This presentation is prepared for a medical debate for one of my clients, as such I couldn't disclose his name. However, I thought it might be useful to other medicos who might be looking for it or relevant to it, the same way slideshare helped me find some useful presentations earlier. - Vijay

1. Radical Prostatectomy (RP)
in Patients with High Serum
PSA values - A Surgical
Expertise
Views Against..
Vijay Elipay
Asst Manager, Med Info Services

2. Radical Prostatectomy (RP)
● Surgery is a common choice if prostate
cancer does not spread outside the
prostate, the main type being radical
prostatectomy
● Radical prostatectomy (RP) is the
removal of the entire prostate gland plus
some of the tissue around it, including the
seminal vesicles.

3. Radical Prostatectomy
● 1/3rd of patients undergo RP as initial
therapy
● 25-33% of patients are at risk of
treatment failure following RP
● 60-70% will develop metastatic disease
within 10 years without further treatment

4. RP can be done in different ways
● Open approaches
▪ Radical retropubic prostatectomy (RRP)
▪ Radical perineal prostatectomy
● Laparoscopic approaches
▪ Laparoscopic RP
▪ Robotic-assisted laparoscopic RP

5. Open approaches to RP

6. Radical Retropubic Prostatectomy
(RRP)
● Incision (cut) in lower abdomen, from the belly button down to
the pubic bone.
● Reasonable chance the cancer might have to nearby lymph nodes
(based on PSA level, prostate biopsy results), the surgeon may
also remove some of these lymph nodes at this time
● Stay in the hospital for a few days after the surgery, and
activities will be limited for several weeks.
● If cancer cells are found in any nodes, the surgeon might
not continue with the surgery. This is because it’s unlikely
that the cancer can be cured with surgery, and removing
the prostate could lead to serious side effects.
http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-treating-surgery

7. Radical Perineal Prostatectomy
● Incision in the skin between the anus and scrotum (the
perineum).
● Used less often because it’s more likely to lead to
erection problems and the nearby lymph nodes can’t
be removed.
● Often a shorter operation and might be an option if not
concerned about erections and don’t need lymph nodes
removal.
● Usually takes less time than the retropubic operation, and
may result in less pain and an easier recovery afterward.
● Stay in the hospital for a few days after the surgery, and
activities will be limited for several weeks.
http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-treating-surgery

8. Laparoscopic RP
● Several small incisions to remove the prostate. instrument
has a small video camera on the end, to see inside the
abdomen.
● Some advantages over open radical prostatectomy, less
blood loss and pain, shorter hospital stays, and faster
recovery times
● LRP appears to be as good as open radical prostatectomy,
although we do not yet have long-term results.
● Rates of major side effects such as erection problems
and incontinence seem to be about the same as for
open prostatectomy. Recovery of bladder control may
be delayed slightly
http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-treating-surgery

9. Robotic-assisted Laparoscopic RP or
Robotic Prostatectomy
● Robotic interface (da Vinci system).
● Advantages over the open approach in terms of
less pain, blood loss, and recovery time.
● Side effects most concerned about, such as
urinary or erection problems, there doesn’t
seem to be a difference between robotic
prostatectomy and other approaches.
● Most important factor in the success of either
type of laparoscopic surgery is the surgeon’s
experience and skill.
http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-treating-surgery

10. Side Effects of Prostate Surgery
● Major side effects are
▪ urinary incontinence
▪ erectile dysfunction
● Doctors can’t predict for sure how any man will be affected
after surgery. In general, older men tend to have more
incontinence problems.
● Ability to have an erection after surgery depends on age,
ability to get an erection before the operation, and whether
the nerves were cut.
● All men can expect some decrease to have an erection, but
the younger are more likely to keep this ability.
http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-treating-surgery

11. History of Prostate-specific Antigen (PSA)

12. Characteristics of men, number of patients
(percentage), undergoing RP at Johns
Hopkins Hospital
Characteristic 2006-2011 200-2005
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13. Stamey TA et al N Engl J Med. 1987 Oct 8;317(15):909-16.
Prostate-specific Antigen
as a Serum Marker for
Adenocarcinoma of the
Prostate

