CHAPTER 47 Treatment of Locally Advanced or Recurrent Prostate Cancer
What is the definition of locally advanced prostate cancer?
Clinically detectable locally advanced prostate cancer includes cases with clear evidence or a high likelihood of cancer extension beyond the prostate capsule into the periprostatic tissue (T3a), involvement of the seminal vesicles (T3b), or involvement of adjacent organs (T4). Patients with locally advanced disease also are at higher risk of regional (lymph node) or distant (bone) metastases. For patients treated with radical prostatectomy, histological evidence of extraprostatic extension and surgical margin status are used to define locally advanced disease.
How is locally advanced prostate cancer diagnosed?
Historically, the identification of patients with locally advanced prostate cancer has been based on clinical examination (digital rectal examination, DRE) and/or CT scan demonstrating clinical stage T3 or T4. Clinical surrogates have been used to identify patients who are “likely” to harbor locally advanced disease including PSA >20 ng/mL and/or Gleason score ≥8. The term “high-risk cancer” may encompass those with evidence of or a high likelihood of locally advanced disease.
How do you estimate the likelihood of having a locally advanced disease?
Clinical examination (DRE) alone can be quite subjective and imaging such as ultrasound or CT scans lack the resolution to provide sufficient accuracy in predicting locally advanced disease, especially when its microscopic. Due to its improved resolution MRI for staging has been expanding especially since 2T and 3T scanners with surface coils (as opposed to endorectal coils) have become more readily available. Several risk assessment tools have been developed over the last 10 years to predict the likelihood of locally advanced disease. The tools (tables, nomograms, neural networks, etc) incorporate several clinical variables, such as clinical stage, PSA, biopsy Gleason score, and biopsy cores with cancers, to predict locally advanced or high-risk cancer. Most of these tools, that are now available online, tend to provide a more accurate risk-assessment than any individual parameter alone.
What is the incidence of locally advanced prostate cancer and how has it changed over the last 2 decades?
The incidence of clinical stage T3-4 has decreased from 11.8% to 3.5% over the last 15 to 20 years. This reduction is thought to be largely due to the use of the PSA test for early detection of prostate cancer.
What is the incidence of pathological T3 disease in patients who are initially treated with radical prostatectomy for clinically localized prostate cancer?
The incidence of pathological extraprostatic disease has decreased from nearly 40% (1983-1991) to 31% (1992-2003). In a recent surgical series (2008), the incidence of T3a was 13.8% and T3b was 5.7%. This may in part be due to the use of careful selection criteria and risk stratification before surgery. Further, the extent of extraprostatic cancer in the contemporary (PSA) era is often focal and microscopic as opposed to large multifocal areas of extraprostatic disease noted in the earlier series.
What is the extent of clinical staging error for locally advanced prostate cancer?
Clinical over staging occurs in up to 7% to 20% of patients who are subsequently found to have organ-confined prostate cancer. Under staging has been reported in 20% to 35% of patients who are found to have T3-4 lesions or microscopic nodal metastases, depending upon the criteria used to select surgical candidates.
Does PSA level reliably predict pathological stage?
Up to 70% of patients with locally advanced prostate cancer may have a serum PSA level of >10 ng/mL, but serum PSA level alone cannot reliably predict pathological stage.
What are the pitfalls of seminal vesicle biopsies to assess local tumor extent in patients suspected of harboring locally advanced prostate cancer?
A significant number of false-negative biopsy results can occur due to sampling error in the presence of focal or microscopic seminal vesicle invasion (SVI). Even when biopsies are performed due to clinical suspicions of SVI, only 50% of patients will have positive biopsy results. False-positive results can occur because of a drag-through artifact where the needle goes through the base of the prostate. Due to architectural similarities between SV and low-grade cancers or benign glands, the diagnosis can sometimes be challenging, resulting in false-positive SV biopsy. Lipofuscin staining can identify seminal vesicle tissue and help minimize the false-positive results.
What percentage of patients with locally advanced prostate cancer will require surgical or medical intervention for disease progression if initially placed on watchful waiting?
Over 70% will require some form of intervention secondary to local or distant disease progression depending upon the length of follow-up and life expectancy of the patient. Depending upon the extent of disease progression, most patients are treated with hormonal ablation therapy or with radiation therapy plus hormonal ablation therapy. If initially left untreated, up to 50% of patients may need transurethral resection of the prostate (TURP) for obstruction or hematuria or nephrostomy tube placement for ureteral obstruction.
