ACR Appropriateness Criteria®
Clinical Condition: Node-Positive Prostate Cancer
Variant 1: 72-year-old male. Microscopic metastasis in a single lymph node following radical prostatectomy. Negative margins.
Treatment |
Appropriateness Rating |
Comments |
Radiation therapy with hormonal treatment |
7 |
|
Hormonal treatment alone |
6 |
|
Radiation to pelvis and prostate bed |
5 |
|
Radiation to prostate bed only |
2 |
|
Pelvic Radiation Dose |
4500/25 fractions
|
6 |
|
5040/28 fractions
|
7 |
|
5400/30 fractions
|
2 |
|
Prostate Bed Dose |
4500/25 fractions
|
2 |
|
5940/33 fractions
|
6 |
|
6660/37 fractions
|
7 |
|
Treatment Plan |
3D CT-based plan
|
7 |
|
IMRT
|
7 |
|
2D CT-based plan
|
6 |
|
Non-CT based computerized plan
|
5 |
|
Blocking |
Complex block
|
6 |
|
Hand block
|
5 |
|
Open field
|
3 |
|
Appropriateness Criteria Scale
1 2 3 4 5 6 7 8 9
1 = Least appropriate 9 = Most appropriate
|
Note: Abbreviations used in the tables are listed at the end of the "Major Recommendations" field.
Variant 2: 55-year-old male. Grossly involved pelvic lymph nodes before planned prostatectomy.
Treatment |
Appropriateness Rating |
Comments |
Radiation therapy with hormonal treatment |
7 |
|
Hormonal treatment alone |
6 |
|
Radiation to pelvis and prostate |
6 |
|
Radical prostatectomy with hormonal treatment |
3 |
|
Radical prostatectomy alone |
2 |
|
Radiation to prostate only |
2 |
|
Pelvic Radiation Dose |
4500/25 fractions
|
6 |
|
5040/28 fractions
|
7 |
|
5400/30 fractions
|
2 |
Additional radiation boost to the area of the involved lymph nodes is acceptable |
Prostate Dose |
7020/39 fractions
|
7 |
|
7560/42 fractions
|
7 |
|
5940/33 fractions
|
2 |
|
6660/37 fractions
|
6 |
|
Treatment Plan |
IMRT
|
7 |
|
2D CT-based plan
|
6 |
|
3D CT-based plan
|
5 |
|
Non-CT based computerized plan
|
4 |
|
Blocking |
Complex block
|
6 |
|
Hand block
|
5 |
|
Open field
|
2 |
|
Appropriateness Criteria Scale
1 2 3 4 5 6 7 8 9
1 = Least appropriate 9 = Most appropriate
|
Note: Abbreviations used in the tables are listed at the end of the "Major Recommendations" field.
Variant 3: 67-year-old male. PSA of 30. CT-guided fine needle biopsy of pelvic lymph node reveals metastatic adenocarcinoma.
Treatment |
Appropriateness Rating |
Comments |
Radiation therapy with hormonal treatment |
8 |
|
Radiation to pelvis and prostate |
7 |
|
Hormonal treatment alone |
6 |
|
Radical prostatectomy with hormonal treatment |
3 |
|
Radical prostatectomy alone |
2 |
|
Radiation to prostate only |
2 |
|
Pelvic Radiation Dose |
4500/25 fractions
|
6 |
|
5040/28 fractions
|
7 |
|
5400/30 fractions
|
2 |
Additional radiation boost to the area of the involved lymph nodes is acceptable. |
Prostate Dose |
5940/33 fractions
|
2 |
|
6660/37 fractions
|
6 |
|
7020/39 fractions
|
7 |
|
7560/42 fractions
|
7 |
Still needs local control, could give higher dose. |
Treatment Plan |
3D CT-based plan
|
7 |
|
IMRT
|
7 |
|
2D CT-based plan
|
6 |
|
Non-CT based computerized plan
|
4 |
|
Blocking |
Complex block
|
8 |
|
Hand block
|
6 |
|
Open field
|
2 |
|
Appropriateness Criteria Scale
1 2 3 4 5 6 7 8 9
1 = Least appropriate 9 = Most appropriate
|
Note: Abbreviations used in the tables are listed at the end of the "Major Recommendations" field.
