Prostate Cancer Surgical Practice Guidelines

Scope and Format of Guidelines

The Society of Surgical Oncology surgical practice guidelines focuson the signs and symptoms of primary cancer, timely evaluation of the symptomaticpatient, appropriate preoperative evaluation for extent of disease, androle of the surgeon in diagnosis and treatment. Separate sections on adjuvanttherapy, follow-up programs, or management of recurrent cancer have beenintentionally omitted. Where appropriate, perioperative adjuvant combined-modalitytherapy is discussed under surgical management. Each guideline is presentedin minimal outline form as a delineation of therapeutic options.

Since the development of treatment protocols was not the specific aimof the Society, the extensive development cycle necessary to produce evidence-basedpractice guidelines did not apply. We used the broad clinical experienceresiding in the membership of the Society, under the direction of AlfredM. Cohen, md, Chief, Colorectal Service, Memorial Sloan-Kettering CancerCenter, to produce guidelines that were not likely to result in significantcontroversy.

Following each guideline is a brief narrative highlighting and expandingon selected sections of the guideline document, with a few relevant references.The current staging system for the site and approximate 5-year survivaldata are also included.

The Society does not suggest that these guidelines replace good medicaljudgment. That always comes first. We do believe that the family physician,as well as the health maintenance organization director, will appreciatethe provision of these guidelines as a reference for better patient care.

Society of Surgical Oncology Practice Guidelines:Prostate Cancer

Symptoms and Signs Early-stage disease

• Related to prostatism
• Diminished force of stream
• Frequency and urgency related to benign prostate hyperplasia (BPH)or prostate cancer
• Palpation for nodularity or firmness on digital rectal examination
• Routine prostate specific antigen (PSA) test more than 4 ng/mL
• Age-specific reference ranges have been suggested but have not provento be beneficial.

Advanced-stage disease

• Symptoms secondary to disseminated disease
• Pain
• Anemia
• Azotemia
• Above symptoms may cause shortness of breath, easy fatigability, orgeneralized debility.
• Signs are related to elevations in PSA and secondary alterations inserum alkaline phosphatase, especially isoenzymes.
• Other symptoms may be secondary to progressive obstructive diseasewith elevation in serum creatinine or blood urea nitrogen, and secondarymetabolic effects associated with azotemia.
• Further symptoms maybe related to widespread bone marrow replacement and secondary involvementof the bone marrow, particularly platelets and red cell count.
• Hematuria may be noted but is rare.

Evaluation of the Symptomatic Patient Work-up

• Previous health history or the previous studies obtained by the referringphysician
• PSA: normal range 0-4 ng/mL. Some authors have advocated age-relatedPSA values. PSA velocity more than 0.8 ng/mL per year is cause for concern.
• CBC and evaluation of renal function

Physical examination

• Include palpation of the abdomen and digital rectal examination.
• Transrectal ultrasound with biopsy is often utilized for patients withelevation of PSA alone.
• The major role of transrectal ultrasound is identification of hypoechoicareas and guidance of needle biopsies into different areas of the prostate.
• Cystoscopy may be indicated for hematuria.

Appropriate timeliness of surgical referral

• Depends upon the degree and severity of signs and symptoms, as wellas laboratory tests compatible with either localized or disseminated disease
• Reasonable interval for evaluation should be within 4 weeks.

Preoperative Evaluation for Extent of Disease Staging studies for localized disease

• Digital rectal examination
• Transrectal ultrasound
• Gleason sum of the biopsy specimen
• Number and percentage of cores involved with prostate cancer and levelof PSA
• For extracapsular disease involvement, include CT scan, which seemsto be useful predominantly for involvement of seminal vesicles, or endorectalsurface coil MRI.
• MRI seems to be the most accurate imaging study for local staging,although data with clinical surgical correlation are still accumulating.

Evaluation for metastatic disease

• Include a bone scan of the bony skeleton if PSA more than 8 ng/mL
• Regional lymph node involvement. CT scan is only modestly useful for the evaluation of the regional lymphnodes that lie in the obturator and external iliac chain.

Role of the Surgeon in Initial Management Evaluation of the symptomatic patient

• The surgeon is often involved in establishing the diagnosis of prostatecancer. Patients with a palpable nodule or elevated PSA generally undergotransrectal ultrasound, done either by a urologist or radiologist, withultrasound-directed needle biopsies using a spring-loaded biopsy gun.
• For patients with palpable nodules, digitally directed biopsies maybe utilized.
• For patients with hypoechoic areas seen on ultrasound, biopsies canbe directed through the hypoechoic area.
• For patients with elevated PSA but no palpable or visual abnormalities,six sector biopsies of the prostate are obtained. The surgeon generallyassumes the role of diagnostician to obtain selected staging studies asindicated, based on the patient's symptoms.

