the users to these slides.

2. Index Definition of a positive surgical margin
Significance of a positive surgical margin
Surgical techniques to reduce the frequency of a positive surgical margin
Key words: prostate, radical prostatectomy, surgical margin

3. Definition of a Positive Surgical Margin
At the time of specimen processing, the outer surface of the radical prostatectomy is inked to define the margins of resection

4. Definition of a Positive Surgical Margin
A positive surgical margin is defined as “tumor on ink”, meaning the pathologist sees cancer cells directly in contact with ink at histological examination
Cancer cells abut the ink: positive margin

5. Significance of a Positive Surgical Margin
Multiple series suggest that a positive surgical margin is an independent predictor of biochemical recurrence (BCR) after radical prostatectomy (RP)1-5
This risk remains even after controlling for other known risk factors for BCR after RP, including pre-treatment PSA, RP Gleason score, presence or absence of extraprostatic cancer, presence or absence of seminal vesicle invasion and presence or absence of lymph node invasion

6. Multivariable Analysis of Risk of 10-year Progression after Radical Prostatectomy1
HR (95%) CI
p-value
+SM
1.52 ( )
0.002
Gleason sum
1.82 ( )
<0.0005
ECE
2.24 ( )
SVI
2.54 ( )
LNI
2.32 ( )
n=1389 patients ( )
+SM: Overall: 12.9%; pT2: 6.8%; pT3: 23%

7. Significance of a Positive Surgical Margin1
Even after controlling for other known risk factors of BCR after RP, a patient with a positive surgical margin is 1.5 times more likely to experience cancer recurrence than a patient with a negative surgical margin
Of these clinical and pathological features, only the status of the surgical margins has the potential to be influenced by the surgeon

8. Significance of a Positive Surgical Margin
Are positive surgical margins inherent in the nature of the cancer, like extracapsular extension, or can margins be influenced by the surgeon/surgical technique?

9. Surgeon’s Influence on the Likelihood of a Positive Surgical Margin2
Equal access medical center
Academic and private practice urologists
4629 RP performed by 44 individual surgeons
Question: What are the predictors of a positive surgical margin at the time of RP?
Analysis included known clinical and histological variables as well as surgical experience (number of RP performed) and individual surgeon

10. Multivariable Analysis for Risk of a +SM Based on Clinical and Pathological Parameters2
p-value
Serum PSA level
< 0.01
Extracapsular extension
Seminal vesicle invasion
0.86
Lymph node involvement
0.56
Radical prostatectomy Gleason sum
Surgical volume
0.01
Surgery date
Surgeon
0.05

11. Individual Surgeon and +SM Study2
The rate of +SM in RP specimens varies widely within and among hospitals and surgeons, whether at an open staffing hospital or a cancer referral center, and cannot be explained by surgical volume alone
Wide variations in +SM rates persist even when corrected for all known cancer prognostic factors
Differences in surgical technique, while hard to define, seem to result in substantial differences in positive margin rates and long-term cancer control rates

12. What Can Be Done to Decrease the Risk of a Positive Surgical Margin
Exposure and hemostasis
Appropriate extent of neurovascular bundle (NVB) preservation
Wide dissection including Denonvilliers’ fascia, lateral pedicle and bladder neck

13. What Can Be Done to Decrease the Risk of a Positive Surgical Margin at Open RP?
Exposure and hemostasis
8-10 cm lower midline incision
Slight flexion of table
Adequate retraction to expose the deep pelvis
Author’s choice: Turner-Warwick retractor
Appropriate extent of NVB preservation
Wide dissection including Denonvilliers’ fascia, lateral pedicle and bladder neck

14. The patient is positioned supine with the pubis just below the break point in the table. The table is flexed (~150o) and Trendelenburg rotation is applied to level the abdomen. An 8-cm suprapubic midline incision is made 3 fingers breadth above the penis.

15. What Can Be Done to Decrease the Risk of a Positive Surgical Margin?
Exposure and hemostasis
Prior to division of the dorsal venous complex (DVC): suture-ligate the DVC at bladder neck, mid-prostate and pelvic floor
Isolate DVC from urethra
Author’s choice: right-angled clamp and stainless steel wire
Divide DVC with knife and oversew cut-edge
Appropriate extent of NVB preservation
Wide dissection including Denonvilliers’ fascia, lateral pedicle and bladder neck

16. DVC ligated at bladder neck and
mid-prostate

17. Division of the DVC over a guide wire.
The DVC has been ligated proximally and distally. A right-angled clamp is passed beneath the DVC and grasps a wire. The DVC must be transected distal to all prostatic tissue.
The right angle clamp is used to pass a 22 g guide wire beneath the DVC. The wire serves as a template for precise guillotine transection of the DVC. The DVC is first ligated distally with a figure-of-8 suture before it is divided. By adjusting downward traction on the prostate with a sponge stick and upward traction on the guidewire, the point of transection of the DVC can be adjusted to avoid incision into the prostate. While positive surgical margins are not common in this area, it is difficult to anticipate when cancer is located anteriorly.

