112
Management of Localized Prostate
Cancer
William J. Catalona; Misop Han
Questions
1.Prostate cancer is the cause of mortality in what percentage of U.S. men?
a.1%
b.3%
c.10%
d.16%
e.30%
2.An outcome comparison between different treatment modalities for localized prostate cancer is difficult because:
a.most patients diagnosed with prostate cancer receive the same treatment.
b.outcome measures are similar.
c.the treatment outcomes in any patient series may be influenced by the malignant potential of the tumors as well as the treatment used.
d.there are many effective treatments for clinically localized prostate cancer.
e.randomized clinical trials eliminate selection bias.
3.Which statement is the best rationale for active surveillance protocols for localized prostate cancer?
a.A prospective, randomized clinical trial demonstrated similar local cancer progression and metastasis rates for patients with clinically localized prostate cancer managed with deferred treatment and radical prostatectomy.
b.In most active surveillance studies, only approximately 15% of patients develop objective evidence of tumor progression within 5 years.
c.An accurate assessment of clinically insignificant or indolent cancers is determined by biopsy results.
d.Active surveillance allows timely intervention as long as patients with localized prostate cancer are followed up semiannually with digital rectal examination and prostate-specific antigen (PSA) levels.
e.The potential benefits of surgery do not outweigh potential complications in men with a life expectancy of less than 10 years and a low-grade prostate cancer.
4.What is an appropriate criterion used for recommending intervention during active surveillance for prostate cancer?
a.PSA velocity less than 0.5 ng/mL/year
b.More than 10% of a biopsy core involvement
c.Previous cryotherapy of the prostate gland
d.Gleason pattern 4 or 5 present
e.Any positive repeat biopsy
5.What recent innovation has been most responsible for the wider use of radical prostatectomy?
a.Discovery that the pudendal nerves are responsible for urinary continence
b.Preservation of the external sphincter muscle that yields urinary continence rates in excess of 90%
c.Frequent use of saturation biopsy under general anesthesia
d.Magnification provided by robotic-assisted prostatectomy
e.Elimination of pelvic lymphadenectomy in patients with low-risk tumor features
6.What features correctly characterize each of the following radical prostatectomy approaches?
a.Perineal: more blood loss and a longer operative time than the retropubic approach
b.Retropubic: higher risk for rectal injury and postoperative fecal incontinence
c.Laparoscopic: lowest complication rate
d.Laparoscopic: lowest positive surgical margin rate
e.Robotic: less blood loss due to the pneumoperitoneum
7.What outcome do the Partin tables predict?
a.Clinical stage
b.Gleason score
c.Pathologic stage
d.Biochemical recurrence-free probability
e.Cancer-specific survival probability
8.During the nerve-sparing portion of radical retropubic prostatectomy, the best approach is to:
a.dissect the neurovascular bundles free of the posterolateral surface of the prostate gland.
b.use bipolar electrocautery to transect the urethra.
c.perform a retrograde dissection to identify the vas deferens.
d.release the endopelvic fascia after the neurovascular bundle dissection.
e.use a harmonic scalpel to release neurovascular bundles.
9.Which of the following is most closely associated with urinary continence recovery following radical retropubic prostatectomy?
a.Preoperative renal function
b.Pathologic tumor stage
c.Performance of nerve-sparing surgery
d.Patient age
e.Bladder neck-sparing dissection
.The return of erectile function following radical retropubic prostatectomy correlates best with:
a.absence of preoperative hormonal therapy.
b.absence of postoperative radiation therapy.
c.absence of antihypertensive therapy.
d.absence of a smoking history.
e.nerve-sparing status.
.Which statement is TRUE of "PSA bounce"?
a.It is strongly associated with an intermittent androgen ablation therapy.
b.It usually occurs within 2 years of radiation therapy.
c.It should be treated immediately with combined androgen blockage therapy.
d.It is more commonly associated with external beam radiation therapy.
e.It does not exceed an increase of 2 ng/mL following radiation therapy.
