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== Radical prostatectomy (RP) == * The first treatment used for prostate cancer and has been performed for almost 150 years * Recent innovations that have led to wider use include (3): *# Development of the anatomic radical retropubic prostatectomy, which allows the dissection to be performed with good visualization and preservation of the cavernosal nerves responsible for erectile function and preservation of the external sphincter muscle that yields urinary continence rates in excess of 90%. *# Development of extended ultrasound-guided biopsy regimens, performed under local anesthesia as an office procedure *# Widespread use of PSA testing, which has led to the great majority of patients being diagnosed with clinically localized disease. * '''Advantages of RP (3):''' *# '''Possibility of cure with minimal collateral damage to surrounding tissues''' *# '''Accurate tumor staging by pathologic examination of the surgical specimen''' *# '''Treatment failure more readily identified, allowing for potentially curative salvage radiotherapy to be undertaken''' * '''Disadvantages of RP (3):''' *# '''Necessary hospitalization and recovery period''' *# '''Possibility of incomplete tumor resection, if the operation is not performed properly or if the tumor is not contained within the prostate gland''' *# '''Treatment-related morbidity (risk of erectile dysfunction and urinary incontinence)''' * '''<span style="color:#ff0000">Surgical approaches</span>''' ** '''<span style="color:#ff0000">Open</span>''' *** See [[Open Radical Prostatectomy]] Chapter Notes *** '''<span style="color:#ff0000">Approaches: perineal vs. retropubic</span>''' **** '''<span style="color:#ff0000">Perineal</span>''' ***** '''<span style="color:#ff0000">Advantages (2):</span>''' *****# '''<span style="color:#ff0000">Reduced blood loss</span>''' than the retropubic approach *****# '''<span style="color:#ff0000">Shorter operative time</span>''' than the retropubic approach ***** '''<span style="color:#ff0000">Disadvantages (3):</span>''' *****# '''<span style="color:#ff0000">No access for a pelvic lymph node dissection</span>''' *****# '''<span style="color:#ff0000">Higher rate of rectal injury</span>''' *****# '''<span style="color:#ff0000">Occasional post-operative fecal incontinence that does not occur commonly with other approaches</span>''' **** '''<span style="color:#ff0000">Retropubic''' ***** '''<span style="color:#ff0000">Advantages/disadvantages opposite of perineal and surgeons more familiar with surgical anatomy''' ** '''<span style="color:#ff0000">Laparoscopic</span>''' *** Can be performed through a transperitoneal or extraperitoneal approach **** Transperitoneal approach facilitates the lymphadenectomy but carries a higher risk of intestinal and vascular injury, urinary ascites, and post-operative ileus and intestinal obstruction. **** Extraperitoneal approach poses logistical limitations, especially with the use of a robot. *** '''<span style="color:#ff0000">Robot-assisted</span>''' **** '''See [https://pubmed.ncbi.nlm.nih.gov/19646130/ BJUI Surgical Atlas] for details and figures''' **** '''<span style="color:#ff00ff">RCT comparing open to robotic RP (2018)</span>''' ***** Population: 326 men with newly diagnosed clinically localised prostate cancer ***** Randomized to robot-assisted laparoscopic prostatectomy or open radical retropubic prostatectomy ***** Primary outcomes: urinary, sexual, and oncologic at 24 months ***** '''Results:''' ****** '''Urinary: no difference''' ****** '''Sexual: no difference''' ****** '''Oncologic: biochemical recurrence significantly worse in open RP''' (absolute risk difference 6%) ***** '''Author’s advise caution in interpreting the oncological outcomes''' of our study because of the absence of standardisation in postoperative management between the two trial groups and the use of additional cancer treatments. Clinicians and patients should view the benefits of a robotic approach as being largely related to its minimally invasive nature. ***** [https://www.ncbi.nlm.nih.gov/pubmed/30017351 Coughlin, Geoffrey D., et al.] "Robot-assisted laparoscopic prostatectomy versus open radical retropubic prostatectomy: 24-month outcomes from a randomised controlled study." The Lancet Oncology 19.8 (2018): 1051-1060. **** '''Health Quality Ontario''' ***** '''No high-quality evidence that robot-assisted RP improves functional and oncological outcomes compared with open and laparoscopic approaches. However, compared with open RP, the costs of using the robotic system are relatively large while the health benefits are relatively small.''' ***** [https://www.ncbi.nlm.nih.gov/pubmed/28744334 Health Quality Ontario.] "Robotic surgical system for radical prostatectomy: a health technology assessment." Ontario health technology assessment series 17.11 (2017): 1. ** '''<span style="color:#ff00ff">Antibiotic prophylaxis at the time of catheter removal after radical prostatectomy</span>''' *** Population: 167 patients undergoing radical prostatectomy *** Randomized to antibiotic prophylaxis (2 doses of oral ciprofloxacin prior to urinary catheter removal) vs. control (no antibiotics given prior to