|Year : 2015 | Volume
| Issue : 1 | Page : 191-194
Comparison of primary radiation versus robotic surgery plus adjuvant radiation in high-risk prostate cancer: A single center experience
Prabhsimranjot Singh, Prashant Desai, Shruthi Arora, Anthony H Pham, A Gabriella Wernicke, Michael Smith, Dattatreyudu Nori, KS Clifford Chao, Bhupesh Parashar
Department of Radiation Oncology, Weill Cornell Medical Center, New York, NY 10065, USA
|Date of Web Publication||16-Apr-2015|
525E, 68th Street, Stich Radiation Center, NY, NY 10021
Source of Support: None, Conflict of Interest: None
Objective: The objective of this study was to compare robotic-prostatectomy plus adjuvant radiation therapy (RPRAT) versus primary RT for high-risk prostate cancer (HRPCa).
Materials and Methods: A retrospective chart review was performed for the HRPCa patients treated in our institution between 2000 and 2010. One hundred and twenty-three patients with high-risk disease were identified. The Chi-square test and Fisher's exact test were used to compare local control and distant failure rates between the two treatment modalities. For prostate-specific antigen comparisons between groups, Wilcoxon rank-sum test was used.
Results: The median follow-up was 49 months (range: 3-138 months). Local control, biochemical recurrence rate, distant metastasis, toxicity, and disease-free survival were similar in the two groups.
Conclusions: Primary RT is an excellent treatment option in patients with HRPCa, is equally effective and less expensive treatment compared with RPRAT. A prospective randomized study is required to guide treatment for patients with HRPCa.
Keywords: Prostate, radiation, robotic prostatectomy
|How to cite this article:|
Singh P, Desai P, Arora S, Pham AH, Wernicke A G, Smith M, Nori D, Clifford Chao K S, Parashar B. Comparison of primary radiation versus robotic surgery plus adjuvant radiation in high-risk prostate cancer: A single center experience. J Can Res Ther 2015;11:191-4
|How to cite this URL:|
Singh P, Desai P, Arora S, Pham AH, Wernicke A G, Smith M, Nori D, Clifford Chao K S, Parashar B. Comparison of primary radiation versus robotic surgery plus adjuvant radiation in high-risk prostate cancer: A single center experience. J Can Res Ther [serial online] 2015 [cited 2020 Aug 13];11:191-4. Available from: http://www.cancerjournal.net/text.asp?2015/11/1/191/139601
| > Introduction|| |
High-risk, locally advanced, prostate cancer has been associated with poor outcomes. The management of such patients is not entirely defined with surgery and radiation therapy (RT) plus hormones considered equivalent treatment options.  There are no phase III randomized trials comparing these two modalities, and all available data are retrospective in nature. The outcomes reported in the retrospective series were conflicting with some showing equivalent results, ,,,, while others show superiority of one modality over the other. ,,,, Robotic assisted radical prostatectomy (RARP) has been, in recent years, shown to provide similar outcomes to conventional surgery with decreased morbidity. , None of the series above, however, compare RARP with definitive radiation. There is randomized data to support the conclusion that for patients with high-risk features, RP with adjuvant radiation is superior to observation alone or salvage radiation (sRT) though the precise timing of RT was not addressed. ,, We, therefore, conducted this single center retrospective study in patients with high-risk prostate cancer (HRPCa) to compare RPART versus primary RT (with or without hormones).
| > Materials and methods|| |
This was a single-institution, retrospective study conducted after the Institutional Review Board approval. During the period of years between 2000 and 2010, 1828 patients diagnosed with prostate cancer were treated at our institution. Patients with HRPCa, defined here as having one of the following high-risk features: Gleason score 8-10, stage T3 (2002 American Joint Committee on Cancer [AJCC] staging system) and prostate-specific antigen (PSA) level ≥20, were selected. One hundred and twenty-three patients were determined to be eligible based on their high-risk features, respective treatment, and follow-up.