14. Prostate-specific antigen as a serum marker
for adenocarcinoma of the prostate
● To compare clinical usefulness of prostate-specific antigen
(PSA) and prostatic acid phosphatase (PAP)
● 2,200 serum samples from 699 patients, 378 of whom had
prostatic cancer.
● PSA elevated in 122 of 127 patients with newly diagnosed,
untreated cancer, including 7 of 12 patients with
unsuspected early disease and all of 115 with more
advanced disease.
● PSA↑ in 86% and PAP↑ in 14% of the patients with BPH.
Stamey TA et al N Engl J Med. 1987 Oct 8;317(15):909-16

15. Prostate-specific antigen as a serum marker
for adenocarcinoma of the prostate
Stamey TA et al N Engl J Med. 1987 Oct 8;317(15):909-16
Preoperative serum concentration of PSA in relation to
cancer volume in 45 patients undergoing consecutive RP
(log-log plot)

16. Prostate-specific antigen as a serum marker
for adenocarcinoma of the prostate
Stamey TA et al N Engl J Med. 1987 Oct 8;317(15):909-16
PSA, TAP and PAP after radical prostatectomy

17. Prostate-specific antigen as a serum marker
for adenocarcinoma of the prostate – cont..
● After radical prostatectomy, PSA routinely fell to undetectable
levels, with a half-life of 2.2 days. If initially elevated, PAP fell to
normal levels within 24 hours but always remained detectable.
● In 6 patients followed postoperatively by means of repeated
measurements, PSA--but not PAP--appeared to be useful in detecting
residual and early recurrence of tumor
● Prostate massage increased the levels of both PSA and PAP
approximately 1.5 to 2 times. Needle biopsy and transurethral
resection increased both considerably.
● Therefore, PSA is more sensitive than PAP in the detection of
prostatic cancer and will probably be more useful in
monitoring responses and recurrence after therapy. However,
since PSA may be elevated in benign prostatic hyperplasia, it
is not specific.
Stamey TA et al N Engl J Med. 1987 Oct 8;317(15):909-16

18. Frazier HA et al J Urol. 1993 Mar; 149(3):516-8.
Is Prostate-specific
Antigen of Clinical
Importance in Evaluating
Outcome after Radical
Prostatectomy?

19. Is prostate specific antigen of clinical importance in
evaluating outcome after RP?
● Background: ↑serum PSA after RP infers failure of
procedure.
● Since April 1987 preoperative and postoperative serum PSA
levels from 226 patients who had radical perineal
prostatectomy for presumed organ confined prostate cancer
(stage T1-2N0M0).
● Clinical failure as defined by elevation of serum acid
phosphatase, biopsy proved local recurrence or evidence of
malignant disease on bone scan occurred in 3.9% of patients
with organ confined, 7.0% with specimen confined and 13.2%
with margin positive disease.
▪ When PSA elevation of >0.5 ng./ml was used, failure rate became
9.8% for organ confined group, 39.4% for specimen
confined group and 66.0% for margin positive group.
Frazier HA et al J Urol. 1993 Mar; 149(3):516-8

20. Is prostate specific antigen of clinical importance in
evaluating outcome after radical prostatectomy?
● Of patients who failed clinically interval from initial elevation
of postoperative PSA to clinical detection of failure ranged
from 2 to 28 months (median 16).
● Among patients with an elevated postoperative PSA level but
who have not failed clinically follow-up ranged from 4 to 46
months (median 23).
● 11 patients had no evidence of failure at >36 months despite
elevated postoperative serum PSA level.
● These PSA elevations in patients who undergo supposed
curative therapy are distressing. However, at this time
majority of these patients have not failed. In clinically cured
patient biochemical evidence of failure may not be
sufficient to change the treatment course
Frazier HA et al J Urol. 1993 Mar; 149(3):516-8

21. Ruckle HC et al Mayo Clin Proc. 1994
Jan;69(1):69-79
Prostate-specific Antigen:
Concepts for Staging
Prostate Cancer and
Monitoring Response to
Therapy.

