Treatment of localized prostate cancer by approximately one third of 230,000 newly diagnosed patients each year.
Gold standard for surgery of localized prostate cancer.
Radical prostatectomy can be applied in patients with localized prostate cancer and a life expectancy of more than 10 years.
Prostate cancer-specific survival is approximately 93-95% after radical prostatectomy (Bill-Axelson A et al).
Approximately 2/3 of patients are cured of prostate cancer, but 1/3 will have recurrent disease within 10 years.
Following radical prostatectomy serum PSA is expected to be undetectable, or at the lowest level of detection by 4 weeks postoperatively.
Unlikely to benefit patients whose life expectancy is less than 10 years.
Generally not offered treatment older than 75 years, as a result of high perioperative mortality risk
Biochemical relapse in patients with organ defined disease after radical prostatectomy by PSA of 0.2 ng/ml or greater, followed by a confirmatory test with the same result.
Some patients have a low measurable PSA after radical prostatectomy which persists and does not reflect recurrent cancer.
Retropubic approach via an infraumbilical incision has become the most common open surgical approach.
Extraprostatic disease detected at the time of surgery for prostate cancer in 38-52% of patients.
Approximately one third of patients will have a positive margin, another 9% will have seminal vesicle invasion, and about one third will have extracapsular extension.
The PSA should become undetectable within 6 weeks of radical prostatectomy.
The initial postoperative PSA is measured 6-12 weeks after radiacal prostatectomy.
In a retrospective study of 358 pateints undergoing a radiacal prostatectomy it was found that when the PSA rose to greater than 0.2 ng/mL after surgery the 1 and 3 year risk of additional PSA progression were 86% and 100, respectively (Freedland SJ).
The half-life of PSA is around 3 days (Stamey TA).
Additional adjuvant radiation in high risk patients, as above, have significant benefits for pT3 disease (Bolla, M, Thompson,I).
Extraprostatic disease at surgery including extension beyond the prostate, positive surgical margins, invasion of the seminal vesicles associated with recurrence, progressive disease and death.
In a retrospective analysis of radical prostatectomy of 712 patients European database with a baseline PSA level > 20 ng/ml: Group A: Patients with a preoperative PSA level >100 ng/ml, Group B: Patients with a preoperative PSA level between 50.1 and 100 ng/ml , Group C: Patients with a preoperative PSA level between 20.1 and 50 ng/ml-10-year projected prostate cancer-specific survival appeared to be significantly affected by the baseline PSA level with 79.8 percent in Group A, 85.4 percent in Group B, 90.9 percent in Group C, 10-year projected overall survival was apparently not significantly affected by the baseline PSA level, 59.6 percent in Group A, 71.8 percent in Group B,75.3 percent in Group C, and at a median follow-up of 78.7 months, rates of biochemical progression-free survival were, 6.6 percent in Group A, 8.3 percent in Group B, 25.8 percent in Group C. (Gontero et al).
In patients with high risk Gleason score of eight or greater at biopsy, there is suboptimal PSA control at five years following prostatectomy, and in the setting of uninvolved seminal vesicles or lymph nodes, the dominant pattern of failure is local, and therefore postoperative radiotherapy should be considered.
Postoperative radiation should be considered following radical prostatectomy with surgical margin involvement, extraprostatic extension, and or seminal vesicle invasion is present.
In the above study the authors conclude that 10-year prostate cancer-specific survival is high — even among men with baseline PSA levels >100 ng/ml, and that radical prostatectomy may be an appropriate treatment option even for some men whose baseline PSA level is >100 ng/ml.
Studies comparing all cause and cancer specific mortality of radical prostatectomy versus observation for the management of localized cancer of the prostate shows radical prostatectomy does not significantly reduce overall mortality compared with observation at 10 years of follow-up.
In the Scandinavian Prostate Cancer Group Study-4 reduced prostate cancer mortality compared to the surveillance, but not patients older than 65 years of age.
In a follow up study of the above trial up to 29 years after the start of the study, and point at which 80% of the men enrolled had died: The men had clinically detected localized prostate cancer and a long life expectancy.
In the above study radical prostatectomy, resulted in a mean of 2.9 years of life gained, and it was noted that a high Gleason score and the presence of extracapsular extension in the prostatectomy specimens were highly predictive of death from prostate cancer.