All patients received radiation. The patients were divided into two groups. One group (N = 83 [67%]) had patients who underwent RARP followed by adjuvant radiation (RPRAT). Adjuvant radiation was given to these high-risk patients for either (1) high-risk features demonstrated in surgical pathology or (2) when there is biochemical recurrence sRT The other group (N = 40 [37%]) HRPCa patients treated primarily with RT. Hormones were used in both groups as required by the disease status.
Staging was defined as per 2002 AJCC, tumor, lymph nodes, and metastasis system. Biochemical recurrence was defined as PSA levels >0.2 or three consecutive rises in PSA after treatment. Follow-up visits were arranged 2-4 weeks after completion of intensity-modulated RT (IMRT) and every 3-6 months for the first 2 years and annually thereafter. At every follow-up, a digital rectal examination and a serum PSA level were obtained at each visit. Patients alternated follow-up visits between their urologist and radiation oncologist.
The Chi-square test and Fisher's exact test were used to compare local control and distant failure rates between the two treatment modalities. For PSA comparisons between groups, Wilcoxon rank-sum test was used. The Kaplan-Meier method was used to estimate recurrence time distributions.
| > Results|| |
The median age was 65 (range: 46-87 years). Median follow-up was 49 months (range: 3-138 m). Patient characteristics are summarized in [Table 1]. The median Gleason score was 8 (range: 7-10), with median Gleason score distribution of 4 + 4, median pretreatment PSA was 6.9 (range: 2.62-38) and 8.7 (range: 3.1-401) for RPART and primary RT groups, respectively. Outcome of the entire cohort is shown in [Table 2], and comparison of RPART and primary RT is shown in [Table 3].
|Table 3: Comparative outcomes between primary RT and primary robotic surgery groups|
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Adjuvant radiation was delivered using IMRT (83%), three-dimensional/IMRT (2%), three-dimensional conformal (5%) with a median dose of 7020 cGy (range: 6040-7560 cGy). Median radiation therapy oncology group (RTOG) grade genitourinary toxicity was 0 (range: 0-2). Median post-RT PSA for entire cohort was 0.08 (range: 0.01-51.58).
Patients in primary RT group were older, (median age 70 vs. 61 in the RT and RPART groups, respectively). All patients were treated with IMRT except for two patients (5%) that were treated with IMRT plus prostate brachytherapy with palladium seeds. The median dose in IMRT group was 8100 cGy (range: 7560-14500 cGy [brachytherapy]).
Hormones were used in 64 (52%) patients, 33 (40%) in the RPART group and 32 (75%) in the primary RT alone group. Casodex was the most commonly used. In primary RT group, 23 (59%) patients in the received neoadjuvant hormones and 9 (23%) patients received hormones for the treatment of biochemical recurrence after radiation. In the surgical group, hormones were only used for the treatment of biochemical recurrence.
Biochemical recurrence rate was nonstatistically better in the RT group (38.6% vs. 27.3% in RPART and primary RT group (P = 0.26). Biochemical recurrence was proportionately related to pre-RT PSA (P < 0.019)-higher pre-RT PSA predicting higher PSA recurrence after treatment. However, post-RT PSA was not significantly different in those with and without recurrence (P = 0.26).
Local control was documented using clinical and radiological follow-ups, showing no evidence of tumor or recurrence. Local control was similar (95.8% vs. 95% in RPART and RT groups respectively, P = 0.84). Grade I and II RTOG toxicity was equivalent in both RPART and primary RT group [Table 4].
In our institution, cost of sRT using IMRT technique, for 39 fractions of 180 cGy each, to a total dose of 7020 cGy is $19,000 and for primary RT using 45 fractions to a total dose of 8100 cGy is $23,000. The average cost of an uncomplicated RARP at our hospital is $9500.
Average cost of treatment of a patient treated at our institution with RPART and primary RT is $28,500 versus $23,000, respectively. Average cost of hormones is $5400/year.
| > Discussion|| |
This is the first retrospective study showing equivalence of biochemical and local control between robotic prostatectomy followed by adjuvant radiation and primary radiation (±hormones) in HRPCa.
