How Common Is Recurrence Of Prostate Cancer
According to the American Cancer Society, nearly 100% of men with low- to intermediate-grade prostate cancer can expect to live at least five years after the initial diagnosis. Since many men who get prostate cancer are already elderly, they are more likely to die from causes other than the cancer.
More than 90% of the time prostate cancer is discovered while it is either confined to the prostate gland or has spread beyond the prostate only to a small degree, referred to as regional spread.
Among the less than 10% of men whose prostate cancers have already spread to distant parts of the body at the time of diagnosis, about 30% are expected to survive at least five years.
Selection Of Hormonal Agents
Androgen deprivation therapy, either through chemical castration or, far more rarely, through orchiectomy, is one reasonable standard of care for BCR prostate cancer after maximal local therapy.24 Gonadotrophin-releasing hormone agonists, including leuprolide and goserelin, have been the primary medical castration therapies in the Western world. Recently, a GnRH antagonist, degarelix, has been gaining momentum in the first-line setting because clinical trial data suggest that it results in more rapid reduction of testosterone and marginally longer PSA progression-free survival intervals than leuprolide.25 In addition, patients on degarelix do not experience clinical flare and therefore do not require a short course of androgen receptor antagonists that are often prescribed for patients initiating leuprolide or goserelin. One potential disadvantage of degarelix is the requirement for monthly administration, since longer formulations of this compound do not exist at the present time. However, both GnRH agonists and antagonists remain reasonable options for initial hormonal treatment of patients with BCR prostate cancer.
Additional Treatment After Surgery
Additional treatment can come with one of two approaches: treatment given as adjuvant therapy , or as salvage therapy . In the modern era, most additional treatment is given as salvage therapy because firstly this spares unnecessary treatment for men who would never experience recurrence, and secondly because the success rates of the two approaches appear to be the same.
Regardless of whether an adjuvant or salvage therapy approach is taken, the main treatment options following biochemical recurrence are:
- Radiotherapy this is the commonest approach. Because scans dont show metastatic deposits until the PSA is more than 0.5 ng/ml and because radiotherapy is more effective when given before this level is reached, the radiotherapy energy is delivered to the prostate bed. This is because we know that this is the commonest site of recurrence in most men, and that 80% of men treated in this way will be cured.
- Active surveillance this is appropriate for a very slowly-rising PSA in an elderly patient who has no symptoms.
- Hormonal therapy in many ways this is the least appealing option as it causes symptoms but does not cure anyone, although it does control the recurrence and lower the PSA.
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Suo 202: Theranostics In High
At the Annual Meeting of the Society of Urologic Oncology , there was a session focused on prostate specific membrane antigen and prostate cancer. In the context of this session, Dr. Karen Elizabeth Hoffman presented the evolving role of theranostics in high-risk localized prostate cancer.
Dr. Hoffman began by emphasizing that standard treatments including radical prostatectomy or radiotherapy with androgen deprivation therapy are not sufficient for a subset of patients with localized high risk disease. Accordingly, biochemical recurrence rates range from 20% up to 50% of these patients by five-years after treatment, with varying rates according to oncologic risk. While biochemical recurrence represents an important clinical endpoint, even more importantly, she emphasized that these patients are at substantial risk of metastatic progression. Across a number of trials assessing external beam radiotherapy with ADT, she emphasized that 5-year metastasis free survival is approximately 85%, with some variation according to patient cohorts and treatment paradigms.
To that end, Dr. Hoffman discussed the potential for theranostic radiation delivery to address micrometastatic disease in patients with high-risk prostate cancer, with obviously open and unanswered questions regarding the integration with current treatment paradigms including radical prostatectomy and radiotherapy.
The Frequency Of Bcr Cp Crd And Rates Of Bpfs Cpfs Css
Median time of follow-up after RP was 64 months. Over this time, 207 men experienced BCR. One hundred twenty-seven men had BCR in the following year after RP, 27 in the second year, 16 in the third, 14 in the fourth, 7 in the fifth, and 16 patients had BCR after 5 years . Of 207 men, 181 received salvage radiotherapy or hormone therapy or both sRT + HT due to BCR.