.What is the ASTRO (American Society of Therapeutic Radiation Oncology) definition for recurrence following radiation therapy?
a.Three consecutive increases in PSA following radiation therapy, and back-dates the time of cancer progression to halfway between the second and third increase in PSA levels.
b.Three consecutive increases in PSA following radiation therapy with at least one PSA bounce.
c.Three PSA increases measured 12 months apart, and back-dates the time of cancer progression to halfway between the first and the second increase in PSA levels.
d.Three consecutive PSA increases measured 6 months apart, and backdates the time of cancer progression to halfway between the PSA nadir and the first rising PSA level.
e.Three consecutive PSA increases of total 2 ng/mL after reaching a PSA nadir.
.Which of the following criteria is a relative contraindication to external beam radiation therapy to the prostate?
a.Previous radical retropubic prostatectomy
b.Lower urinary tract symptoms
c.Previous transurethral resection of prostate (TURP)
d.Serum PSA less than 2 ng/mL
e.History of hematospermia
.Which of the following parameters is most predictive of favorable response to postoperative salvage radiation therapy?
a.Preoperative PSA less than 10 ng/mL
b.Extracapsular tumor extension
c.PSA doubling time of more than 3 months
d.Positive surgical margin
e.Preradiation PSA greater than 2 ng/mL
.Which of the following parameters is most associated with improved prostate cancer-specific survival with salvage radiotherapy for recurrence after surgery?
a.PSA doubling time of less than 6 months
b.Concurrent hormonal therapy
c.Lymph node metastasis
d.Initiation of salvage radiotherapy after PSA has risen above 2 ng/mL
e.Previous robot-assisted laparoscopic prostatectomy
Answers
1.b. 3%. About 1 in 7 men are diagnosed with prostate cancer during their lifetime. Because of effective treatment of some prostate cancers and the
biological indolence relative to the life expectancy of others, only about 16% of men diagnosed with prostate cancer ultimately die of it. As a result, prostate cancer is the cause of death in about 3% of the U.S. male population
2.c. The treatment outcomes in any patient series may be influenced by the malignant potential of the tumors as well as the treatment used. Patients whose tumor has a low malignant potential are predetermined to fare better with most treatments. Therefore, the treatment outcomes in any patient series may be influenced by the malignant potential of the tumors and also by the treatment used. Accordingly, it is difficult to compare the results of different reports, because the patient populations usually are not strictly comparable.
3.e. The potential benefits of surgery do not outweigh potential complications of surgery in men with a life expectancy of less than 10 years and a low-grade prostate cancer. Traditionally, watchful waiting has been reserved for men with a life expectancy of less than 10 years and a lowgrade (Gleason score 2 to 5) prostate cancer. However, active surveillance is now being studied in younger patients with low-volume, low-or intermediategrade tumors to avoid or delay treatment that might not be immediately necessary.
4.d. Gleason pattern 4 or 5 present. During active surveillance, intervention is recommended if Gleason pattern 4 or 5 is present, more than two biopsy cores are involved, or more than 50% of a biopsy core is involved. Progression is more likely in patients who have cancer present on every biopsy procedure.
5.b. Preservation of the external sphincter muscle that yields urinary continence rates in excess of 90%. Recent innovations that have led to the wider use of radical prostatectomy include (1) the development of the anatomic radical retropubic prostatectomy, which allows the dissection to be performed with good visualization and preservation of the cavernosal nerves responsible for erectile function and preservation of the external sphincter muscle that yields urinary continence rates in excess of 90%; (2) the development of extended ultrasound-guided biopsy regimens, performed under local anesthesia as an office procedure; and (3) the widespread use of PSA testing, which has led to the great majority of patients being diagnosed with clinically localized disease.
6.e. Robotic: less blood loss due to the pneumoperitoneum. Remotely controlled, robot-assisted laparoscopic surgery recently has become popular because of its greater technical ease for the surgeon, especially for tying
sutures and performing the vesicourethral anastomosis. Less blood loss due to the pneumoperitoneum is also an advantage over open surgical techniques.
7.c. Pathologic stage. Because imaging studies are not accurate for staging prostate cancer, preoperative clinical and pathologic parameters are used in the Partin tables to predict the pathologic stage, and thus identify patients most likely to benefit from the operation.