Robotic tools such as the da Vinci system allow for surgery with minimal surgical incisions and greater precision, with increased cost over open surgery or laparoscopic approach.
Optimal management in patients with extraprostatic cancer is presently unknown.
Complications include urinary incontinence, weakness, and impotence.
Risk of complications 27%, compared to 22% for laparoscopic prostatectomy.
Incontinence 0.5-30% of patients.
Radical type associated with a mortality of 0.1-0.7%.
Associated with erectile dysfunction from 16-82% of cases.
As many as 65% of men continue to experience incontinence up to five years after surgery (Penson DF et al).
Post prostatectomy incontinence attributed to intrinsic sphincter deficiency and/or detrusor dysfunction, leading to stress and/or urgenct incontinence, respectively.
Surgical intervention for incontinence is effective in post prostatectomy incontinence.
Perioperative pelvic floor muscle training can significantly reduce the duration and severity of incontinence in the early post-prostatectomy period.
A randomized controlled trial demonstrated that behavioral therapy with pelvic floor muscle exercises, to prevent stress and urge incontinence is an effective treatment for post-prostatectomy incontinence that persists even years after surgery (Goode PS et al).
At the end of 1 year 2-4% of patients with disease confined to the prostate will require a pad for stress incontinence, while 6-8% of those requiring a wide surgical resection will have this problem.
The nerves innervating the penile corpus cavernosum, allowing for erectile function, travel along the posterior-lateral aspect of the prostate, outside of the prostate fascia, but within the visceral layer of overlying levator fascia.
Risk of impotence depends on age and potency.
If both neurovascular bundles are spared in an individual less than 60 years of age and who presented with good preoperative erectile function there is a 70-80% chance of recovering erectile function within 1 year or more after surgery, and the remainder of such patients (20-30% of cases) will need phosphodiesterase inhibitors for recovery, with variable results.
If one neurovascular bundle is removed there is a 50% probability of maintaining potency, while the probability decreases the 10-15% if both bundles are removed.
In a randomized study of 731 men with localized PC, mean age 67 years, PSA 7.8 ng to radical prostatectomy or observation: radical prostatectomy did not significantly reduce all-cause or PC mortality through 12 years of follow-up (Prostate Cancer Intervention versus Observation Trial (PIVOT).
In the Scandinavian prostate cancer group study number for the randomized trial of radical prostatectomy versus watchful waiting in men with localized prostate cancer, diagnosed before PSA testing showed a survival benefit of radical prostatectomy is compared with observation at 15 years.
Am update of the above study with 23.2 years of follow-up confirmed a substantial reduction in mortality after radical prostatectomy versus watchful waiting.
Radical prostatectomy by open retropubic technique allows the surgeon to enter the retroperitoneal space and obviates the need to enter the peritoneal cavity.
Open technique radical prostatectomy takes less time and is less expensive then robotic assisted laparoscopic prostatectomy.
With robotic assisted laparoscopic prostatectomy the surgeon enters two cavities, the peritoneal cavity and the retroperitoneum.
Radical Prostatectomy as Primary Treatment for Prostate Cancer Leads to Better Survival
Of men who received prior RT or surgery for localized prostate cancer, those that had RT were found to have a 32% higher risk of developing castrate-resistant disease.
Compared with local radiation therapy (RT), radical prostatectomy (RP) as primary treatment for prostate cancer may result in a lower risk of castrate-resistant disease and superior overall survival (OS) from the time of metastasis (Shahait M).
After developing metastatic disease, mortality was significantly higher among the men who received RT alone versus those who underwent RP
The study was only patients who received local treatment and progressed to metastases.
The RP group was younger, had a lower prostate-specific antigen (PSA) level at prostate cancer diagnosis (7.8 vs 10.9 were more likely to have a Gleason score of 8 or higher.
The group treated with RT was more likely to receive androgen deprivation therapy (ADT) before metastasis compared with the RP group.
The unadjusted hazard ratio for castrate-resistant disease in the group who received RT was 1.45.
Men who received RT alone had 77% higher overall mortality after developing metastatic disease compared with men who underwent RP.