Traditionally, HRPCas were treated with primary radiation plus hormone therapy. ,, Outcomes with RT plus hormones were found to be superior to RT alone in terms of biochemical disease-free survival as well as overall survival. The length of hormones has been evaluated in randomized studies and with results showing benefit of adding hormones compared to no hormones, although a definite length of hormones is yet to be finalized. ,, In RTOG 9413, 1323 patients with HRPCa (defined as per Roach equation) were randomized in a 2 × 2 design to the whole pelvis RT (WPRT) versus prostate only RT (PORT) only RT and combined neoadjuvant plus concurrent hormone therapy versus adjuvant hormones therapy. With a median follow-up of 7 years for alive patients, progression-free survival (PFS) for WPRT + nonconformal RT was 62% versus 66% for PORT + neoadjuvant hormonal therapy (NAHT) versus WPRT + AHT 69% versus PORT + AHT 62%, and this difference was not statistically significant. There was no difference in overall survival (OS) between the groups  although the initial report had suggested that WPRT plus NHT was superior in terms of PFS. 
As per National Comprehensive Cancer Network guidelines, surgery alone or RT plus androgen deprivation therapy (ADT) can both be considered as equivalent treatment options for HRPCa.  RARP is being increasingly used for treatment of prostate cancer, although there is limited data regarding its long-term outcomes, especially in high-risk settings. A retrospective study on 1336 patients with intermediate risk and HRPCa patients comparing open RP (ORP) versus RARP showed the oncologic outcomes are similar between RALP and ORP.  In a recently published retrospective Surveillance, Epidemiology, and End Results study comparing of 5556 RARP and 7878 ORP cases from 2004 to 2009, RARP was associated with improved surgical margin status relative to ORP (13.6% vs. 18.3%; odds ratio: 0.70; 95% confidence interval: 0.66-0.75) for intermediate- and high-risk disease and less use of postprostatectomy ADT and RT.  Most series for RARP report similar positive margin rates with lower rates of blood loss and transfusions compared with traditional surgical approaches. ,
There have been several retrospective studies that compare outcomes between surgery (ORP) versus RT plus ADT with conflicting results. ,,,,,,,,, In a study published by Tewari et al.,  a retrospective cohort study using propensity score analysis was performed to calculate long-term survival in patients with prostate cancer with Gleason score 8 or greater that were treated with conservative therapy, RT and RP. Median overall survival for conservative therapy, radiation and radical prostatectomy was 5.2, 6.7 and 9.7 years, respectively. Median cancer specific survival was 7.8 years for conservative therapy and more than 14 years for RT and radical prostatectomy. The risk of cancer specific death following radical prostatectomy was 68% lower than for conservative treatment and 49% lower than for RT (P < 0.001 and 0.053, respectively). However, none of these studies compared RARP to primary RT.
A comprehensive comparative review of literature by prostate cancer results study group compared risk stratified patients by treatment options and long-term follow-up.  The study identified a lack of uniformity in reporting results among institutions and centers. A large number of studies have been conducted on the primary therapy of prostate cancer, but very few randomized controlled trials have been conducted. All studies involving treatment of localized prostate cancer published during 2000-2010 reviewed over 18,000 papers, and a further selection was made based follow-up, stratification into low-, intermediate-, and high-risk groups, clinical and pathological staging, and accepted standard definitions for PSA failure. Brachytherapy provides a statistically superior outcome in patients with low-risk disease; combination of external beam RT (EBRT) and brachytherapy was equivalent to brachytherapy alone in intermediate-risk disease. For high-risk patients, combination therapies involving EBRT and brachytherapy plus or minus ADT appeared superior to more localized treatments such as brachytherapy, surgery alone or EBRT.