8.a. Dissect the neurovascular bundles free of the posterolateral surface of the prostate gland. Meticulous dissection is required to preserve the neurovascular bundles during the nerve-sparing radical retropubic prostatectomy. In performing nerve-sparing surgery, the neurovascular bundles are identified at the apex of the prostate, and the bundles are dissected free of the posterolateral surface of the prostate gland.
9.d. Patient age. The return of urinary continence following radical retropubic prostatectomy is strongly associated with patient age: more than 95% of men younger than 50 years are continent following surgery; 85% of men older than 70 years regain complete continence.
.e. Nerve-sparing status. The return of erectile function following radical retropubic prostatectomy correlates with the age of the patient, preoperative potency status, extent of nerve-sparing surgery, and the era of surgery.
.b. It usually occurs within 2 years of radiation therapy. Inflammation in the prostate gland can produce transient PSA elevation, called a PSA "bounce," following radiation therapy. PSA bounce usually occurs during the first 2 years after treatment and is less common with external beam therapy than with brachytherapy
.d. Three consecutive PSA increases measured 6 months apart, and backdates the time of cancer progression to halfway between the PSA nadir and the first rising PSA level. Until recently, the most frequent used definition for recurrence following radiation therapy was the American Society of Therapeutic Radiation Oncology (ASTRO) definition. It requires three consecutive PSA increases measured 6 months apart and back-dates the time of cancer progression to halfway between the PSA nadir and the first rising PSA level. Thus, it usually takes years to determine whether progression has occurred after radiotherapy.
In recent years, the Phoenix definition was proposed to replace the ASTRO definition. It eliminates back-dating but requires the PSA level to rise by 2 ng/mL before treatment failure is declared. Thus, the time to
recurrence is further prolonged after the PSA level begins to rise, and often it takes a considerably longer time for the PSA level to increase by 2 ng/mL. In some instances, adjuvant hormone therapy may be initiated before the PSA rises to 2 ng/mL. In practice, the Phoenix definition can yield results that are even more favorable than those obtained with the ASTRO definition.
.c. Previous transurethral resection of prostate (TURP). A prior transurethral resection of the prostate is a relative contraindication to brachytherapy and external beam radiation therapy because the prostate does not hold the seeds well, and radiation after transurethral resection of the prostate is associated with an increased risk for urethral stricture.
The presence of severe obstructive urinary symptoms is also a relative contraindication because of the risk for acute urinary retention, which is an
even greater risk in patients treated with brachytherapy. Another relative contraindication is inflammatory bowel disease.
.d. Positive surgical margin. Adjuvant radiotherapy is most likely to benefit patients with positive surgical margins or extracapsular tumor extension without seminal vesicle invasion or lymph node involvement. However, not all patients with extracapsular tumor extension or positive margins have tumor recurrence without radiotherapy, and most patients with highly adverse findings have treatment failure with distant metastases, despite adjuvant radiotherapy.
.a. PSA doubling time of less than 6 months. Trock et al reported on a retrospective study of men with PSA failure after radical prostatectomy that is unique in that patients received either no treatment, salvage radiation therapy, or salvage radiation therapy with androgen-deprivation therapy. They reported that salvage radiation was associated with a threefold reduction in prostate cancer mortality, and although the addition of hormone therapy provided no additional decrease in the risk for mortality, the patients who received hormone therapy had higher-risk disease. Therefore, hormone therapy probably provided additional benefit for these high-risk patients. The benefit was strongest in those with the shortest PSA doubling times.
Chapter review
1.Approximately 81% of prostate cancer cases detected appear to be localized at the time of detection. Only 4% of patients present with metastatic disease at the time of diagnosis.
2.Patients who have greater than a 10-year life expectancy and may be
considered for active surveillance should have low-volume disease, lowor intermediate-grade tumors (up to Gleason 3 + 4 = 7), nonpalpable lesions, and PSAs that are below 10. Many would suggest that any Gleason grade of 4 or 5 on biopsy makes the patient ineligible for active observation.