urinary catheter removal). *** Primary outcome: development of symptomatic UTI within 6 weeks after catheter removal *** Results: **** No significant difference between prophylaxis (4%) vs. control (6%) *** [https://pubmed.ncbi.nlm.nih.gov/30558984/ Berrondo, Claudia, et al.] "Antibiotic prophylaxis at the time of catheter removal after radical prostatectomy: A prospective randomized clinical trial." ''Urologic Oncology: Seminars and Original Investigations''. Vol. 37. No. 3. Elsevier, 2019. * '''Selection of patients''' ** The generally accepted upper age limit for RP is ≈76 years ** The role of nerve-sparing surgery is questionable when there is: **# Extensive cancer in the biopsy specimens **# Palpable extraprostatic tumor extension **# Serum PSA level > 10 ng/mL **# Biopsy Gleason score > 7 **# Poor-quality erections preoperatively **# Current and future lack of a sexual relationship **# Other medical conditions that may adversely affect erections (e.g., diabetes mellitus, hypertension, psychiatric diseases, neurologic diseases, or medications that produce erectile dysfunction) * '''Nerve-sparing[https://pubmed.ncbi.nlm.nih.gov/35536144/]''' ** '''Preservation of the neurovascular bundles during radical prostatectomy (nerve-sparing), when oncologically appropriate, should be performed.''' ** '''Decision to perform nerve-sparing is frequently multifactorial, and may include PSA, DRE, biopsy findings (grade, tumor volume, and location), MRI findings, as well as the patient’s baseline erectile function and stated prioritization of sexual function.''' *** MRI (i.e. absence of extracapsular extension) should not be used in isolation to determine nerve-sparing, as the ability of MRI to predict extracapsular extension, particularly when microscopic, is suboptimal. ** No RCTs comparing nerve-sparing versus non-nerve sparing radical prostatectomy *** Observational studies have found that nerve-sparing is ****Consistently associated with a lower likelihood of postoperative erectile dysfunction ****Variously but favorably been associated with improved urinary continence after surgery ****Not associated with significantly increased risks of positive surgical margins or biochemical recurrence * '''Pelvic lymphadenectomy[https://pubmed.ncbi.nlm.nih.gov/35536144/]''' ** '''Advantages''' ***'''Provides staging information which may guide future management''' ****No consistent benefit in biochemical recurrence, metastasis-free, cancer-specific, and overall survival *****Two recent trials randomized patients undergoing radical prostatectomy to limited versus extended PLND. In both trials, no statistically significant difference in subsequent biochemical recurrence-free survival was identified between the treatment arms. ******One of the trials did note improved biochemical recurrence-free survival with extended lymph node dissection in an exploratory subgroup analysis of patients with Grade Group 3 to 5 tumors. **'''Disadvantages''' ***Increased operating time ***Increased risk of blood loss ***Increased risk of lymphocele **'''<span style="color:#ff0000">Nomograms should be used to select patients for lymphadenectomy</span>''' ***Potential benefit of identifying lymph node positive disease should be balanced with the risk of complications ***'''<span style="color:#ff0000">No threshold provided</span>,''' should be based on shared-decision making ****2023 NCCN guidelines no longer use threshold of ≥2% (previous versions did). ***** 2023 NCCN guidelines describe that published thresholds range from 2% to 7%. ****See [https://www.mskcc.org/nomograms/prostate/pre_op Memorial Sloan Keterring Cancer Center Pre-Radical Prosatectomy Calculator] **If performed, should be an extended dissection (obturator fossa, external iliac, and internal iliac), which improves staging accuracy compared to limited dissection **'''If suspicious regional nodes are encountered intraoperatively, radical prostatectomy should be completed''' ***Retrospective studies have reported a benefit to completion of radical prostatectomy among patients found to have positive nodes compared to patients whose surgery was aborted and who were then treated with ADT alone. ** '''<span style="color:#ff0000">Positive lymph nodes (pN1)</span>''' ***See [[Prostate Cancer: Management of Locally Advanced Prostate Cancer|Management of Locally Advanced Prostate Cancer Chapter Notes]] *'''<span style="color:#ff0000">Complications</span>''' ** '''Intra-operative''' **'''Early post-operative''' **'''Late post-operative''' ***'''Open''' **** '''See [[Open Radical Prostatectomy]] Chapter Notes''' *** '''Robotic''' **** Incisional hernia ***** Transverse skin incision for camera port placement and transverse fascial incision for prostate specimen extraction has been associated with a decrease in the risk of incisional hernia from 5.4% to 0.4%. ***** Fascial closure is required for non-bladed trocar sizes of 10 mm or more. ***** No evidence that specimen extraction above versus below the umbilicus affects the likelihood of incisional hernia. ***** Squeezing around the specimen through a minimally-sized incision increases the risk of tearing the fascia and subsequent incisional hernia formation. ***** Some