Figure 1. Risk of biochemical recurrence by the following year after radical prostatectomy .
CP was diagnosed in 49 cases. Median time from BCR to CP was 17 months. Twelve men had metastases in lymph nodes, 11 had metastases in bones, 19 had metastases in lymph nodes and bones, 1 had visceral metastases, and 6 had local recurrence in the surgical bed. During the follow-up, 72 patients died. In 24 cases PCa was the cause of death.
According to the DAmico risk classification, the 5-year BPFS rate after RP of patients with one risk factor was 57.7%, and that with two factors was 34.4%. All patients with three risk factors had BCR in the first 5 years after RP .
In all study cohorts, 5- and 10-year BPFS rate was 49.2 and 34.2%, respectively. CPFS rate was 89.2 and 81% and CSS rate was 95.6 and 90.1%, respectively.
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Why Does Breast Cancer Come Back After Treatment
Even with the best treatment, cancer can come back. If just a few cancer cells remain in your body after your initial treatment, those cells can spread through the blood or lymph system and grow. This may happen from a few months to many years after the first diagnosis.
If your breast cancer has come back, you may second-guess your previous treatment choices. But the fact is, there is no guarantee with any treatment. Now it is time to make new decisions and explore other treatment options.
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What Factors Determine The Likelihood Of Recurrence
Several signs can point to a prostate cancer that has come back or spread, including:
- Lymph node involvement. Men who have cancer cells in the lymph nodes in the pelvic region may be more likely to have a recurrence.
- Tumor size. In general, the larger the tumor, the greater the chance of recurrence.
- Gleason score. The higher the grade, the greater the chance of recurrence. Your doctor can tell you your score when the biopsy results come back from the laboratory.
- Stage. The stage of a cancer is one of the most important factors for selecting treatment options, as well as for predicting future outlook of the cancer.
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Assessing Metastases And Local Recurrence
Once BCR has been detected, it is important to try to establish whether this represents local recurrence or disseminated disease, or both, in order to guide subsequent treatment decisions. Importantly, metastatic disease must be acceptably ruled out before subjecting patients to local salvage treatment, owing to the significant morbidity associated with such treatments. Regardless of whether BCR is detected post-RP or post-RT, the same principles of imaging apply.
Experimental Approaches For Psa
The current treatment landscape for prostate cancer patients experiencing biochemical recurrence offers no ideal systemic approach. Benefits of early initiation of continuous ADT or intermittent ADT are offset by the risk of osteopenia and cardiovascular disease, in addition to the bothersome and common side effects, including hot flashes and erectile dysfunction. Patients with slower PSADT, for whom ADT may not be immediately indicated, face years of anxiety and often seek treatments that delay PSA progression and development of metastases. To this end, researchers are investigating 3 approaches to complement or replace those described earlier in this review for the management of BCR patients: 1) the use of novel agents or vaccination approaches to enhance and/or supplement ADT 2) the use of pharmaceutical agents or combinations of agents that may already be approved by the US FDA for treatment of other diseases and have demonstrated preclinical activity against hormone-sensitive prostate cancer and 3) the use of natural products that have shown preclinical activity against hormone-sensitive prostate cancer. Table 1 shows a selected list of completed or ongoing clinical trials investigating a number of such therapeutic strategies in patients with BCR, nonmetastatic prostate cancer.
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Diagnostic Evaluation After Psa Recurrence
No formal guidelines have been published defining the frequency of diagnostic evaluations for patients following BCR who choose to undergo surveillance rather than initiating early hormonal therapy. In the authorsâ opinion, it is reasonable to monitor serum PSA every 3 months and to perform annual technetium-99 bone scans and bi-annual computed tomography scans in patients at high risk of metastatic progression as determined by PSA levels and/or a rapid PSADT of 9 months or less. In one retrospective study describing the natural history of untreated PSA-recurrent prostate cancer after prostatectomy, it was observed that men with a PSADT of 9 months or less had a median metastasis-free survival of 2 years after biochemical recurrence.8 Another analysis from this same population reported that the median PSA value at the time of first radiographic metastasis was 31.4 ng/mL .20 These figures may help to determine whether a particular patient might be at a more imminent risk of metastasis, allowing for more frequent PSA evaluations or imaging tests to be obtained at the treating physicianâs discretion.
