In the majority of prostate cancer cases currently diagnosed, the disease is localized, with only approximately 7% of patients with metastatic disease.
Localized disease is classified, according to a risk of progression or death on the basis of tumor stage, PSA level, and tumor grade.
In a patient with an elevated PSA level the use of multiparametric Magnetic resonance imaging is used to selectively biopsy only patients with a score of 3 to 5 on the PIRADS, which classifies a lesion on a scale of 1-5 with higher scores, indicating a higher suspicion of cancer.
Additional risk stratification methods beyond clinical stage, PSA level, and Gleason score are readily available and include genomic classifiers, which can provide prognostic information and help guide treatment.
tumor grade has traditionally been evaluated by the Gleason score, but recently grade groups, which ranges from group 1 to 5.
grade group 1 Gleason score 5-6
grade group 5 Gleason score 9 or 10.
A Gleason score of six is the lowest grade of prostate cancer.
In persons with localized disease, clinically significant prostate cancer is usually defined as grade group 2 or higher.
For localized disease, 10 year prostate cancer specific survival is approximately 95%: in contrast five-year survival is approximately 35% for metastatic disease.
Prostate specific membrane, antigen (PSMA) PET scans can better assist staging in patients with unfavorable intermediate or higher risk localized disease.
Localized Prostate Cancer: ProtecT Results
Men newly diagnosed with localized prostate cancer can rest assured that whatever their initial choice of therapy — whether surgery, radiation, or active monitoring — all will have a high probability for good long-term outcomes.
Prostate Testing for Cancer and Treatment (ProtecT) trial, in which more than 82,000 men were screened with prostate specific antigen (PSA) testing from 1999 through 2009.
Among these screened men, 2664 were diagnosed with localized prostate cancer, and 1643 men in this group were then randomly assigned to receive either radical prostatectomy, radiotherapy, or active monitoring.
At a median 15 years of follow-up there were no significant differences among the treatment groups in either prostate cancer death or all-cause mortality rates.
Prostatectomy or radiotherapy reduced the incidence of metastasis, local progression, and long-term androgen-deprivation therapy by half as compared with active monitoring; these reductions did not translate into differences in mortality at 15 years.
The vast majority of the trial patients were at low risk of favorable, intermediate risk, and today would be considered appropriate candidates for active surveillance.
The unfavorable intermediate risk or a high risk patients represented in under powered sub group.
Given the similarities in long-term survival outcomes regardless of the treatment assigned at baseline, the choice of therapy involves weighing trade-offs between benefits and harms associated with treatments for localized prostate cancer.
The adverse effects of radiotherapy and surgery on sexual and urinary function persisted for up to 12 years.
In the active monitoring group, an increase of at least 50% in the PSA level over 1 year would then trigger a review, with the patient then either continuing on monitoring or going on to further testing and either radiotherapy, radical prostatectomy, or palliative care.
Active monitoring as performed in the ProtecT trial is not be used today: serial multiparametric MRI assessments.
The increased rate of metastasis that was noted in the active monitoring group would likely be diminished with the active surveillance protocols that are being used today.
The study enrolled 1643 men diagnosed with localized prostate cancer and with a life expectancy of more than 10 years, randomly assigning them to receive either active monitoring (545 patients), radical prostatectomy (553), or external-beam radiotherapy (545).
Patients assigned to radiotherapy also received neoadjuvant androgen-deprivation therapy (ADT) for 3 to 6 months, and patients assigned to surgery who had positive surgical
margins, extracapsular disease, or a residual postoperative PSA of 0.2 ng/mL or higher were offered the option of adjuvant or salvage radiotherapy.
Follow-up was complete for 1610 (98%) of all patients enrolled and randomized.
In all, 45 men died from prostate cancer. The rates of prostate cancer deaths by treatment type were 3.1% with active monitoring, 2.2% with prostatectomy, and 2.9% with radiotherapy (P = .53).
Rates of death from any cause were 16.2, 15.0, and 15.0 per 1000 person-years, respectively, and did not differ significantly between the treatment groups.
Significantly more metastases occurred among men who were assigned to active monitoring, at 9.4% compared with 4.7% assigned to prostatectomy (hazard ratio (HR), 0.47) and 5% assigned to radiation (HR, 0.48).
More men assigned to active monitoring started on long-term ADT (12.7%) compared with 7.2% assigned to prostatectomy and 7.7% assigned to radiation.
The hazard ratio for ADT use compared with active monitoring was 0.54 in both the surgery and radiation groups, and these differences were statistically significant.
Significantly more men on active monitoring had clinical progression, initiation of long-term ADT, diagnosis of clinical T3 or T4 disease, ureteric obstruction, rectal fistula, or urinary catheterization because of tumor growth than men treated with surgery or radiation.
These significant differences in disease progression in the group on active monitoring compared with the other two groups who had either surgery or radiotherapy did not translate to differences in overall survival.
Results: men with newly diagnosed, localized prostate cancer and their clinicians can take the time to carefully consider the trade-offs between harms and benefits of treatments when making management decisions.
Among patients treated for localized prostate cancer radical prostatectomy, is associated with worse urinary incontinence, but not sexual function at 10 year, follow up as compared with radiotherapy, or surveillance some of people with more favorable, prognosis, and compared with radiotherapy for those with unfavorable prognosis.
Among men with unfavorable prognosis disease, external beam radiotherapy with androgen deprivation therapy was associated with worse bowel and hormone function that 10 year follow up compared with radical prostatectomy (Barocas DA).