Editing Biochemical Recurrence (section)

==== Options (6)§: ====
# '''Active surveillance/observation'''
# '''Local salvage therapy'''
## '''Salvage radical prostatectomy'''
##* '''In highly selected cases by highly experience surgeons (see below)'''
## '''Salvage cryosurgery'''
## '''Salvage brachytherapy'''
## '''Salvage high intensity focused ultrasound'''
# '''ADT (intermittent or continuous)'''
#*

===== Active surveillance/observation =====
* A reasonable option, particularly for lower risk patients with:
*# BCR >3 years from RT
*# PSADT ≥16 months
*# Pre-RT biopsy pathology grade group 1
** These features indicate a low liklihood of prostate cancer-specific mortality over a 10-year period
* Minimizes morbidity and is well suited for older patients and those who do not wish to undergo further treatments.
* '''May be considered in men with a life expectancy <10 years.'''

===== Local salvage therapy =====
* '''May potentially increase metastasis-free survival, delay initiation of ADT and eradicate recurrent/ residual disease in appropriately selected patients'''
** '''Unknown survival benefit'''
*** '''Studies comparing local salvage therapy vs. observation (and delayed intervention for metastasis) are lacking'''
* '''Biopsy-proven evidence of local recurrence should be obtained prior to local salvage therapy, given the potential for risk of complications with salvage therapy, particularly salvage radical prostatectomy'''
* '''Indications'''
** '''Biochemical recurrence after radiation therapy with'''
**# '''Clinically localized T1c-T2 disease'''
**# '''PSA <10.0 ng/ml at biochemical recurrence'''
**# '''No evidence of metastasis on prior evaluation'''
* '''Options (4):'''
*# '''Salvage radical prostatectomy'''
*# '''Salvage cryosurgery'''
*# '''Salvage brachytherapy'''
*# '''Salvage high intensity focused ultrasound'''

====== Salvage Radical Prostatectomy ======
* '''Historical'''
** '''Feasability first published in 1980 in a series of 18 patients from the Mayo Clinic. Reasons for SRP included the discovery of an enlarging indurated prostatic mass after radiotherapy and compliance with a radiation-surgery protocol that was initiated for a time in 1969. There were 0 deaths, 1 pulmonary emobolus, 0 patients complained of total urinary incontinence, and no rectal injury reported.§'''
* '''Utilization'''
** '''Not commonly used to treat biochemical recurrence after radical prostatectomy'''
** '''Technically challenging operation with the potential for serious complications'''
*** '''Should only be performed by experienced surgeons.'''
**** '''No published report on learning curve with SRP'''
* '''Indications'''
** '''NCCN§'''
*** '''Option for highly selected patients with local recurrence after EBRT, brachytherapy, or cryotherapy in the absence of metastases'''
** '''EAU§'''
*** '''Should be considered only in patients with (6):'''
***# '''Low co-morbidity'''
***# '''Life expectancy > 10 years'''
***# '''Initial clinical staging was T1 or T2'''
***# '''Initial biopsy ISUP grade < 2/3'''
***# '''Pre-salvage radical prostatectomy PSA < 10 ng/mL'''
***# '''No LN involvement or evidence of distant metastatic disease pre-salvage radical prostatectomy'''
** '''In summary, candidates for salvage surgery should be unrecognizable from the candidates we would choose for initial therapy with RRP and be highly motivated individuals who understand and accept the potentially higher morbidity associated with salvage surgery.'''
* '''Outcomes§§'''
** '''Oncologic'''
*** '''Improved oncologic outcomes observed over time may be due to improved patient selection and stage migration'''
*** '''Systematic reviews'''
**** '''Positive surgical margin rate: ≈20%'''
**** '''Median follow-up ranges from 4.6 to 120 mo'''
***** '''Wide range of follow-up partly explains wide ranges of survival'''
****** '''Longer follow-up periods show a non-statistically significant trend toward adiminished BCR-free survival'''
**** '''Biochemical recurrence-free survival'''
***** '''5 years: 47-82%'''
***** '''10 years: 28-53%'''
**** '''Cancer-specific survival'''
***** '''5 years: 89-100%'''
***** '''10 years: 70-83%'''
**** '''Overall survival'''
***** '''10 years: 54-90%'''
**** '''Prognostic factors§'''
****# '''Pre-SRP PSA'''
****# '''Considered the strongest prognostic factor; shown to significantly associated with PFS, CSS, and OS'''
****# '''Gleason score on post irridation prostate biopsy'''
****# '''Salvage RP Gleason score'''
****# '''Salvage RP pathologic stage'''
****# '''Salvage RP DNA ploidy'''
** '''Complications'''
*** '''Significant high perioperative morbidity'''
**** '''Relatively poor postoperative urinary and sexual health related functional outcomes compared to primary radical prostatetomy'''
*** '''Urinary incontinence'''
**** '''Radiotherapy causes fibrosis of the bladder neck and external sphincteric tissues, resulting in delayed healing of the vesico-urethral anastomosis (prolonged urinary extravasation), an increased incidence of bladder neck contracture and worse post-operative continence rate.'''
***** '''High rate of urinary incontinence is likely the greatest factor discouraging physicians from considering patients with radio recurrent prostate cancer for salvage RP.'''
***** '''Bladder neck contracture rate: 0-55%'''
****** '''A method that involves closing the opening in the bladder neck in 2 layers after prostate removal and making a new 26Fr to 30Fr opening made anterior, away from the radiation field has been described§'''
*** '''Erectile dysfunction'''
**** '''Extremely high incidence of erectile dysfunction before SRP'''
**** '''Post-SRP erectile function dropped significantly'''
***** '''Erectile function sufficient for sexual intercourse: 0-20%'''
*** '''Rectal injury'''
**** '''Definitive radiotherapy obliterates the plane between the posterior surface of the prostate and the overlying rectal wall, resulting in the higher incidence of rectal injury observed during SRP'''
***** '''SRP after brachytherapy is associated with greater difficulty and surgical complexity because of increased adhesions'''
**** '''Rectal injury rate: 0–28%'''
**** '''Management of rectal injury§'''
****# '''Two-layer closure (most commonly used)'''
****# '''Oversewing with the remnants of the neurovascular bundles'''
****# '''Use of omentoplasty'''
****# '''Colostomy'''
***** '''Some use bowel preparation before SRP'''
*** '''Some complications improved over time, others have not'''
***** '''Contemporary radiation approaches (EBRT and transperineal interstitial radiotherapy) associated with reduced pelvic fibrosis.'''
****** '''Early series reported complications in patients who had undergone pre-radiotherapy pelvic lymph node dissection (RT-PLND) and/or retropubic interstitial radiotherapy which frequently cause extensive pelvic fibrosis.'''
******* '''RT-PLND is now infrequently performed.'''
******* '''Retropubic interstitial radiotherapy has been abandoned.'''
***** '''Rate of rectal injury and anastomotic stricture has significantly reduced§'''
****** '''Rate of rectal injury before 2000: 0-28% vs. after 2000: 2-10%'''
****** '''Rate of anastomotic stricture before 2000: 7-28% vs. after 2000: 11-41%'''
***** '''Blood transfusion rates similar to the standard RP procedure'''
***** '''Urinary incontinence and ED remain problematic'''
* '''Nerve-sparing'''
**'''Can be performed in select patients based on preoperative characteristics, ease of dissection and intraoperative findings.'''
* Pelvic lymph node dissection
** SEER studies found that overall§ and cancer-specific§ survival were significantly improved in patients undergoing surgery + PLND after radiation compared to those undergoing surgery alone
*** Lymph node count independently predicted lower cancer-specific survival
**** After the 7th removed lymph node, the effect of cancer-specific survival became marginal
* Approach (open vs. robotic)
** Multi-institutional study (n=18) of 395 SRP (186 open vs. 209 robotic)
** Robotic surgery associated with significantly
*** Reduced blood loss and shorter hospital stay
*** Reduced anastomotic stricture rate (17% open vs. 8% robotic)
*** Improved urinary incontinence, defined as 3 or more pads per day (22% open vs. 32% robotic at 12 months)
*** Robotic approach independent predictor of continence preservation on multivariable analysis
** No significant difference in
*** Overall complications (36% open vs. 34 robotic)
*** Major complications (12% open vs. 17% robotic)
*** Rectal injury (3% open vs. 0.5% robotic)
** Gontero, Paolo, et al."Salvage radical prostatectomy for recurrent prostate cancer: morbidity and functional outcomes from a large multicenter series of open versus robotic approaches." The Journal of urology 202.4 (2019): 725-731.
* '''Concurrent ADT'''
** '''Inadequate data to support use of concurrent ADT'''§
** Data in salvage radiation after radical prostatectomy ('''GETUG-AFU 16''' see above) suggests that short-term ADT improves progression-free survival