Justification For A New Guideline
Clinicians treating men with advanced prostate cancer are challenged with the rapidly evolving prostate cancer landscape given the approval of new classes of agents for use in various prostate cancer disease states. The increasing complexity of advanced prostate cancer management underscores the need for the current clinical practice guideline, developed to provide a rational basis for treatment of patients with advanced disease, based on currently available published data. To assist in clinical decision-making, guideline recommendations are furnished according to disease state across the entire continuum of advanced prostate cancer.
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Psa Bounce Vs Biochemical Recurrence After Prostate Cancer Sbrt Probed
Investigators have identified factors that could be useful in managing patients who experience rising PSA levels following stereotactic body radiation therapy for prostate cancer, according to a presentation at the American Urological Associations 2022 annual meeting.
These factors the timing at which a PSA rise occurs, PSA nadir value, and time to PSA nadir could help distinguish PSA bounce from biochemical recurrence of disease.
Ashley Monaco, BS, of the New York Institute of Technology College of Osteopathic Medicine in Glen Head, New York, and colleagues studied 170 men who underwent primary SBRT. The men had a median age of 72 years and an average follow-up duration of 75 months. Of these, 28 experienced PSA bounce and 42 had BCR.
Compared with patients who did not experience PSA bounce or BCR, those with PSA bounce were younger, had significantly lower PSA doubling time, and took significantly longer to reach PSA nadir. Compared with the BCR group, men with PSA bounce had a lower final PSA nadir and took longer to reach final PSA nadir . PSA bounce occurred significantly earlier than BCR .
The study excluded patients with less than 18 months of follow-up or who were missing more than 3 PSA measurements following SBRT. The investigators defined PSA bounce as a rise of greater than 0.2 ng/mL over the pre-rise nadir followed by a decline without intervention. They defined BCR according to Phoenix criteria .
Reference
Searches And Article Selection
A research librarian conducted searches in Ovid MEDLINE , Cochrane Central Register of Controlled Trials , and Cochrane Database of Systematic Reviews . An updated search was conducted prior to publication through January 20, 2020. The methodology team supplemented searches of electronic databases with the studies included in the prior AUA review and by reviewing reference lists of relevant articles.
The methodology team developed criteria for inclusion and exclusion of studies based on the Key Questions and the populations, interventions, comparators, outcomes, and settings of interest. The population was patients with advanced prostate cancer as described in Table 3. Treatments included first and second line antiandrogens, immunotherapy, chemotherapy, radiation therapy, surgery, radiopharmaceuticals, and surveillance strategies. Comparisons were against placebo, no therapy, or another active intervention and intermittent versus continuous therapy. Outcomes included overall survival , prostate cancer mortality, progression-free survival , prostate-specific antigen progression-free survival , failure-free survival, metastases-free survival, time to metastases, time to progression, skeletal events, and adverse events.
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Differences Among Risk Groups
Men with PCa have been classified into low-, intermediate- and high-risk Groups for tumor recurrence and disease specific mortality, based on PSA level, clinical or pathological staging and GS. High-risk patients have PSA level 20ng/mL or GS 8 or clinical/pathological stage T2c . Lymph-node positive and PSM have also been reported as poor prognosis factors.
Risk Group classification predicts biochemical and clinical progression as well as PCa specific mortality and overall survival. The risk of disease progression in these groups has been validated for patients submited to RP in many studies. In patients from Mayo Clinic, BCR rates were 2.3 and 3.3-fold greater in high and intermediate-risk in comparison with low-risk patients, respectively. In those patients, mortality rates in high and intermediate-risk patients were greater than 11 and 6-fold over low-risk men .
Therefore, it is crutial to understand the role of each clinical and pathologic feature in PCa BCR and disease progression.