A growing body of evidence that supports the benefit of extirpation of the primary disease on OS after developing metastatic disease.
It is proposed use of ADT as well as RT may potentiate epithelial-mesenchymal transition, which mediates tumor invasion, metastasis, and the development of castrate resistance, leading to worse outcomes.
Radical prostatectomy may cure more than half of men considered to have high-risk tumors, but biochemical recurrence is possible in about 30% of patients with adverse features.
Surgery is often followed by adjuvant radiotherapy to the prostate bed.
Alternatively, patients may be observed after surgery, with radiotherapy only given once their prostate-specific antigen (PSA) levels start to rise.
Salvage radiotherapy avoids unnecessary treatment of those cured by surgery alone.
Three phase III randomized trials and a meta-analysis of the three trials showed that adjuvant radiotherapy did not have any benefit compared with salvage radiotherapy in men with early, high-risk prostate cancer.
Observation, with salvage radiotherapy for biochemical progression, should be the current standard of care for most patients with prostate cancer.
Earlier studies showing that adjuvant radiotherapy was associated with a decreased risk of recurrence in at-risk patients were confounded by either late use of salvage radiotherapy or no use of post-radical prostatectomy PSA monitoring or both.
Consensus regarding the optimal timing of radiotherapy after prostatectomy remains unmet.
A 2018 survey of 88 radiation oncologists found that 55% recommended adjuvant radiotherapy and 45% recommended salvage radiotherapy in the event of a recurrence.
RADICALS-RT trial included 1,396 patients with localized prostate cancer with a mean age 65, median PSA at diagnosis 7.9 ng/mL and associated with at least one high-risk characteristic pathologic T-stage 3 or 4, Gleason score 7-10, positive surgical margins, or preoperative PSA ≥10 ng/mL.
All patients underwent radical prostatectomy and were randomized to early adjuvant radiotherapy or to a watch-and-wait strategy of salvage irradiation. In the adjuvant group, radiation therapy was delivered within 6 months in 93% of patients, whereas a third of patients in the salvage group received radiotherapy within 8 years of surgery.
The 5-year biochemical progression-free survival (PFS) rate was 85% for patients in the adjuvant radiotherapy group and 88% for those in the salvage radiotherapy group.
This would mean that most men might avoid 20 or more trips to the hospital for radiotherapy and the accompanying costs and side effects of additional treatments. Ideally, they could be monitored, with radiotherapy given only when the cancer recurs.
The RAVES trial, and the GETUG-AFU 17 trial, as well as a meta-analysis all concluded similar results
The trials had demonstrated noninferiority of salvage radiotherapy, defined as a 5-year biochemical PFS rate within 10% of the rate for adjuvant radiotherapy.
The results of one study showed a 5-year biochemical PFS rate of 86% with adjuvant radiotherapy versus 87% with salvage radiotherapy.
Patients allocated to adjuvant radiation therapy had a higher incidence of grade ≥2 genitourinary toxicity.
Data support the use of salvage radiotherapy, as it results in similar biochemical control to adjuvant radiotherapy, spares around half of men from pelvic radiation, and is associated with significantly lower genitourinary toxicity.
The GETUG-AFU 17 randomized trial included 424 patients: After a median follow-up of 75 months, the adjuvant group had a 5-year EFS rate of 92% versus 90% for the patients allocated to delayed radiation therapy.
Meta-analysis of the three trials showed no evidence that event-free survival was improved with adjuvant radiotherapy compared with early salvage radiotherapy.
Three trials and a meta-analysis of trials failed to show a significant effect of adjuvant radiotherapy on biochemical progression or combined clinical events after radical prostatectomy for early, high-risk prostate cancer.
In the largest of the three trials, salvage radiotherapy was associated with a 3% absolute advantage for biochemical progression free, at 5 years, not reaching statistical significance.
The meta-analysis yielded a 5-year EFS rate of 89% with adjuvant radiotherapy and 88% with salvage therapy, also not significant.
The studies support the use of early salvage as opposed to adjuvant radiotherapy for many patients after radical prostatectomy, with the possible exception of those at high risk for progression, which comprises less than 20% of men in the three randomized trials, and for whom shared patient and clinician decision making should be considered.