18. The cut edges of the DVC are
oversewn; the last bite being
taken through the periosteum
of the pubis

19. What Can Be Done to Decrease the Risk of a Positive Surgical Margin?
Exposure and hemostasis
Appropriate extent of NVB preservation
Thorough assessment of risk of cancer in the area of the NVB
Selection of appropriate plane of dissection
Intra-, Inter- or Extrafascial dissection
Wide dissection including Denonvilliers’ fascia, lateral pedicle and bladder neck

21. Endorectal MRI of prostate demonstrating the NVB and
possible planes of dissection7, 10

22. Feet
The extent of NVB
preservation is a balance between attempts to optimize the recovery of potency while at the same time removing all the cancer (a negative surgical margin). The majority of screen-detected prostate cancers will be candidates for complete NVB preservation (intrafascial dissection).
(R) Cavernous nerve
Prostate
Head

23. Apical Dissection with Nerve Sparing
1) Incision of lateral pelvic fascia above the nerve 2) Dissection of the NVB from apical third of the prostate 3) Sharp division of post layer of prostatorectal (Denonvilliers’) fascia
The NVB should be dissected distally away from the apex and the proximal urethra. The posterior layer of Denonvilliers (prostatorectal) fascia also covers the NVB medially. This fascia must be divided, exposing the layer of adipose tissue anterior to the rectum, the correct plane of dissection. The posterior layer of the prostatorectal fascia should be left on the prostate to minimize the risk of a posterior positive margin.

24. Click on the link below to start the video. The initial mobilization of
the NVB is complete. The scissors sharply incise Denonvilliers’
fascia exposing the yellow fat of the anterior rectal wall

25. Wide resection of the right NVB in the area of a large, palpable cancer. The dissection is facilitated by starting the dissection laterally such that all periprostatic tissue can be resected
When cancer lies over the NVB, some or all of the bundle should be resected to assure a negative margin.

26. Transection of the Bladder Neck Wide dissection of the lateral pedicles around the base, and transection of the bladder neck above the prostate, will reduce the risks of positive margins. “Bladder neck preservation” does not improve continence.
There should be ample tissue in the angle between the base of the prostate and the seminal vesicles.
The bladder neck is transected proximal to the prostatic urethra to reduce the risk of a positive bladder neck margin. Preservation of the bladder neck does not improve long term continence. The specimen should contain abundant tissue in the angle between the base of the prostate and the seminal vesicles.
Leave more tissue here

27. Conclusions
Positive surgical margins are an adverse prognostic feature at the time of RP
Of all prognostic factors, this is the only one modifiable by surgical technique
Most patients can undergo preservation of the majority of the tissue at the NVB and still have complete resection of their cancer (negative surgical margin)
Patient selection, complete resection of Denonvilliers’ fascia and wide resection at the bladder neck have been shown to reduce the incidence of a positive surgical margin

28. References
Swindle, P., Eastham, J.A., Ohori, M., Kattan, M.W., Wheeler, T., Maru, N., Slawin, K., Scardino, P.T. Do margins matter? The prognostic significance of positive surgical margins in radical prostatectomy specimens. J Urol 2005, 174:
Eastham, J.A., Kattan, M.W., Riedel, E., Begg, C.B., Wheeler, T.M., Gerigk, C., Gonen, M., Reuter, V., Scardino, P.T. Variations among individual surgeons in the rate of positive surgical margins in radical prostatectomy specimens. J Urol 2003, 170:
Karakiewicz, P., Eastham, J., Graefen, M., Cagiannos, I., Stricker, P., Klein, E., Cangiano, T., Schröder, F., Scardino, P., Kattan, M. Prognostic impact of positive surgical margins in surgically treated prostate cancer: Multi-institutional assessment of 5831 patients. Urology 2005,  66:
Ward, J.F., Zincke, H., Bergstralh, E.J., Slezak, J.M., Myers, R.P,, Blute, M.L. The impact of surgical approach (nerve bundle preservation versus wide local excision) on surgical margins and biochemical recurrence following radical prostatectomy. J Urol 2004, 172:

29. References
Palisaar, R-J., Noldus, J., Graefen, M., Erbersdobler, A., Haese, A., Huland, H. Influence of nerve-sparing (NS) procedure during radical prostatectomy (RP) on margin status and biochemical recurrence. Eur Urol 2004, 47:
Eastham, J.A., Scardino, P.T. Radical prostatectomy for clinical stage T1 and T2 prostate cancer. In: Comprehensive Textbook of Genitourinary Oncology 2002, (Ed. Vogelzang, N) Philadelphia: Lippincott Williams & Wilkins.
Montorsi, F., Salonia, A., Suardi, N. Improving the preservation of the urethral sphincter and neurovascular bundles during open radical retropubic prostatectomy. Eur Urol 2005, 48: 938–945.
Walsh, P.C., Partin, A.W., Epstein, J.I. Cancer control and quality of life following anatomical radical retropubic prostatectomy: results at 10 years. J Urol 1994, 152:

30. References
9. Naya, Y., Slaton, J.W., Troncoso, P., Okihara, K., Babaian, R.J. Tumor length and location of cancer on biopsy predict side specific extraprostatic cancer extension. J Urol 2004, 171:
10. Graefen, M., Walz, J., Huland, H. Open retropubic nerve-sparing radical prostatectomy. Eur Urol 2006, 49: 38–48.