====== Salvage cryotherapy ======
* An alternative to salvage radical prostatectomy with durable progression-free and overall survival, low perioperative morbidity and relatively low risk of urinary incontinence.
* Less morbid than salvage radical prostatectomy and may be performed in the outpatient setting.
* '''Complications include erectile dysfunction (very common),''' urinary obstruction, urethrorectal fistula, urethral sloughing, urethral stricture, rectal pain, scrotal edema, and hematuria
** Perioperative and postoperative complication frequencies have substantially declined with recent technical improvements in contemporary fourth generation devices, including enhanced urethral warmers and thermal controls to protect adjacent structures.

====== Salvage brachytherapy ======
* Evidence is lacking compared to salvage prostatectomy and salvage cryotherapy

====== Salvage High-Intensity Focused Ultrasound (HIFU) ======
* Although short- to intermediate-term follow-up has been demonstrated with HIFU, further studies are necessary to establish its place as a viable alternative in the radio-recurrent setting

===== ADT =====
* '''Most commonly used treatment for biochemical recurrence after RT'''
* '''Generally not curative in these patients'''
** '''Patients with biopsy-proven local disease, no evidence of distant metastatic disease, and substantial life expectancy should be counseled about salvage local therapy''' such as prostatectomy, radiation approaches, and cryotherapy.
* '''The exact timing of ADT after failure is unknown.'''
** '''The ideal management of PSA recurrence in patients at high risk for failure may be the initiation of intermittent ADT.'''
*** In a recent clinical trial, intermittent ADT was found to be noninferior compared to continuous therapy in patients with PSA levels greater than 3 ng/mL without evidence of metastatic disease. This came with the benefit of potential improvement in physical function, fatigue, urinary problems, hot flashes, libido, and erectile function (Crook et al, 2012).
*** See Hormonal Therapy Chapter Notes
* Considering the potential morbidity and cost of ADT, it is reasonable to start treatment in those patients at highest risk for distant failure
** '''PSA doubling times < 12 months is associated with benefit from ADT after biochemical recurrence following radiation therapy to the prostate.'''