Diagnostic procedures

• Transrectal ultrasound-guided needle biopsies of the prostate

Surgical considerations

• Unilateral or bilateral nerve-sparing radical retropubic prostatectomy
• Radical perineal prostatectomy
• Lymphadenectomy via open or laparoscopic approach

Other therapeutic considerations

• External-beam radiation therapy
• Interstitial radiation therapy
• Hormonal manipulation
• Observation

These guidelines are copyrighted by the Society of Surgical Oncology(SSO). All rights reserved. These guidelines may not be reproduced in anyform without the express written permission of SSO. Requests for reprintsshould be sent to: James R. Slawny, Executive Director, Society of SurgicalOncology, 85 W Algonquin Road, Arlington Heights, IL 60005.

An estimated 317,100 new cases of prostate cancer were diagnosed inthe United States in 1996 with 41,400 concurrent deaths.[1] The most importantrisk factors for prostate cancer, as they are understood today, are a positivefamily history and being of the African-American race.[2] For this andother reasons, the American Cancer Society, American Urologic Association,American College of Radiology, and College of American Pathology all recommendan annual digital rectal examination and a prostate-specific antigen (PSA)blood test commencing at age 50.[2] However, for those with either of thetwo risk factors, annual testing is recommended beginning at age 40.[2]

The American Cancer Society has followed a cohort of men, age 55 yearsand older, since 1988, and based on these and other data, has determinedthat the tumors detected by early detection efforts are clinically significantand warrant treatment.[3-6]

In general, 0 to 4 ng/mL (Hybritech Tandem-R) is considered the normalrange for PSA.[5] Other applications of PSA evaluation include PSA density,PSA velocity, and age-related levels.[5] All of these, with the exceptionof the age-related levels, appear to offer some individual benefit withregard to increased sensitivity but at the expense of decreased specificity.[5,6]

Stage and Grade

Localized prostate cancer represents a spectrum of clinical stages fromT1a to T3 (Table 1). There are variationsin malignant potential within each stage.[6] The presence or absence oflymph node metastases is an important prognostic factor.[6] In general,there is a relationship among tumor grade, PSA, and lymph node status.[6-9]Most patients with a PSA less than 20 ng/mL and a Gleason grade less than7 are at low risk of lymph node metastases.[6-9] However, a poorly differentiated(Gleason sum 8) tumor with a PSA of 15 ng/mL may pose a 20% risk of nodaldisease.[6]

Treatment

Treatment should be considered for any man with prostate cancer whosesurvival, in the opinion of the clinician, will be shortened by the cancer.[6]Usually, these are men with a life expectancy of more than 10 years, inwhom treatment would be expected to influence outcome.[6] Treatment optionsshould be discussed with the patient, and, in some cases, second opinionsshould be sought from multiple specialists.

The list of therapeutic options includes the time-honored methods ofradical prostatectomy and radiation therapy, brachytherapy, as well aswatchful waiting, hormone manipulation, and cryotherapy. The major challengein choosing among these options is the lack of data from randomized clinicaltrials.[6]

Surgery

Since 1984, there has been a 2-1/2-fold increase in the rate of prostatecancer surgery (radical prostatectomy), chiefly as a result of the detectionof early-stage cancers with PSA and transrectal ultrasound-driven biopsies.[10]This increase is not excessive in light of the numbers of available casesin younger aged men.

Surgical mortality in community hospitals, as surveyed by the Commissionon Cancer of the American College of Surgeons, is under 1%, with totalincontinence rates of less than 3%.[11] Impotence rates are age- and stage-related.[6,11]For radical prostatectomy, if the malignancy is organ confined, long-termsurvival is indistinguishable from that in age-matched men without prostatecancer.[6] Rates of survival at 15 years in excess of 50% have been reported.[6]

Radiation Therapy

Reported results of radiotherapy for localized prostate cancer froma multi-institutional database over a 16-year period indicate that survivalof patients with T1, N0 disease is similar to a that of healthy age-matchedpopulation. Survival of T2, N0 patients was 22% lower than age-matchedcontrols. Survival of was 15% lower in T3-4, N0 patients than in T2, N0patients at 10 years but was identical at 16 years.[6,12]

Prospective data comparing impotence post-radiotherapy with the naturalevolution of sexual dysfunction are presently lacking.[6,13]

There is a renewed interest in brachytherapy (interstitial radiationtherapy) for prostate cancer based on recent promising results.[14] Brachytherapyshows evidence of achieving good local control and has a high degree ofpatient acceptance, with considerable cost-effectiveness and short hospitalstays.[14] Long-term (more than 10 years) results with brachytherapy, aswith cryotherapy, are not yet available.[6]

Watchful Waiting

Several reports have advocated watchful waiting for prostate cancerin small, carefully selected groups of patients over 70 years of age withlow-grade, low-volume tumors.[6,15,16] Watchful waiting implies treatmentfor progression. If palliative treatment only is planned, it may be arguedthat follow-up is not necessary.[6]