In our study, we grouped the adjuvant RT and early sRT groups (in the surgical group) together for the purposes of outcome. We found that there is a higher rate of biochemical recurrence in the surgery group though this does not translate into local failure. Limitations of our study include the retrospective nature of the study as well as the fact that hormone use in the primary RT arm was not universal (75% received hormones). The other limitation is the relatively short duration of median follow-up (49 months), especially for analyzing the impact of treatment modality on diabetes mellitus and OS. When we compared the cost of the treatment at our institution, the surgery and it's postoperative cost followed by radiation for 39 treatments is costlier when compared to the treatment with primary radiation for 45 fractions ($28,500 vs. $23,000, respectively).
| > Conclusion|| |
Our study showed that primary RT (±hormones) is an excellent treatment option in patients with HRPCa, is equally effective and less expensive treatment compared to RPRAT. A randomized study is required to guide treatment for patients with HRPCa.
| > References|| |
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines In Oncology: Prostate Cancer version 2, 2013. Available from: http://www.NCCN.org
. [Last accessed on 2013 Apr 04].
Klein EA, Ciezki J, Kupelian PA, Mahadevan A. Outcomes for intermediate risk prostate cancer: Are there advantages for surgery, external radiation, or brachytherapy? Urol Oncol 2009;27:67-71.
D′Amico AV, Whittington R, Kaplan I, Beard C, Jiroutek M, Malkowicz SB, et al.
Equivalent biochemical failure-free survival after external beam radiation therapy or radical prostatectomy in patients with a pretreatment prostate-specific antigen of and gt; 4-20 ng/ml. Int J Radiat Oncol Biol Phys 1997;37:1053-8.
D′Amico AV, Whittington R, Malkowicz SB, Schultz D, Blank K, Broderick GA, et al.
Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA 1998;280:969-74.
Kupelian PA, Elshaikh M, Reddy CA, Zippe C, Klein EA. Comparison of the efficacy of local therapies for localized prostate cancer in the prostate-specific antigen era: A large single-institution experience with radical prostatectomy and external-beam radiotherapy. J Clin Oncol 2002;20:3376-85.
Boorjian SA, Karnes RJ, Viterbo R, Rangel LJ, Bergstralh EJ, Horwitz EM, et al.
Long-term survival after radical prostatectomy versus external-beam radiotherapy for patients with high-risk prostate cancer. Cancer 2011;117:2883-91.
Zelefsky MJ, Eastham JA, Cronin AM, Fuks Z, Zhang Z, Yamada Y, et al.
Metastasis after radical prostatectomy or external beam radiotherapy for patients with clinically localized prostate cancer: A comparison of clinical cohorts adjusted for case mix. J Clin Oncol 2010;28:1508-13.
Cooperberg MR, Vickers AJ, Broering JM, Carroll PR. Comparative risk-adjusted mortality outcomes after primary surgery, radiotherapy, or androgen-deprivation therapy for localized prostate cancer. Cancer 2011;117:2825.
Jeldres C, Suardi N, Perrotte P, Capitanio U, Walz J, Hutterer GC, et al.
Survival after radical prostatectomy and radiotherapy for prostate cancer: A population-based study. Can Urol Assoc J 2009;3:13-21.
Fletcher SG, Mills SE, Smolkin ME, Theodorescu D. Case-matched comparison of contemporary radiation therapy to surgery in patients with locally advanced prostate cancer. Int J Radiat Oncol Biol Phys 2006;66:1092-9.
Arcangeli G, Strigari L, Arcangeli S, Petrongari MG, Saracino B, Gomellini S, et al.
Retrospective comparison of external beam radiotherapy and radical prostatectomy in high-risk, clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 2009;75:975-82.
Novara G, Ficarra V, Mocellin S, Ahlering TE, Carroll PR, Graefen M, et al.
Systematic review and meta-analysis of studies reporting oncologic outcome after robot-assisted radical prostatectomy. Eur Urol 2012;62:382-404.
Novara G, Ficarra V, Rosen RC, Artibani W, Costello A, Eastham JA, et al.
Systematic review and meta-analysis of perioperative outcomes and complications after robot-assisted radical prostatectomy. Eur Urol 2012;62:431-52.
Bolla M, van Poppel H, Tombal B, Vekemans K, Da Pozzo L, de Reijke TM, et al.
