Robotic Radical Prostatectomy in Patients with High-Risk Disease: A Review of Short-Term Outcomes from a High-Volume Center

Abstract

Purpose:

Patients with high-risk prostate cancer have historically been treated with multimodal therapy and considered poor candidates for minimally invasive surgery. We reviewed our experiences with robot-assisted radical prostatectomy (RARP) in patients with high-risk clinical features.

Materials and Methods:

Clinical database review identified high-risk patients undergoing RARP by two high-volume robotic surgeons. D'Amico's criteria for high-risk prostate cancer were utilized: prostate-specific antigen ≥20 ng/mL, clinical stage ≥T2c, or preoperative Gleason grade ≥8. About 148 patients were identified in the study group. Mean age at surgery was 60.9 years, and mean body mass index was 27.9. Mean estimated blood loss was 150 cc and the transfusion rate was 2.7%. Median hospital stay was 1 day and the rate of major complications (Clavien grade ≥3) was 3.4%.

Results:

Bilateral nerve preservation was feasible in 28.4%, and the rate of positive surgical margins was 20.9%. Final pathology demonstrated extra-capsular disease in 54.1% of patients and 12.3% had lymph node involvement. At 2 years of follow-up, 21.3% of patients had experienced biochemical recurrence or had persistent disease after treatment. Continence was 91.2% (1 pad or less) and total impotence (inability to masturbate) was 48.3%.

Conclusions:

RARP does not compromise oncologic or functional outcomes in patients with high-risk prostate cancer. Although long-term study is necessary to validate oncologic and functional outcomes, our data suggest that the presence of high-risk disease is not a contraindication to a minimally invasive approach for radical prostatectomy at experienced centers.

Introduction

Prostate-specific antigen (PSA) screening for prostate cancer (CaP) has significantly impacted the clinical and demographic characteristics of men with newly diagnosed tumors. Patients found to have CaP today are younger and healthier, and have a greater likelihood of having organ-confined disease.¹ This has created increasing debate regarding optimal treatment strategies in low-risk cancers, as patients living longer with the disease may be more cognizant of treatment-related morbidity. On the contrary, the outcomes and prognosis of patients with high-risk disease have not changed significantly in the PSA era.² D'Amico et al. first demonstrated poor oncologic outcomes after local therapy in patients with PSA >20 ng/mL, biopsy Gleason grade ≥8, and/or clinical stage T2c or higher.³ This, along with known higher rates of nodal disease and extracapsular extension in this cohort, made radiation therapy with androgen deprivation historically the treatment of choice. An increasing body of recent literature, however, has shown that radical prostatectomy monotherapy may yield similar oncologic and functional outcomes compared to radiation and androgen ablation in a high-risk setting.^4

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The treatment of CaP has also been affected by the emergence of minimally invasive techniques. Advances in laparoscopic and robotic technology along with sophisticated new ablative procedures have changed the way urologists approach patients with CaP. Specifically, robot-assisted radical prostatectomy (RARP) has become a common approach to localized disease due to low rates of transfusion, rapid convalescence, and adequate short-term functional and oncologic outcomes.¹⁰ The increasing availability of robotic technology to urologists has expanded the role and indications for RARP, including recent reports of this approach in a high-risk setting.^11

–15 We evaluated short-term functional and oncologic outcomes in patients with high-risk CaP undergoing RARP at our institution.

Methods

A clinical database review identified high-risk patients undergoing RARP (2003–2009) by two high-volume robotic surgeons. D'Amico's criteria for high-risk CaP were utilized to identify the study group: PSA ≥20 ng/mL, clinical stage ≥T2c, or preoperative Gleason grade ≥8. Patients meeting any one of these three criteria were included. All patients in the high-risk category were fully staged with bone scintigraphy and cross-sectional imaging if necessary. Patients with evidence of disseminated disease were not offered primary surgical therapy, and patients with positive frozen lymph nodes and/or aborted prostatectomy were also excluded. Standard template pelvic lymph node dissection was performed in all patients. All included patients had a minimum of 6 months of follow-up data. Preoperative potency was defined in the open group by chart record, indicating that the patient was at least able to masturbate, which corresponded to a Sexual Health Inventory in Men score of ≥17.

About 148 patients met the study criteria. Table 1 displays the clinical and operative characteristics of the study group. Mean age was 60.9 years and body mass index was 27.9. Over half of the cohort had at least one cardiovascular risk factor (diabetes, hypertension, coronary artery disease). Mean PSA was 11.3% and 75.7% had Gleason ≥8 on biopsy disease. Gleason grade alone determined high-risk status (70.9%) in a much higher percentage than PSA alone (14.9%). Median estimated blood loss was 150 cc and transfusion was required in 2.7%. Median hospital was 1 day and median days with catheter was six.

Table 1.

