radical prostatectomy in high serum psa values a surgical expertise against

Radical Prostatectomy (RP) in Patients with High Serum

PSA values - A Surgical Expertise

Views Against..Vijay Elipay

Asst Manager, Med Info Services

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.

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

RP can be done in different ways

●Open approaches▪Radical retropubic prostatectomy (RRP)▪Radical perineal prostatectomy

●Laparoscopic approaches▪Laparoscopic RP ▪Robotic-assisted laparoscopic RP

Open approaches to RP

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

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.


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


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.


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.


History of Prostate-specific Antigen (PSA)

Characteristics of men, number of patients (percentage), undergoing RP at Johns Hopkins Hospital

Characteristic 2006-2011 200-2005

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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

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



Preoperative serum concentration of PSA in relation to cancer volume in 45 patients undergoing consecutive RP (log-log plot)



PSA, TAP and PAP after radical prostatectomy

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.


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?

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

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

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.

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

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.

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.


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.


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

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


Follow-up care for men with prostate cancer and the role of primary care: a systematic review of international guidelinesGuidelines follow-up recommendations on PSA testing


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 andRecommendations (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

Follow-up care for men with prostate cancer and the role of primary care: a systematic review of international guidelines


● 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

Radical Prostatectomy: Biochemical RelapseFactors Associated with Metastatic Disease and Death

●Persistently elevated PSA after Prostatectomy

●Shorter interval from surgery to biochemical relapse

●Shorter PSA doubling time

Radical Prostatectomy GPSM Scoring AlgorithmGPSM – 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

GPSM Scoring Outcomes

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

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

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

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)

Thank You!

radical prostatectomy in high serum psa values a surgical expertise against

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