3.Patients who are actively observed should routinely have an interval biopsy. Follow-up biopsies in which no cancer is detected significantly decrease the risk of progression in these patients. Intervention is recommended if Gleason pattern 4 or 5 is present, more than two biopsy cores are involved, or more than 50% of a biopsy core is involved. Progression is more likely in patients who have cancer present on every biopsy procedure.
4.Approximately 25% to 50% of patients who choose active observation develop objective evidence of tumor progression within 5 years.
5.The median time from PSA failure to the development of metastatic disease after radical prostatectomy is 8 years, and from the time of metastases to death is 5 years. Thus there is a total of 13 years following detectable PSA after radical prostatectomy before death due to prostate cancer usually occurs. Moreover, only one third of the patients with detectable PSAs will develop clinical metastases.
6.Neoadjuvant hormone therapy does not enhance the resectability of prostate cancer in those patients undergoing a radical prostatectomy.
7.Bone scan, computed tomography (CT) scan, and magnetic resonance imaging (MRI) are not indicated preoperatively in patients with a Gleason score less than 7, a PSA less than 10 ng/mL, nonpalpable disease, and lack of extensive involvement of the majority of the cores.
8.Possible overdiagnosis of insignificant cancer occurs in 6% to 20% of radical prostatectomy specimens.
9.Adverse prognostic factors following radical prostatectomy include non– organ-confined disease, lymphovascular invasion, seminal vesicle invasion, extracapsular tumor extension, positive surgical margins, and lymph node metastases.
10.In those instances of high-grade adenocarcinomas and neuroendocrine tumors that do not produce much PSA, recurrent disease may be diagnosed by palpation, thus indicating a role for digital rectal exam (DRE) in monitoring.
11.The most common late complications of radical prostatectomy are
erectile dysfunction, urinary incontinence, inguinal hernia, and urethral stricture.
12.Intensity-modulated radiation therapy (IMRT) generally delivers in excess of 75 Gy.
13.Side effects of external beam radiation therapy include 5% to 10% persistent irritable bowel symptoms and 10% to 15% intermittent rectal bleeding. Approximately half of patients will be impotent.
14.Patients who have high-volume disease or high Gleason scores benefit from androgen-deprivation therapy before administering radiation therapy.
15.Brachytherapy with either iodine-125 or palladium-103 delivers 125 to 145 Gy to the prostate; it is seldom used in prostates which exceed 60 grams and those with high Gleason scores.
16.Not all patients with extracapsular tumor extension or positive surgical margins have a PSA failure. Those patients would not be expected to benefit from adjuvant radiation therapy.
17.There is no compelling evidence that an extensive pelvic lymphadenectomy is more beneficial than a standard lymphadenectomy when indicated.
18.In those who maintain erectile function following radical prostatectomy, the erection is generally less firm than it was preoperatively.
19.Only approximately one-third of patients who have a biochemical recurrence following radical prostatectomy will develop metastases.
20.Most patients with positive surgical margins are cured by the radical prostatectomy.
21.Following radiation therapy, inflammation in the prostate gland can produce transient PSA elevation, called a PSA "bounce." PSA bounce usually occurs during the first 2 years after treatment and is less common with external beam therapy than with brachytherapy.
22.Following radiation therapy, a meaningful elevation in PSA has several definitions: The ASTRO definition requires three consecutive PSA increases measured 6 months apart and back-dates the time of cancer progression to halfway between the PSA nadir and the first rising PSA level. The Phoenix definition was proposed to replace the ASTRO definition. It eliminates back-dating but requires the PSA level to rise by 2 ng/mL before treatment failure is declared. Thus it may take years to determine whether progression has occurred after radiotherapy.
23.A prior transurethral resection of the prostate is a relative contraindication to brachytherapy.
24.The role of adjuvant radiotherapy following radical prostatectomy is controversial because not all patients with extracapsular tumor extension or positive margins have tumor recurrence without radiotherapy, and most patients with highly adverse findings have treatment failure with distant metastases, despite adjuvant radiotherapy.