Perioperative Characteristics (n = 148)

Age at diagnosis (years)	60.9 (44–85)
BMI	27.9 (19.5–47.5)
Cardiovascular risk factors	81 (54%)
Preoperative PSA (ng/mL)	11.3 (0.7–44.0)
Biopsy Gleason 8 or higher	112 (75.7%)
Preoperative potency	100 (67.6%)
Median estimated blood loss (cc)	150 (25–1000)
Required blood transfusion	4 (2.7%)
Unilateral nerve spare	75 (51.4%)
Bilateral nerve spare	42 (28.8%)
Median days with Foley	6 (5–8)

BMI = body mass index.

Results

About 80.2% of all patients were able to undergo a partial or complete nerve-sparing procedure. Final pathologic results are listed in Table 2. About 41.8% of the cohort had Gleason ≥8, and 54% had extraprostatic extension. Lymph node positivity was noted in 12%. The rate of positive surgical margins was 21%.

Table 2.

Pathologic and Functional Outcomes (n = 148)

Gleason ≥8	61 (41.8)
≥pT3	79 (54.1)
LN positive	18 (12.3)
Median lymph node yield	15 (2–45)
Positive surgical margins	30 (20.5)
Disease recurrence	31 (21.3)
Received ADT/XRT	34 (23.3)
Continent (min. 6-month follow-up)	134 (91.8)
Completely impotent (min. 6-month follow-up)	68 (48.3)

Long-term oncologic and functional outcomes are reported in Table 2. Median follow-up was 18 months. Twenty-one percent of patients experienced biochemical recurrence or persistent disease after therapy. Twenty-three percent of patients underwent adjuvant therapy (XRT or ADT). With a minimum follow-up of 6 months for all patients, continence (defined as 1 pad or less) was 92% and potency was 52% (defined as ability to masturbate or greater).

Complications are listed in Table 3. Minor complications (Clavien 1–2, requiring only conservative management) were negligible (0.6%). About 3.4% of the study group developed a major complications (Clavien grade 3, requiring radiological or operative intervention). These consisted of lymphoceles requiring drainage (2), hematomas requiring drainage (2), and incisional hernia needing repair (1).

Table 3.

Complication Data (n = 148)

Minor (Clavien 1–2)	1 (0.6%)
Urethral stricture	1
Major (Clavien 3)	5 (3.4%)
Lymphocele	2
Hematoma/clot retention	2
Incisional hernia	1

Discussion

The optimal treatment for high-risk CaP, herein defined by PSA ≥20 ng/mL, clinical stage ≥T2c, or preoperative Gleason score ≥8, remains controversial. Several modalities, including radiation, androgen deprivation, and surgery, have all been applied in this setting.⁴ Oncologic outcomes after surgery have not significantly improved over the previous two decades.³ However, with a biochemical-free survival rate of 50% at 6 years and a downstaging rate of 20% for clinical T3 patients, radical prostatectomy remains a desirable option for many patients in this situation.^7,8 Only recently have urologists described the use of robot-assisted technology for treatment of high-risk patients.^11

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Rapid convalescence, lower blood loss, and decreased analgesic use are known advantages of robotic prostatectomy.¹⁰ Accordingly, our results showed excellent outcomes for hospital stay, estimated blood loss, need for transfusion, and time of indwelling catheter in the robotic cohort. The significance of these findings is underlined by the fact that our median body mass index was 28% and >50% had cardiovascular comorbidity. In addition, minor and major complications were minimal in our study, with no rectal injuries reported, a well-reported concern in patients with high-risk disease.

Our short-term follow-up precludes any definitive statements regarding oncologic efficacy with RARP in a high-risk setting. We observed similar final pathologic data, lymph node yield, and recurrence outcomes compared with similar series in the open high-risk literature. Further, recent data demonstrate robotic high-risk positive surgical margins rates of 23%–54%,^12,17 and open rates between 23% and 56%,^16,17 in line with our result of 21%. As such, we believe that the ability to achieve adequate oncologic outcomes in high-risk CaP is less a function of the modality employed as it is of patient selection and surgical experience.

Regarding functional outcomes, at a mean follow-up of 18 months, 92% of RARP were continent (defined as 1 pad or less). This is consistent with previous reports of continence in high-risk patients, which ranges from 79% to 100% and does not differ based on surgical approach.^5,11,18 Potency is much more difficult to objectively evaluate as there is significant variation in the literature as to the definition of potency after radical prostatectomy. Additionally, adjuvant therapy administration and the use of immediate postoperative phosphodiesterase-5 inhibitors further cloud the picture. Sixty-eight percent of our cohort indicated an ability to at least masturbate (Sexual Health Inventory in Men >/17), and postoperatively 52% of men reported the same at least 6 months after surgery. This coincides with the fact that 80% of the group was able to receive some sort of nerve-sparing procedure. This likely reflects individual surgeon practice rather than a perceived facility granted by robotic technology. However, the relative benefit of nerve-sparing in high-risk disease is debatable, and it should be utilized judiciously in this particular cohort.

Conclusion

RARP does not compromise oncologic or functional outcomes in patients with high-risk CaP. Although long-term study is necessary to validate oncologic and functional outcomes, our data suggest that the presence of high-risk disease is not a contraindication to a minimally invasive approach for radical prostatectomy in experienced centers.

Footnotes

Disclosure Statement

No competing financial interests exist.

Abbreviations Used

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