A 67-year-old patient presents with Gleason score 9, clinical stage T2b, N0, M0 prostate cancer. After a lengthy discussion of treatment options, the patient decides to pursue initial observation. What are the disease-specific and metastasis-free survival rates at 10 years for patients with high-grade, clinically localized prostate cancers that are managed with watchful waiting?
Patients with clinically localized (clinical stage ≤T2) high-grade prostate cancer who are treated conservatively will have a disease-specific survival rate of only 34% at 10 years, and only 26% of these patients will be free of metastasis at 10 years. Patients with high-grade prostate cancers are over 6 times more likely to die of prostate cancer than are patients with low-grade tumors.
What is the survival of patients with locally advanced disease for 5, 10, and 15 years without immediate or early treatment?
Overall survival is reported from 25% to 92% at 5 years and 14% to 78% at 10 years for patients who harbor cancers of high Gleason grade or stage who are treated only when clinical disease progression is noted. Of all patients with locally advanced prostate cancer, 15-year mortality rates of 6%, 17%, and 56% are noted for well-differentiated, moderately differentiated and poorly differentiated tumors, respectively.
What is the incidence of SVI when performing radical retropubic prostatectomy in patients with clinical T3a disease?
Approximately 5% to 15% of patients will have SVI after radical prostatectomy.
What are the long-term results following radical prostatectomy for clinical T3 disease without adjuvant therapy?
Cancer-specific survival rates are 85% to 92% and 79% to 82% at 5 and 10 years, respectively, regardless of adjuvant therapy. However, without any adjuvant treatment, biochemical (PSA) relapse is noted in about 50% of men by 5 years.
What is the PSA relapse-free survival patients undergoing radical prostatectomy for clinically localized disease that are noted to have pathological T3 disease?
The 5-year PSA relapse-free survival is 76% for PT3a, 37% for PT3b, and 18% for node positive men after radical prostatectomy for clinically localized disease.
What is the role of adjuvant radiation therapy in pathological T3 disease?
It has been shown in 2 RCT (EORTC 22911 and SWOG 8794) that adjuvant RT leads to improved biochemical-free survival, from 50% to 88% at 5 years. This appears to be an improvement (30%-50%) compared with the results of surgery alone in high-risk patients. In EORTC 22911, immediate RT was associated with improved biochemical relapse-free survival (74% vs 53% without RT, P < 0.001) at 5 years. Similarly, SWOG 8794, with 10.6 years median follow-up, supported immediate RT with a nearly 50% reduction in biochemical recurrence (BCR; 35% vs 64% without RT, P < 0.001). In addition, both metastasis-free and overall survival were improved with adjuvant RT (HR, 0.71 and 0.72, respectively).
Which subgroups of pT3 patients may benefit the most with adjuvant RT after radical prostatectomy?
Men with SVI who achieve a low PSA level (<0.3 ng/mL) after prostatectomy or those positive surgical margins may be a more favorable group in whom adjuvant RT may be considered.
A 60-year-old man presents with palpable extracapsular extension, PSA 15 ng/mL, and Gleason score 7 prostate cancer. He inquires about the use of androgen suppression therapy for few months prior to radical prostatectomy. Is there any evidence that neoadjuvant hormonal therapy results in downstaging of clinical stage T3 prostate cancer?
There have been many studies of neoadjuvant hormonal therapy in patients with clinical stage T3 disease. These studies showed a drop in PSA level in more than 90% of cases, with a 30% to 50% decrease in prostate volume after neoadjuvant hormonal therapy. However, only about 21% of these patients had organ-confined disease, which is not substantially different from the frequency of organ-confined disease noted in patients undergoing surgery without neoadjuvant hormonal therapy for stage T3 disease. Thus, there is no clear evidence to support the use of neoadjuvant hormonal therapy for downstaging of T3 prostate cancer.
The use of neoadjuvant hormonal therapy prior to radical prostatectomy has been shown to reduce the risk of positive surgical margins in which patients?
In clinically localized (T2) cancers, there was decrease in the rate of positive surgical margins. For locally advanced tumors (specifically cT3), current data, both retrospective and prospective, do not support a significant benefit of neoadjuvant androgen ablation before surgery.
Is there any proven reduction in the rate of biochemical failure for patients treated with 3 months of neoadjuvant hormonal therapy prior to radical prostatectomy?
There is no overall benefit of short-term neoadjuvant therapy as measured by BCR (34%-38%), regardless of the clinical stage or any reduction in the positive margin rate. The use of long-term (neoadjuvant and adjuvant) androgen suppression with radical prostatectomy has not been studied systematically.
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