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Timing And Duration Of Adt
Physicians wishing to treat BCR prostate cancer patients with ADT face 2 key timing questions: 1) whether to initiate ADT immediately upon PSA recurrence or to defer its use until after clinical/radiographic progression occurs, and 2) whether to use continuous administration of ADT or intermittent cyclic administration of ADT. As of December 2012, the American Society of Clinical Oncology had not provided definitive guidelines addressing either of these questions. We will review the relevant clinical trial data that may guide clinicians with respect to these 2 issues.
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Salvage Radiation For Psa
Three large retrospective studies provide evidence that early salvage radiation therapy, delivered to patients with rapid PSADT, or while the PSA levels remain below 2.0 ng/mL, impacts survival of prostate cancer patients with BCR. A study at Duke University examined 519 patients who experienced BCR after prostatectomy, of which 219 patients received salvage radiation therapy. That study stratified the patients by PSADT . Salvage radiation therapy significantly improved overall survival in both groups at a median follow-up of 11.3 years, with all-cause mortality hazard ratios for death of 0.53 and 0.52 for those with faster and slower PSADT, respectively.
Although another large retrospective trial has not shown overall survival benefits from salvage radiation treatment after prostatectomy, the 2 studies described above provide adequate evidence that salvage radiation therapy may positively alter the progression of the disease when administered within 2 years of BCR and while the absolute PSA remains below 2 ng/mL . The finding of improved prostate cancerâspecific survival in men with PSADT less than 6 months is provocative , and should be confirmed by additional studies.
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Predicting Whose Cancer Might Recur
Much of this research takes place at the FASTMAN Movember Centre of Excellence, which we launched in 2014 in partnership with Movember.
This centre shared between Belfast and Manchester is a research hub. It brings together world-leading scientists and clinicians with different areas of expertise to tackle big questions in prostate cancer research from fresh perspectives.
With these diverse, world-class teams, FASTMAN aims to accelerate prostate cancer research so it can benefit men as quickly as possible.
In particular, these researchers are looking for new ways to find out which men are more likely to develop recurrent disease before they start their initial treatment.
Then, by improving and refining radiotherapy treatments, they hope to reduce and prevent recurrence altogether.
For example, Dr Chris Armstrong at Queens University Belfast has been developing new drugs that could help certain men respond better to radiotherapy. These men have a mutation in a gene that is meant to stop cancer cells growing out of control making it more likely that their cancer will come back after radiotherapy. Dr Armstrong hopes that giving the new drug alongside radiotherapy will reduce these mens risk of recurrent prostate cancer.
Meanwhile, in the Belfast arm, Queens University Belfast has just been awarded nearly £2m in further funding for its prostate cancer research, showing that our joint investment in the centre is bringing in further funds to supercharge research there.
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Research Needs And Future Directions
Ongoing Clinical Trials. Several ongoing clinical trials will help to clarify the magnitude and impact of ART or SRT, the relative value of combining RT with hormone and other therapies, and potentially make clear which patients are more likely to benefit from specific therapies, therapy combinations, and therapeutic contexts.
RTOG 0534 is randomizing post-prostatectomy patients with Gleason scores 9, with or without positive margins, and with post-RP PSA of 0.1 ng/mL to < 2.0 ng/mL to prostate bed RT, prostate bed RT plus short-term ADT or pelvic lymph node RT plus prostate bed RT plus short-term ADT. Patients are stratified by SVI status, Gleason score 7 or 8-9, pre-RT PSA of 0.1 to 1.0 ng/mL or > 1.0 to
The RAVES trial was a phase III multi-center trial taking place in Australia and New Zealand comparing ART with early SRT in patients with positive margins or EPE. The primary trial aim was to determine whether surveillance with early SRT results in equivalent biochemical control and improved QoL when compared with ART. Secondary outcomes include QoL, toxicity, anxiety/depression, bRFS, OS, CSS, time to distant failure, time to local failure, time to initiation of hormone therapy, quality adjusted life years, and cost-utility. The rate of participant accrual diminished over time, and the trial closed prematurely with entry of 333 of the 470 patients planned.
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