Postoperative radiotherapy after radical prostatectomy for high-risk prostate cancer: Long-term results of a randomised controlled trial (EORTC trial 22911). Lancet 2012;380:2018-27.
Thompson IM, Tangen CM, Paradelo J, Lucia MS, Miller G, Troyer D, et al.
Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: Long-term follow-up of a randomized clinical trial. J Urol 2009;181:956-62.
Wiegel T, Bottke D, Steiner U, Siegmann A, Golz R, Störkel S, et al
. Phase III postoperative adjuvant radiotherapy after radical prostatectomy compared with radical prostatectomy alone in pT3 prostate cancer with postoperative undetectable prostate-specific antigen: ARO 96-02/AUO AP 09/95. J Clin Oncol 2009;27:2924-30.
Bolla M, Collette L, Blank L, Warde P, Dubois JB, Mirimanoff RO, et al.
Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): A phase III randomised trial. Lancet 2002;360:103-6.
Pilepich MV, Caplan R, Byhardt RW, Lawton CA, Gallagher MJ, Mesic JB, et al.
Phase III trial of androgen suppression using goserelin in unfavorable-prognosis carcinoma of the prostate treated with definitive radiotherapy: Report of Radiation Therapy Oncology Group Protocol 85-31. J Clin Oncol 1997;15:1013-21.
Hanks GE, Pajak TF, Porter A, Grignon D, Brereton H, Venkatesan V, et al.
Phase III trial of long-term adjuvant androgen deprivation after neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate: The Radiation Therapy Oncology Group Protocol 92-02. J Clin Oncol 2003;21:3972-8.
Lawton CA, DeSilvio M, Roach M 3 rd
, Uhl V, Kirsch R, Seider M, et al.
An update of the phase III trial comparing whole pelvic to prostate only radiotherapy and neoadjuvant to adjuvant total androgen suppression: Updated analysis of RTOG 94-13, with emphasis on unexpected hormone/radiation interactions. Int J Radiat Oncol Biol Phys 2007;69:646-55.
Bolla M, de Reijke TM, Van Tienhoven G, Van den Bergh AC, Oddens J, Poortmans PM, et al.
Duration of androgen suppression in the treatment of prostate cancer. N Engl J Med 2009;360:2516-27.
Roach M 3 rd
, DeSilvio M, Valicenti R, Grignon D, Asbell SO, Lawton C, et al.
Whole-pelvis, "mini-pelvis," or prostate-only external beam radiotherapy after neoadjuvant and concurrent hormonal therapy in patients treated in the Radiation Therapy Oncology Group 9413 trial. Int J Radiat Oncol Biol Phys 2006;66:647-53.
Ritch CR, You C, May AT, Herrell SD, Clark PE, Penson DF, et al.
Biochemical Recurrence-free Survival After Robotic-assisted Laparoscopic vs Open Radical Prostatectomy for Intermediate- and High-risk Prostate Cancer. Urology 2014;83:1309-15.
Hu JC, Gandaglia G, Karakiewicz PI, Nguyen PL, Trinh QD, Shih YC, et al.
Comparative Effectiveness of Robot-assisted versus Open Radical Prostatectomy Cancer Control. Eur Urol 2014; Feb 19. pii: S0302-2838 (14) 00134-1.
Tewari A, Divine G, Chang P, Shemtov MM, Milowsky M, Nanus D, et al.
Long-term survival in men with high grade prostate cancer: A comparison between conservative treatment, radiation therapy and radical prostatectomy - a propensity scoring approach. J Urol 2007;177:911-5.
Grimm P, Billiet I, Bostwick D, Dicker AP, Frank S, Immerzeel J, et al.
Comparative analysis of prostate-specific antigen free survival outcomes for patients with low, intermediate and high risk prostate cancer treatment by radical therapy. Results from the Prostate Cancer Results Study Group. BJU Int 2012;109 Suppl 1:22-9.
[Table 1], [Table 2], [Table 3], [Table 4]