Histologically proven lymph node metastasis from adenocarcinoma of the prostate portends a poor prognosis. With the widespread use of PSA screening, 90% of all prostate cancers are discovered in the local and regional stages. Thus approximately 10%-20% of patients present with locally advanced disease, many of whom have positive regional lymph nodes. The optimal treatment of these node-positive patients remains controversial; recommendations range from immediate hormonal treatment to aggressive combined modality approaches.
Given the variable natural history of prostate cancer, several investigators have examined histologic variables that can predict ultimate prognosis. Recent investigations have examined immunohistochemical variables (p53 alterations, human glandular kallikrein 2) that are detectable in metastatic lymph nodes as potential prognostic factors. The available data indicate that both the number of involved nodes and the extent of metastatic involvement are predictive of subsequent disease progression. The few series with long follow-up, however, indicate that even patients with minimal microscopic lymphatic metastases have poor long-term disease-free survival with most patients developing metastatic disease by 10 years following treatment.
In the absence of some form of adjuvant hormonal therapy, radical local or locoregional therapy (radical prostatectomy plus lymph node dissection or radiotherapy) has resulted in ten-year survivals of only 20%-30% with nearly all patients developing evidence of distant metastasis within ten years of diagnosis. Series of patients treated with early androgen ablation show similar results. The best results reported in node-positive patients are from series that combined a local or locoregional modality (surgery or radiation) with early adjuvant hormonal therapy.
Many of the series reported above include patients treated before the widespread availability of PSA to monitor patients following treatment. The few series for which post-treatment PSA levels are available show much lower rates of disease-free survival if PSA is used to define the absence of disease.
A randomized trial found an overall survival benefit for immediate androgen deprivation following prostatectomy for men with node-positive disease. This study was rather small (98 men), never achieved its projected goal of 240 men, and did not require central pathologic review. Furthermore, disease-free survival in the control arm was lower than that reported in several single-institution series of radical prostatectomy alone. Although this study suggests an advantage for early androgen-deprivation, further studies with larger numbers of patients will be required. Two other prospective randomized series of node-positive prostate cancer patients have been reported recently. In the first study, the subset of pathologically positive lymph node patients showed a clear overall survival advantage with the addition of hormone therapy to definitive radiation therapy. In the data from the first study, the subset of pathologically positive lymph node patients showed a clear overall survival advantage with the addition of hormone therapy to definitive radiation therapy. Each endpoint from PSA—local control, distant disease, cause specific, and overall survival was positively impacted by the use of hormone therapy over radiation alone for the node—positive patients in that trial. In addition, the second study, for which patients were randomized between whole pelvic and prostate only irradiation in addition to neoadjuvant vs adjuvant therapy, showed an advantage to patients with whole pelvis radiation therapy and neoadjuvant hormonal manipulation in terms of progression-free survival for patients who had a risk of lymph node involvement >15%.
The natural history of treated patients with node-positive prostate cancer indicates that a large proportion of men will develop distant metastases by within ten years of treatment. Recent molecular staging methods suggest that a majority of patients with node-positive prostate cancer harbor occult distant metastatic disease at the time of diagnosis. One author has published his experience in 55 men with prostate cancer in whom bone aspirates were examined by reverse transcriptase polymerase chain reaction (RTPCR) and immunohistochemical techniques to identify metastatic prostate cancer cells. It was reported that more than 70% of men with lymphatic metastases and a negative bone scan had evidence of metastatic cancer cells in the bone marrow.
If these node-positive patients do in fact have micrometastatic distant disease, any local modality is doomed to failure. Treatment strategies designed to cure patients with node-positive prostate cancer should include a systemic component in addition to aggressive locoregional therapy.
Recent studies suggest that comprehensive pelvic nodal radiotherapy may be best accomplished by using IMRT. This approach results in better coverage of nodal areas and less dose to adjacent tissues such as the bladder, rectum, and penis.
Abbreviations
- 2D-CT two-dimensional computed tomography based plan
- 3D-CT, three-dimensional computed tomography based plan
- CT, computed tomography
- IMRT, intensity modulated radiotherapy
- PSA, prostate-specific antigen