Prostate Cancer - Rising Psa

Front 1

Should a patient that has undergone radiation therapy for local treatment have an undetectable PSA?

Back 1

By contrast,
patients who have received external beam radiation therapy or brachytherapy, alone or in combination, have an intact although irradiated gland in place that may produce low levels of PSA that are not indicative of a treatment failure.

Front 2

Can there be a detectable PSA after radical prostatectomy that is not cancer? What PSA level is used as evidence of biochemical recurrence after radical prostatectomy?

Back 2

As noted, post-prostatectomy patients may have very low levels of PSA that can represent benign glands at the surgical margin, and as a result there is debate as to what precise level of PSA represents treatment failure definitively. Commonly discussed ranges that signify PSA failure are ≥0.2 or ≥0.4 ng/mL, although some authors have recognized that levels as low as 0.01 to 0.07 ng/dL can also represent failure.

Nevertheless, most clinicians accept that a PSA level of 0.4 ng/mL or higher that is rising represents treatment failure on the basis of follow-up studies showing that PSA values above this level do not plateau. Therefore, by consensus (Scher et al, 2004), a patient is considered to have progressed after a radical prostatectomy if the PSA level is 0.4 ng/mL or higher 8 weeks or more after the procedure and rises on a subsequent measurement. The 8-week time frame after surgery is ample to allow the PSA to clear, given a half-life of 2 to 3 days (Oesterling, 1991). The date of failure is the date of the first detectable PSA.

Front 3

What is the old ASTRO definition of relapse after radiation treatment?

Back 3

Biochemical failure after radiation therapy has been defined by the American Society for Therapeutic
Radiology and Oncology (ASTRO) as three consecutive PSA rises, optimally separated by 3 months
between measurements, after radiation therapy starting at least 2 years after the start of radiation, with the time of failure as the midpoint between the nadir and the first confirmed rise

Front 4

What are the problems with the ASTRO definition?

Back 4

Even ASTRO, however, has recognized that such a definition has its shortcomings. Because cell death that follows radiation therapy is a post-mitotic event, some radiation therapists suggest a minimum 18-month period of observation for nadir values to occur (Critz, 2002). In other cases, transient elevations in PSA level are documented that do not represent treatment failures. These so-called bounces have been reported in 12% to 61% of cases as long as 18 to 36 months after treatment (Taplin, 2003), and there are no validated guidelines to differentiate a bounce from recurrent disease.

Front 5

Why are radiographic studies not very helpful in the scenario of the rising PSA after local therapy?

Back 5

By definition, the finding of overt radiographic metastases on an imaging study signifies that a patient is in the state of clinical metastases, non-castrate disease, and no longer in the state of a rising PSA level.

Nevertheless, to ensure that patients do indeed have a rising PSA level in the absence of radiographic metastases, a staging evaluation should be undertaken. However, bone scintigraphy and computed tomography of the abdomen and pelvis, the traditional modalities used, are of limited value because they are insensitive at detecting early metastatic disease.

Front 6

What is the PSA level usually have to rise to before a bone scan will show up positive?

Back 6

In most series, PSA levels will be well above 20 to 30 ng/mL before bone scintigraphy reflects metastatic disease.

Front 7

What things can cause a false positive bone scan?

Back 7

Even when bone scintigraphy detects an abnormality, tracer uptake in areas of trauma, infection, or inflammation can easily be mistaken for metastatic disease.

Front 8

Why is a CT scan so crappy when looking at this patient population?

Back 8

An additional factor is that in many cases, soft tissue disease never develops even when advanced osseous disease is present. In an analysis of 134 men registered to contemporary clinical trials for
patients with castrate metastatic disease, only 15% of patients had exclusively soft tissue disease, and 45% had disease both in bone and in soft tissue. Only 50% of these patients had soft tissue lesions of sufficient size to be measurable, and the majority of these lesions were small lymph nodes on the order of 2.5 cm

Front 9

What if you could do a biopsy in the local prostate bed after local therapy and determine your treatment based on that, huh?

Back 9

However, most patients will not have palpable lesions, and most patients will not have evidence of locally recurrent disease. The yield of blind biopsies in the prostate bed is usually low, tends not to affect clinical decision-making, poorly predicts for the efficacy of salvage radiation therapy, and should not be considered a standard of care

Front 10

What about the same scenario in a patient after external beam radiation therapy?

Back 10

By contrast, biopsy proof of locally persistent disease in the prostate after external beam radiation therapy is essential before recommending that a patient receive a salvage radical prostatectomy, cryosurgery, brachytherapy, or intraprostatic biologic or cytotoxic treatment. The risk of false-positive biopsy findings declines after 2 years from the completion of radiation therapy.

Front 11

What are characteristics that predict a patient will have good results from salvage radiation after prostatectomy? In other words you think it is locally recurrent disease not systemic?

Back 11

The first question the clinician evaluating a patient with a rising PSA level must address is, Where is the disease? In general, low pretreatment PSA levels, lower grade tumors, low clinical or pathologic staging, late time from definitive local therapy to PSA relapse, and long PSA doubling times generally prognosticate a low likelihood for development of distant, radiographically apparent metastases. Such patients can have durable remissions after salvage radiation therapy to the prostate bed

Front 12

What are predictors of failure of salvage radiation after prostatectomy?

Back 12

predictors of progression after salvage radiation therapy were Gleason score of 8 to 10,preradiotherapy PSA level above 2.0 ng/ml, negative surgical margins, PSA doubling time of 10 months or less, and seminal vesicle invasion

Front 13

What are some predictors of metastatic disease?