evidence that interrupted versus continuous closure may result in lower risk of incisional hernia, particularly for midline hand-assisted approaches. ***'''Urinary incontinence''' ****Leakage requiring pads[https://evidence.nejm.org/doi/full/10.1056/EVIDoa2300018] *****Over 7-12 years: 18-24% with prostatectomy vs. 9-11% active monitoring vs. 3-8% radiotherapy ***'''Erectile dysfunction''' ****Erections sufficient for intercourse at 7 years[https://evidence.nejm.org/doi/full/10.1056/EVIDoa2300018]: 18% prostatectomy vs. 30% active monitoring vs. 27% radiotherapy; all converge to low levels of potency by year 12 ***'''Vesicourethral Anastomotic Stenosis[https://pubmed.ncbi.nlm.nih.gov/33324673/][https://pubmed.ncbi.nlm.nih.gov/37079876/]''' ****Incidence *****1.3-4.8% *****Less common with robotic compared to open surgery *****More common after salvage RP (22-40%) ****Generally occurs within first 3-6 months after surgery *****Incidence significantly decreases 2 years after surgery ****Diagnosis and Evaluation *****History and physical exam ******History *******Clinical presentation generally includes voiding lower urinary tract symptoms (weak stream and hesitancy) *****Labs ******PSA *******Should be ordered to rule out recurrence *****Imaging ******Retrograde urethrogram ******Voiding cystourethrogram *****Other ******Flow assessment with post-void residual ******Cystoscopy ****Management *****Endoscopic procedures *****Surgical reconstruction * '''Cancer control''' ** PSA is expected to be undetectable 2 months after a successful RP[https://pubmed.ncbi.nlm.nih.gov/2468795/] **'''RP can provide long-term cancer control in ≈50% of highly selected men with high-risk or locally advanced disease''' ** '''Biochemical recurrence is frequently used as an intermediate end point for treatment outcomes; however, not all patients with biochemical recurrence ultimately develop metastases or die of prostate cancer (See Pound et al.)''' ** Independent clinical prognostic factors [for biochemical recurrence] are tumor pathology, Gleason score, pre-operative PSA level, and treatment. *** Adverse prognostic features include: **** Non–organ-confined disease **** Lymphovascular space invasion **** Extraprostatic extension **** Positive surgical margins **** Seminal vesicle invasion **** Lymph node metastases ** Nomograms *** Partin tables **** Preoperative clinical and pathologic parameters (PSA, clinical stage, Gleason score) are used to predict the pathologic stage in patients undergoing radical prostatectomy *** Kattan nomogram **** Preoperative clinical and pathologic parameters (PSA, clinical stage, Gleason score) are used to predict the risk of biochemical recurrence after prostatectomy **** [https://www.ncbi.nlm.nih.gov/pubmed/9605647 Kattan, Michael W., et al.] "A preoperative nomogram for disease recurrence following radical prostatectomy for prostate cancer." JNCI: Journal of the National Cancer Institute 90.10 (1998): 766-771. *** CAPRA score **** Developed to predict biochemical-recurrence after radical prostatectomy **** Based on 5 criteria: ***** Age ***** PSA ***** Clinical stage ***** Gleason score ***** % of positive biopsy cores that were positive for cancer **** Score ranges from 0-10 **** [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948569/ Cooperberg, Matthew R., et al.] "The University of California, San Francisco Cancer of the Prostate Risk Assessment score: a straightforward and reliable preoperative predictor of disease recurrence after radical prostatectomy." ''The Journal of urology'' 173.6 (2005): 1938-1942. ** '''In rare instances with high-grade or neuroendocrine tumors that do not produce much PSA, there can be palpable evidence of recurrence despite an undetectable PSA level, indicating a role for DRE in monitoring of patients.''' * '''<span style="color:#ff0000">Neoadjuvant ADT</span>''' ** '''<span style="color:#ff0000">May be associated with clinical stage downstaging and lower rate of positive margins; however, not associated with pathological downstaging, lymph node metastases rates, cancer- specific or overall survival</span>''' *** '''Neoadjuvant hormone therapy does not enhance the resectability of prostate cancer and often increases the difficulty of performing nerve-sparing surgery (Soloway et al, 2002).''' ** '''May have benefit in patients with high-risk disease''' *** Klotz, L. H., et al. "Long-term followup of a randomized trial of 0 versus 3 months of neoadjuvant androgen ablation before radical prostatectomy." The Journal of urology 170.3 (2003): 791-794. *** Aus, G., et al. "Three‐month neoadjuvant hormonal therapy before radical prostatectomy: a 7‐year follow‐up of a randomized controlled trial." BJU international 90.6 (2002): 561-566. * '''Neoadjuvant chemotherapy''' ** '''Rarely produces pathologic complete responses''' *Minimal or no residual cancer ** Approximately 0.2-2% of patients undergoing radical prostatectomy for a pre-surgical pathologic diagnosis of prostate cancer have been found to have minimal or no residual cancer on prostatectomy specimen[https://pubmed.ncbi.nlm.nih.gov/15217431/][https://pubmed.ncbi.nlm.nih.gov/9042283/]
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