22. Prostate-specific antigen: concepts for staging prostate
cancer and monitoring response to therapy
● PSA level alone does not facilitate precise pathologic staging
although advanced stage tends to correlate with increased
PSA level.
● Staging accuracy of PSA, can be enhanced by considering
the variables of tumor grade and clinical stage.
● Staging radionuclide bone scans in asymptomatic, untreated
patients with clinically localized prostate cancer and a PSA value
<10.0 ng/mL are unnecessary.
● After RP, serum PSA level is exquisitely sensitive to
recurrent or residual disease.
● Ultrasensitive PSA assays can ↑sensitivity of PSA as a tumor
marker after RP.
▪ However, clinical usefulness of PSA concentrations detected in the
ultrasensitive range after RP is unknown.
Ruckle HC et al Mayo Clin Proc. 1994 Jan;69(1):69-79

23. Pound CR et al.
Natural History of
Progression after PSA
Elevation following Radical
Prostatectomy
Pound CR et al, JAMA. 1999 May 5;281(17):1591-7.

24. Natural history of progression after PSA
elevation following radical prostatectomy
● CONTEXT: In elevated serum PSA after RP, natural history of
progression to distant metastases and death due to PCa is unknown.
● OBJECTIVE: To characterize time course of disease progression with
biochemical recurrence after RP
● DESIGN: Retrospective review of a large surgical series with median
(SD) follow-up of 5.3 (3.7) years (range, 0.5-15 years) between April
1982 and April 1997.
● PATIENTS: Total 1,997 men undergoing RP, by a single surgeon, for
clinically localized PCa. None received neoadjuvant therapy, or
adjuvant HT prior to documented distant metastases.
● MAIN OUTCOME MEASURES: After surgery, PSA assays and DREs
every 3 months for 1st year, semiannually for 2nd year, and annually
thereafter. A detectable serum PSA level of at least 0.2 ng/mL was
evidence of biochemical recurrence.
Pound CR et al, JAMA. 1999 May 5;281(17):1591-7.

25. Natural history of progression after PSA
elevation following radical prostatectomy
● RESULTS:
▪ Metastasis-free survival for all 1,997 men was 82% (76%-88%) at 15
years after surgery. 315 (15%) developed PSA level elevation.
103 (34%) developed metastatic disease within the study
period.
▪ Median time to metastases - 8 years from time of PSA level
elevation.
▪ In survival analysis, time to biochemical progression (P<.001),
Gleason score (P<.001), and PSA doubling time (P<.001) were
predictive of the probability and time to the development of metastatic
disease.
● CONCLUSIONS: Several clinical parameters help predict
the outcomes of men with PSA elevation after radical
prostatectomy.
Pound CR et al, JAMA. 1999 May 5;281(17):1591-7.

26. McIntosh HM et al British Journal of Cancer (2009) 100,
1852–1860
Follow-up Care for Men
with Prostate Cancer and
the Role of Primary Care: a
Systematic Review of
International Guidelines

27. Follow-up care for men with prostate cancer and the
role of primary care: a systematic review of
international guidelines
● Optimal role for primary care in providing follow-up for men
with Pca is uncertain.
● Systematic review of international guidelines to identify
existing models of f/u care for evaluating future complex
interventions.
● Many guidelines provide insufficient information to judge the
reliability of the recommendations. Although the PSA test
remains cornerstone of follow-up, diversity of
recommendations on provision of follow-up care reflects lack
of research evidence on which to base firm conclusions.
● Importance of transparent guideline development procedures
and need for robust primary research for evidence-based
models of f/u care for PCa
McIntosh HM et al British Journal of Cancer (2009) 100, 1852–1860