Back 13

As one would anticipate, high-grade disease, short interval to biochemical relapse (2 years or less versus longer than 2 years), and PSA doubling time of less than 10 months versus 10 months or longer predicted for a shorter time to radiographic progression. In an updated analysis, time to PSA failure was no longer predictive when PSA doubling time was considered (Eisenberger et al, 2003). In numerous studies, PSA doubling time is the dominant factor used to assess the risk for development of metastasis-free survival In one study, a PSA doubling time of 6 months or less was associated with a 5-year progression-free survival of 64% versus 93% of patients who had a longer PSA doubling time

Front 14

How does ADT affect PSA doubling times in these patients?

Back 14

Another confounder in calculating PSA doubling time is the effect of neoadjuvant or adjuvant hormone therapy during radiation therapy. Rapid testosterone recovery may induce a rapid rise in PSA level, which may not reflect disease kinetics. Such a patient may not be at a significant risk for development of metastatic disease despite a seemingly rapid doubling time, because were he observed for a sufficient time for the testosterone level to stabilize, the rate of rise in PSA level may plateau or at least slow.

Front 15

What is the argument against early hormone therapy in the patient with rising PSA after local definitive treatment?

Back 15

Such practitioners argue that there are no clinical data to demonstrate that hormones applied at biochemical relapse make patients live longer than hormones applied at the time of metastatic disease and that early hormone therapy subjects such patients to a risk of impotence, gynecomastia, depression, weight gain, osteoporosis, fatigue, anemia, and other hormone-related disorders with no proven benefit.

Front 16

What percentage of men with newly diagnosed prostate cancer have locally advanced (T3 Nx/+ M0) disease?

Back 16

10%. However, later in the chapter, the book mentions a CaPSURE study from 2003 saying the presence of locally advanced disease decreased from 12% to 3.5% between 1990 and 2002.

Front 17

How well does TRUS accurately identify extraprostatic disease? Why is this?

Back 17

Studies vary, but more contemporary series suggest relatively poor reliability. In general, TRUS understages rather than overstages prostate cancer.
Interobserver variability, subtle signs of extraprostatic spread, and low volume tumors

Front 18

What survival rates can be expected after prostatectomy for clinical stage T3 tumors?

Back 18

In examining all reports, overall survival ranges from 64% to 96% at 5 years, 12.5% to 72% at 10 years, and 20% to 51% at 15 years. In more contemporary cohorts, cancer-specific survival rates are higher, with 85% to 92% and 79% to 82% at 5 and 10 years, respectively.

Front 19

For pathologic stage T3 tumors after prostatectomy, how does the presence of focal or established extracapsular extension change survival rates? What about SV invasion or positive nodes?

Back 19

The rate of clinical progression at 5 years increases from 7% for organ-confined disease to 18% for focal extracapsular extension and 35% for established extracapsular extension.
SV invasion increases progression at 5 years to 86%, and to 95% with nodes.

Front 20

Has neoadjuvant androgen deprivation been shown to downstage clinically, pathologically, or both? Overall, how can the benefit of neoadjuvant hormones be characterized?

Back 20

Consistently noted have been significant reductions in prostate volume, tumor volume, and PSA level, with maximal effects occurring during the first two months. Clinical downstaging occurs in 32%-90% of cases, however only 20% of such patients have organ-confined disease at the time of prostatectomy. Pathologic downstaging is significantly less common, ranging from 8% to 31%.
For locally advanced tumors (specifically, clinical T3 tumors), current data do not support a significant benefit.

Front 21

What’s the bottom line with adjuvant radiation? Which patients may see the most benefit?

Back 21

n select high risk patients, it improves local control and may reduce biochemical relapse, with a biochemical-free survival at 5 years ranging from 50-88% (compared to 30%-50% with surgery alone).
Albeit with limited data, men with SV invasion who achieve a low PSA nadir post prostatectomy may be a more favorable group. Conversely, men with a PSA that doesn’t have a low nadir post prostatectomy may harbor nodes or distant disease and be worse candidates for adjuvant RT.

Front 22

For which patient population does adjuvant androgen deprivation therapy show benefit?

Back 22

Recent publications provide some evidence supporting a benefit of early AD after radical prostatectomy in high-risk men with locoregional disease spread.
A study randomizing men with nodes after prostatectomy (cT1-T2) to adjuvant versus delayed AD found that at a median f/u of 7 years, adjuvant AD decreased recurrence (82% to 23%) and increased survival (65% to 85%).

Front 23

Summarize what was found in the Radiation Therapy Oncology Group (RTOC) trial examining the neoadjuvant combination of AD and RT. What is the general consensus?

Back 23

At 8 years, the PSA-free survival in the AD plus RT group was 24% compared to 10% for RT alone. No difference in overall survival between the groups was found.
Neoadjuvant and concurrent AD appears to be appropriate in high-risk patients undergoing RT.

Front 24

True or false. Studies have found that the benefits of adjuvant AD plus RT for locally advanced prostate cancer, both short and long term, outweigh the associated side effects in number-needed-to-treat analyses.

Back 24

True

Front 25

What are important pathologic criteria for predicting prognosis after radical prostatectomy?

Back 25

Gleason score, margin status, presence of non organ-confined disease

Front 26

What are Partin Tables?

Back 26

Preoperative predictions of pathologic stage for men undergoing radical prostatectomy for clinically localized disease

Front 27

What is the actuarial PSA-free survival after surgery in high-risk men at 5-7 years?

Back 27

50%