Medical Therapy

Once progression has been observed, cure is no longer possible in mostpatients. One exception may be progression from T1c to T2, which may stillbe curable.[6] Hormonal therapy provides a durable period of response witha good quality of life in most patients.[6]

New methods of follow-up for detection of occult soft-tissue disease,such as single-photon emission CT (SPECT) scintiscanning with CYT 356 antibody,may result in earlier treatments being instituted for measurable disease.[17,18]These may lead to changing survival statistics in this group of patients.[17,18]

The treatment of hormone-refractory disease remains selective but possible.[19]The active agents that are most frequently employed and can provide measurableand durable responses in significant numbers of patients are: estramustine(Emcyt), doxorubicin, platinum compounds, fluorouracil (with or withoutetoposide [VePesid]), and vinblastine.[19] Some new combinations, havebeen described by the National Prostate Cancer Project.

A new blood test that measures both poor-prognosis or hormone-refractorystates, the prostate-specific membrane antigen, has been described, andmay be useful in the long-term evaluation and follow-up of prostatic cancerpatients.[20]

References:

1. Cancer Facts & Figures--1996. Atlanta, American Cancer Society,1996.

2. Mettlin C, Jones G, Averette H, et al: Defining and updating theAmerican Cancer Society guidelines for the cancer-related check-up: Prostateand endometrial cancer. CA Cancer J Clin 43(1):42-46, 1993.

3. Murphy GP: Prostate cancer: Here and now. CA Cancer J Clin 45(3):133,1995.

4. Slawin KM, Ohori M, Dillioglugil O, et al: Screening for prostatecancer: An analysis of the early experience. CA Cancer J Clin 45(3):134-147,1995.

5. Brawer MK: How to use prostate-specific antigen in the early detectionor screening for prostatic carcinoma. CA Cancer J Clin 45(3):148-164, 1995.

6. Denis LJ, Murphy GP, Schröder FH: Report of the Consensus Workshopon Screening and Global Strategy for Prostate Cancer. Cancer 75(5):1187-1207,1995.

7. Partin AW, Yoo J, Carter HB, et al: The use of prostate specificantigen, clinical stage, and Gleason score to predict pathological stagein men with localized prostate cancer. J Urol 150:110-4, 1993.

8. Labrie F, Dupont A, Cusan L: Downstaging of localized prostate cancerby neoadjuvant therapy with flutamide and Lupron: The first controlledand randomized trial. Clin Invest Med 16:499-509, 1993.

9. Wolf LS Jr, Shinohara K, Carroll PR, et al: Combined role of transrectalultrasonography, Gleason score, and prostate-specific antigen in predictingorgan-confined prostate cancer. Urology 41:207-216, 1993.

10. Mettlin C, Murphy GP, Menck H: Trends in treatment of localizedprostate cancer by radical prostatectomy: Observations from the Commissionon Cancer National Cancer Database, 1985-1990. Urology 43(4):488-492, 1993.

11. Murphy GP, Mettlin C, Menck H, et al: National patterns of prostatecancer treatment by radical prostatectomy: Results of a survey by the AmericanCollege of Surgeons Commission on Cancer. J Urol 152(suppl):1817-1819,1994.

12. Hanks GE, Krall JM, Hanlon AL, et al: Patterns of care and RTOGstudies in prostate cancer: Long-term survival, hazard rate observations,and possibilities of cure. Int J Radiat Oncol Biol Phys 28:39-45, 1994.

13. Bagshaw MA, Kaplan ID, Cox R: Radiation therapy for localized disease.Cancer 71:939-52, 1993.

14. Porter AT, Blasko JC, Grimm PD, et al: Brachytherapy for prostatecancer. CA Cancer J Clin 45(3):165-178, 1995.

15. Johansson J, Adami A, Andersson S, et al: High 10 year survivalrate in patients with early, untreated prostate cancer. JAMA 267:2191-6,1992.

16. Whitmore WF, Warner JA, Thompson IM: expectant management of localizedprostatic cancer. Cancer 67:1091-1096, 1991.

17. Wynant GE, Murphy GP, Horoszewicz JD, et al: Immunoscintigraphyof prostatic cancer: Preliminary results with 111In-labeled monoclonalantibody 7E11.C5.3 (CYT-356). Prostate 18(3):229-241, 1991.

18. Murphy GP: Radioscintiscanning of prostate cancer. Cancer 75(7;suppl):1819-1822, 1995.

19. Murphy GP: Follow-up evaluation of National Prostatic Cancer Projectprotocols and other studies. Urology 44(6A):61-66, 1994.

20. Murphy GP, Holmes EH, Boynton AL, et al: Comparison of prostatespecific antigen, prostate specific membrane antigen, and LNCaP-based enzyme-linkedimmunosorbent assays in prostatic cancer patients and patients with benignprostatic enlargement. Prostate 26(3):164-168, 1995.