28. Follow-up care for men with prostate cancer and the role of
primary care: a systematic review of international guidelines
Guidelines follow-up recommendations on PSA testing
McIntosh HM et al British Journal of Cancer (2009) 100, 1852–1860
Guideline Quality* Prostatectomy
Finnish Current Care
Guidelines (FCCG)
High 6 – 12 months after surgery, then every 6 months for 5 years, then
every 12 months
Alberta Cancer Board (ACB) Low 4 – 8 weeks after surgery, then every 6 months for 2 years, then
annually
European Society for Medical
Oncology (ESMO)
Low PSA should be monitored
Standards, Options and
Recommendations (SOR)
Moderate Between 1 and 3 months, then every 3 months in the first year (less
if < limit of detection) and every 6 months for the next 7 years
Cancer Care Nova Scotia
(CCNS)
Moderate Every 3 –12 months in years 1 – 3 and every 6 – 12 months from
year 3 onwards
French Urological Association
(AFU)
Low Within 3 months, then at 6 months, then, every 6 months for 3
years, then annually
Ontario Ministry of Health and
Long-Term Care (OMHLTC)
Moderate At 3 – 12-month intervals
British Colombia Cancer
Agency (BCCA)
Low Every 3 months in the first year, then every 6 months
American Urological
Association (AUA)
Moderate Periodic

29. Follow-up care for men with prostate cancer and the
role of primary care: a systematic review of
international guidelines
McIntosh HM et al British Journal of Cancer (2009) 100, 1852–1860
● PSA testing:
▪ International guidelines agree on the fundamental
role of PSA testing in PCa follow-up
▪ But, recommendations on frequency of tests and
duration of follow-up are highly inconsistent
▪ Recommended interval between PSA tests in 1st year
following prostatectomy: 3 - 12 months
▪ Marked variation in recommended frequency of
routine testing relative to duration beyond 1st year
▪ High degree of variability between guidelines on
what defines biochemical failure, i.e., change in
PSA that should prompt further investigation

30. Radical Prostatectomy: Biochemical Relapse
Factors Associated with Metastatic Disease and Death
● Persistently elevated PSA after
Prostatectomy
● Shorter interval from surgery to
biochemical relapse
● Shorter PSA doubling time

31. Radical Prostatectomy
GPSM Scoring Algorithm
GPSM – Prostatectomy Gleason Score
+ 1 (Pre-op PSA 4-10)
+ 2 (Pre-op PSA 10.1-20)
+ 3 (Pre-op PSA >20)
+ 2 (+S.V. or +Nodes)
+ 2 (Positive Surgical Margins)
GPSM score of >10: Increased biochemical
relapse; Increased risk of death

32. GPSM Scoring Outcomes

33. Radical Prostatectomy:
Post-op PSA kinetics (doubling time)
● PSA Working Group Guidelines for PSAdt (PSA
doubling time) calculations
● >3 PSA values which are >0.2 ng/ml and
increasing within 12 months
● Stable testosterone levels (not recovering from
androgen suppression)
● Relationship of PSAdt clinical relapse and
mortality – continuum

34. Radical Prostatectomy:
PSA doubling time
● Strongly associated with clinical relapse
● PSAdt <3 months: Short life expectancy
● PSAdt <12 months: 50-75% of patients
with clinical relapse within 10 years
● PSAdt <15 months: 90% deaths due to
prostate cancer

35. Radical Prostatectomy:
Biochemical Relapse
● Abnormal CT is rare with:
◦ PSA < 5-10 ng/ml
◦ PSAdt > 6-10 months
● Abnormal bone scan is rare with:
◦ PSA < 10 ng/ml

36. What I’m trying to say..
● PSA is a sensitive biochemical marker in the detection of PCa
and will probably be more useful in monitoring responses and
recurrence after therapy. However, since PSA may be ↑in
BPH, it is not specific (Stamey et al, 1987)
● PSA elevations in patients who undergo supposed curative
therapy are distressing (Frazier et al, 1993)
● PSA level alone does not facilitate precise pathologic staging.
Staging accuracy of PSA, can be enhanced by considering the
variables of tumour grade and clinical stage (Ruckle et al,
1994)
● High degree of variability between guidelines on what defines
biochemical failure, i.e., change in PSA that should prompt
further investigation (McIntosh et al, 2009)

37. Thank You!